WO2008086182A2 - Use of gene signatures to design novel cancer treatment regimens - Google Patents

Use of gene signatures to design novel cancer treatment regimens Download PDF

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Publication number
WO2008086182A2
WO2008086182A2 PCT/US2008/050237 US2008050237W WO2008086182A2 WO 2008086182 A2 WO2008086182 A2 WO 2008086182A2 US 2008050237 W US2008050237 W US 2008050237W WO 2008086182 A2 WO2008086182 A2 WO 2008086182A2
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cell
cancer
cells
biocarta
perturbations
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PCT/US2008/050237
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French (fr)
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WO2008086182A3 (en
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Craig T. Jordan
Monica L. Guzman
Duane C. Hassane
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University Of Rochester
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
    • G16B25/10—Gene or protein expression profiling; Expression-ratio estimation or normalisation
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • G16B40/30—Unsupervised data analysis
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding

Definitions

  • AML treatment involves the use of broadly toxic agents including anthracyclines (e.g. idarubicin and daunorubicin) and nucleoside analogs (e.g. cytarabine; Ara-C), which interfere with DNA replication and synthesis.
  • anthracyclines e.g. idarubicin and daunorubicin
  • nucleoside analogs e.g. cytarabine; Ara-C
  • AML-SCs are largely refractory to current chemotherapeutics (Guzman, MX. & Jordan, CT. (2004) Cancer Control 11, 97-104; Guzman, MX. et al. (2002) Proc Natl Acad Sci USA 99, 16220-5), thus representing a likely reservoir of malignant cells in disease relapse. Therefore, new treatments that target AML-SCs are needed as are methods of identifying said treatments.
  • Figure IA shows the flow cytometric profiles of a representative AML specimen treated with a sublethal concentration of PTL (2.5 ⁇ M), ciclopirox (20 ⁇ M), or the combination of both drugs (ciclo + PTL) for 24 hours. Post-treatment viability was determined for CD34+ cells using flow cytometry (annexin V and 7-AAD). 6.
  • Figure 2A shows viability relative to untreated control for CD34+CD38- primitive cells treated 1 ⁇ M or 2 ⁇ M celastrol. Viability indicates % of cells that are
  • Figure 2C shows flow cytometric analyses of a representative AML specimen gated on CD34+CD38-CD123+ cells. Cells were treated with vehicle, 5 ⁇ M wortmannin, 2.5 ⁇ M PTL, or 5 ⁇ M wortmannin + 2.5 ⁇ M PTL. Annexin V (x-axis) is shown compared to 7-AAD (y-axis).
  • Figure 2E shows the results of methylcellulose colony assays of cells treated with
  • Figure 3 A shows flow cytometric profiles of CD34+CD38- cells untreated treated with 5 ⁇ M troglitazone, 20 ⁇ M prochlorperazine, or the combination of both for 24 hours. Annexin V (x-axis) is shown compared to 7-AAD (y-axis). 14. Fig.
  • data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point "10" and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
  • Primers are a subset of probes which are capable of supporting some type of enzymatic manipulation and which can hybridize with a target nucleic acid such that the enzymatic manipulation can occur.
  • a primer can be made from any combination of nucleotides or nucleotide derivatives or analogs available in the art which do not interfere with the enzymatic manipulation.
  • Probes are molecules capable of interacting with a target nucleic acid, typically in a sequence specific manner, for example through hybridization. The hybridization of nucleic acids is well understood in the art and discussed herein. Typically a probe can be made from any combination of nucleotides or nucleotide derivatives or analogs available in the art.
  • a “decrease” can refer to any change that results in a smaller amount of AML cell activity.
  • a “decrease” can refer to a reduction in an activity.
  • a decrease can refer to a change in the symptoms of a disorder such that the symptoms are less than previously observed.
  • a decrease can also refer to a change in the rate or progression of a disease or condition.
  • a complete inhibition or slowed rate of growth or metastisis of a tumor would be a decrease. It is understood that a decrease in the amount in AML cell activity can include but is not limited to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% decrease.
  • a substance is also understood to decrease the genetic output of a gene when the genetic output of the gene product with the substance is less relative to the output of the gene product without the substance. Also for example, a decrease can be a change in the symptoms of a disorder such that the symptoms are less than previously observed.
  • An “increase” can refer to any change that results in a larger amount of an AML cell activity.
  • an increase in the amount of an AML cell activity can include but is not limited to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% increase.
  • “Inhibit,” “inhibiting,” and “inhibition” mean to decrease an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This may also include, for example, a 10% reduction in the AML cell activity, response, condition, or disease (such as AML) as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels.
  • perturbations refers to any manipulation to a cell that results in a change in the molecular abundances of the genes and proteins of the cell.
  • a perturbation can be but is not limited to pharmaceutical agents, chemical agents, environmental conditions such as stress, gamma irradiaition, UV-irradiation, mutagens, and gene therapy (including but not limted to vectors designed to overexpress a gene, introduce a exogenous gene, or reduce the expression of an overexpressed gene).
  • perturbations refer pharmaceutical agents or manipulations used in the course of treatment for a disease. 29.
  • “Treatment,” “treat,” or “treating” mean a method of reducing the effects of a disease or condition.
  • Treatment can also refer to a method of reducing the disease or condition itself rather than just the symptoms.
  • the treatment can be any reduction from native levels and can be but is not limited to the complete ablation of the disease, condition, or the symptoms of the disease or condition. Therefore, in the disclosed methods, treatment” can refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of an established disease or the disease progression or in an assay for a disease progression, such as the acute myeloid leukemia (AML) assays described herein.
  • AML acute myeloid leukemia
  • a disclosed method for reducing the effects of AML is considered to be a treatment if there is a 10% reduction in one or more symptoms of the disease in a subject with the disease when compared to native levels in the same subject or control subjects.
  • the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels.
  • treatment does not necessarily refer to a cure of the disease or condition, but an improvement in the outlook of a disease or condition.
  • tissue samples can be obtained by any means known in the art including invasive and non-invasive techniques. It is also understood that methods of measurement can be direct or indirect. Examples of methods of obtaining or measuring a tissue sample can include but are not limited to tissue biopsy, tissue lavage, aspiration, tissue swab, spinal tap, magnetic resonance imaging (MRI), Computed Tomography (CT) scan, Positron Emission Tomography (PET) scan, and X-ray (with and without contrast media). 31.
  • various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon.
  • identifying a treatment comprising one or more perturbations having anti-cancer activity comprising a) obtaining one or more first cells, b) obtaining one or more second cells, wherein the second cell has been subject to a modification to differ from the first cell, c) performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d) performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e) performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f) identifying perturbations that modulate the molecular abundance of one or more molecule sets, g) selecting combinations of perturbations wherein each perturbation modulates at least one molecule set arising from the comparison of the first and second cells, and h) testing whether the combination of perturbations recapitulates the desired biological outcome arising from the comparison of the first and second cells.
  • first cell and second cell similar with the exception of the modification to the second cell.
  • modification can refer to any manipulation of a cell that results in a change in molecular abundances of the second cell relative to the first cell.
  • modification can include but is not limited to contacting a cell with an agent wherein the agent results in a change in the molecular abundance of the cell relative to the first cell, subjecting the cell to a mutagen (including but not limited to chemical mutagens, UV light, irradiation), and genetic manipulations such as the overexpression or repression of one or more genes by any known method including the use of genes or proteins that block transcription, translation, and compete for resources available to a cell.
  • mutagen including but not limited to chemical mutagens, UV light, irradiation
  • genetic manipulations such as the overexpression or repression of one or more genes by any known method including the use of genes or proteins that block transcription, translation, and compete for resources available to a cell.
  • modification in one aspect can mean subjecting the second cell to a treatment, for example, a treatment for cancer.
  • a treatment for example, a treatment for cancer.
  • methods for identifying a treatment comprising one or more perturbations having anti-cancer activity comprising a) obtaining one or more first cells, b) obtaining one or more second cells, wherein the second cell is a mutated cell, and wherein the mutated cell arises from a cell similar to the first cell, c) performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d) performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e) performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f) identifying perturbations that modulate the molecular abundance of one or more
  • the first and second cell can comprise any cell from which a comparison can be made.
  • the first and/or second cell can comprise a cell or cells derived from a cell line.
  • the cell line can be a cancer cell line.
  • the first and/or second cell can comprise a cell obtained from a subject such as a primary cell.
  • the first and/or second cell can be a "normal" cell derived or obtained from any mammalian tissue or can be a cell with a naturally occurring mutation or cancerous cell.
  • the first and/or second cell can be a cancerous cell.
  • a cancerous first or second cell could be derived from any cancer type.
  • the first and/or second cell is derived from a cancer selected from the group consisting of lymphoma, B cell lymphoma, T cell lymphoma, mycosis fungoides, Hodgkin's Disease, leukemias, myeloid leukemia, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of head and neck, lung cancers such as small cell lung cancer and non-small cell lung cancer, neuroblastoma/glioblastoma, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, liver cancer, melanoma, squamous cell carcinomas of the mouth, throat, larynx, and lung, gastric cancer, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial cancer, bone cancers, renal cancer, bladder cancer, genitourinary cancer, esophageal
  • Stem cells have three distinctive properties: self-renewal (i.e., at cell division, one or both daughter cells retain the same biologic properties as the parent cell), the capability to develop into multiple lineages, and the potential to proliferate extensively.
  • self-renewal i.e., at cell division, one or both daughter cells retain the same biologic properties as the parent cell
  • the combination of these three properties makes stem cells unique.
  • the attribute of self-renewal is especially notable, because its subversion is highly relevant to oncogenesis and malignancy. Aberrantly increased self-renewal, in combination with the intrinsic growth potential of stem cells, may account for much of what is considered a malignant phenotype.
  • tumor-initiating cells have been identified in cancers of the hematopoietic system, brain, and breast. These cells have the capacity for self-renewal, the potential to develop into any cell in the overall tumor population, and the proliferative ability to drive continued expansion of the population of malignant cells. Accordingly, the properties of tumor-initiating cells closely parallel the three features that define normal stem cells. Malignant cells with these functional properties have been termed "cancer stem cells"
  • cancer stem cells are essential for its growth.
  • the concept of cancer stem cells can, however, vary in different contexts.
  • cancer stem cells can be the source of all the malignant cells in a primary tumor, they can compose the small reservoir of drug-resistant cells that are responsible for relapse after a chemotherapy induced remission, or they can give rise to distant metastases.
  • the biologic features of cancer stem cells in each of these instances may differ, suggesting that the acquisition of features associated with tumor progression, such as genetic instability and drug resistance, will also be associated with cancer stem cells. 39.
  • CML stem cells chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML), and they have been implicated in acute lymphoblastic leukemia (ALL).
  • CML stem cells have a well-described stem-cell phenotype and a quiescent cell-cycle status.
  • AML stem cells are mostly quiescent, suggesting that conventional antiproliferative cytotoxic regimens are unlikely to be effective against them.
  • AML stem cells have surface markers, such as the interleukin-3-receptor a chain, that are not present on normal stem cells. These markers are useful for antibody- based or other related therapeutic regimens.
  • composition having anti-cancer activity wherein the first and/or second cells are leukemia stem cells. Also contemplated herein are methods of identifying a composition having anti-cancer activity comprising AML or CML stem cells.
  • compositions as well as compositions identified through the disclosed methods can be used to treat any disease where uncontrolled cellular proliferation occurs such as cancers, as well as any of the methods described herein can be used for any uncontrolled cellular proliferation disesease, such as cancer can also be used.
  • lymphomas Hodgkins and non- Hodgkins(including but not limited to: diffuse large cell, Burkitt's, mantle cell, follicular, and T cell)
  • leukemias including but not limited to Acute myelogenous leukemia, Acute lymphoblastic leukemia, Chronic myelogenous leukemia (chronic, accelerated, and blast crisis), Chronic lymphocytic leukemia, Myelodysplastic syndromes, Myeloproliferative diseases/syndromes, Multiple myeloma, carcinomas,
  • a representative but non-limiting list of cancers that the disclosed compositions can be used to treat as well as any of the methods described herein can be used for any uncontrolled cellular proliferation disease, such as cancer can also be used is the following: lymphoma, B cell lymphoma, T cell lymphoma, mycosis fungoides, Hodgkin's Disease, non-hodgkin's lymphomas, myeloid leukemia (acute and chronic), lymphoid leukemia (acute and chronic), multiple myeloma, neuroblastoma, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of head and neck, lung cancers such as small cell lung cancer and non-small cell lung cancer, neuroblastoma/glioblastoma, ovarian cancer, skin cancer, liver cancer, melanoma, squamous cell carcinomas of the mouth, throat, larynx, and lung, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial
  • AML Acute myeloid leukemia
  • AML Acute myelogenous leukemia
  • LSCs leukemic stem cells
  • HSCs normal hematopoietic stem cells
  • LSCs like HSCs
  • HSCs are largely quiescent and display heterogeneity within the stem cell compartment.
  • NF-KB nuclear factor KB
  • IRF-I interferon regulatory factor 1
  • DAP death-associated protein
  • molecular abundance techniques can include but are not limited to gene expression arrays and protein expression arrays.
  • a genome tiling array which can be used in conjunction with for example --ChIP on chip — to capture epigenetic differences associated with a biological state (such as drug treated vs. untreated).
  • other methods can be used, for example, differential histone acetylation or differential DNA methylation.
  • the differential genetic analysis technique can include gene set analysis. Such analysis allows for the identification of drug combinations determined by looking for epigenetic changes.
  • the disclosed molecular abundance techniques include but are not limited to Northern analysis, RNAse protection assay, PCR, QPCR, RT-PCR, RT-PCR arrays, microRNA arrays, exon arrays, genome microarray, low density PCR array, oligo array, SAGE, high throughput sequencing, protein microarray, antibody-based or protein activity-based assays and mass spectrometry.
  • RNAse protection assay PCR
  • QPCR RT-PCR
  • RT-PCR arrays microRNA arrays
  • exon arrays genome microarray
  • low density PCR array low density PCR array
  • oligo array oligo array
  • SAGE high throughput sequencing
  • protein microarray antibody-based or protein activity-based assays and mass spectrometry.
  • molecule sets can refer to protein sets or gene sets. It is understood and herein contemplated that a molecule set can consist of any number of molecules greater than or equal to two.
  • the specific molecules in a molecule set can share a known biological relationship such as "heat shock proteins” as defined by wet bench work or by searching the literature.
  • the specific molecules in the molecule set can share a computationally defined relationship, for example, genes predicted by a computational algorithm to commonly possess NfkB binding sites in their promoter regions.
  • a molecule set can consist of a group of molecules shown to have a mathematical relationship by for example hierarchical clustering or k-means clustering. It is further understood that a molecule set can consist of a group of molecules arising from microarray analysis, for example, the top N genes upregulated or downregulated by "things”: e.g. a drug or siRNA knockdown or a xenobiotic.
  • things e.g. a drug or siRNA knockdown or a xenobiotic.
  • the Connectivity Map it can be said there are 453 gene sets consisting of the top 100 genes upregulated in each instance and an additional 453 gene sets consisting of the top 100 genes downregulated in each instance.
  • gene sets can include but are not limited to the following:
  • TRAFl 41bbPathway TNF-type receptor 4- IBB is bound by TRAFl to activate the MAP kinase pathway in activated T cells.
  • ACE2 Angiotensin-converting enzyme 2
  • CYP2E1 achPathway Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway.
  • RAPSN TERT MUSK PTK2 CHRNG RAPSN TERT MUSK PTK2 CHRNG
  • AKTl PIK3CA PIK3R1 BAD PTK2B YWHAH SRC CHRNBl FOXO3ATNFSF6 actinYPathway The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility.
  • GPCRs G-protein coupled receptors
  • AHSP Alpha-hemoglobin stabilizing protein
  • HBB FECH aifPathway BLACK ADPRT PDCD8 BCL2L1 CYCS akapl3Pathway A-kinase anchor protein 13 (AKAP 13) localizes protein kinase A holoenzyme and is a nucleotide exchange factor for Rho/Rac.
  • AKAP 13 A-kinase anchor protein 13
  • PRKAR2B EDG2 AKAP 13 ARHA EDG7 akap96Pathway BioCarta CDC2 DDX5 PRKACG PRKAR2A PPPlCA PRKACB
  • PCNTl CDC2 PRKACG PPPlCA PPP2CA PRKCE PRKAGl ARHA aktPathway Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT.
  • PIK3CA PIK3R1 BAD NFKBl YWHAH PPP2CA FOXO3ATNFSF6 alkPathway Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development.
  • ADP-ribosylation factors members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's.
  • AREs antioxidant response elements
  • Cyclin-dependent kinase inhibitor 2 A is a tumor suppressor that induces Gl arrest and can activate the p53 pathway, leading to G2/M arrest.
  • PRODH asbcellPathway B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response.
  • CALM2 MAP2K1 SHC1 RAFl CALM3 MEF2B GNAQ MAP2K4AGT MAP3K1 MEF2C
  • the tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair.
  • ATM ABLl NFKBIA NBSl MREl IARELA JUN
  • VAVl SOSl PRKCBl MAPK 14 PPP3 CC RACl JUN MAPK3 CALMl NFATC3 PLCGl SYTl CALM2 MAP2K1 NFATC2 SHCl BLNK PPP3CA CD79B
  • GPCRs G-protein coupled receptors
  • MAPK14MAPK3 F2 CALMl MYLK PLCGl BDK SYTl CALM2 MAP2K1 SHCl
  • FYN MAPK8 CDK5 blymphocytePathway B cells express the major histocompatibility complex (class II MHC). , immunoglobulins, adhesion proteins, and other factors on their cell surface.
  • HLA-DRA ICAMl CD80 TNFRSF5 CR2 ITGAL ITGB2
  • HLA-DRBl PTPRC CRl
  • FCGR2B botulinPathway BLACK SNAP25 CHRMl STXlA CHRNAl VAMP2 breast cancer estrogen signalling GEArray SPRRlB PAPPA NMEl
  • SFN FOS CDKNlA NCK2 EGR2 ACTB cacamPathway Calcium functions as a second messenger activating the calcium/calmodulin-dependent k inases, whic phosphorylate targets such as CREB.
  • CAMKlG calcineurinPathway Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes.
  • GPCR ligands such as angiotensin II that activate the EGF pathway.
  • MYC carml Pathway The methyltransferase CARM 1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4.
  • NROBl GRIPl HDAC5 TBP ERCC3 GTF2E1 HDAC6 NCOR2 NRIPl CREBBP caspase_activity BioCarta CASP4 CASPl CASP7 CASP3 CASP5 CASP6 CASPlO CASP14 caspasePathway Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets.
  • EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by CbI.
  • MAP2K1 GNBl ARHA ccr5Pathway CCR5 is a G-protein coupled receptor expressed in macrophages that recognizes chemokine ligands and is targeted by the HIV envelope protein GP 120.
  • the CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand.
  • TRAF6 DUSPl cdc25Pathway The protein phosphatase Cdc25 is phosphorylated by Chkl and activates Cdc2 to stimulate eukaryotic cells into M phase.
  • ATM CDC25C CDC2 WEEl CDC25A CDC25B YWHAH CHEKl MYTl cdc42racPathway PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation ofnew actin fibers.
  • ARPC2 ARPClB PIK3CA PIK3R1 PAKl ACTR2 ARHA j5 cdk5Pathway Cdk5, a regulatory kinase implicated in neuronal development, represses Mekl , which downregulates the MAP kinase pathway.
  • PCDHB4CX3CR1 PCDHB3 CDH17 IGSFl
  • PCDHB2 MADCAMl IL2 ITGA2 ITGA8
  • PCDHB 12 NRCAM PPFIAl E48 VCAMl DSC3 VWF CDH2 GP5 PCDHB6
  • ITGAM ITGA6 ITGAl 1 ICAP-IA FLRT3 ITGAlO TNC CDA08 ITGA3 ITGB5 BBS2
  • PTTGl CDKNU YWHAG cell cycle arrest Any process by which progression through the cell cycle is halted during one of the normal phases
  • ELF5 PTCH FSCNl ENPEP RBBP7 PRKCA IRF2 CDK7 STAT6 ARHGEFl BUBlB EPS8 MKI67 KRT16 PRKCM CDC14A BS69 EGFR LRPAPl TFDPl IGFBP4 CUL5 TPX2 ILIA FTHl LATSl CDK3 EPHB4 CSFl CSElL KIF2C SERPINFl PRL PDZKl PRG4 CDC2L2 PCNA IL3 FES TNFRSF9 AKRl C3 SFN CDK4 KNSL7 THPO UNQ429 CDK5 IL13 C8FW HDGF PRDXl GFIlB BLZFl
  • TNFSF8 IL15 PDGFA LMOl CDC25C
  • TNFSF9 NPY MAPREl LY86 MIA SKP2 UBE2V2 CXCLl TM4SF9 TNFSF7
  • CDKN2D CDK4 RBl CCNBl CCND3 CDKNlA CDKN2B ceramidePathway Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type.
  • RAFl MAP2K4TRAF2 TRADD MAP3K1 BCL2 FADD
  • MAPKl CASP8 NSMAF MAP2K1 MAPK8 cftrPathway The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface- localized beta-adrenergic receptor.
  • BAX TLNl BCL2L1 BID APAFl chrebpPathway Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels.
  • chREBP Carbohydrate responsive element binding protein
  • a heterodimer composed of Bmall and Clock acts as a transcription factor for proteins that regulate circadian rhythms, such as Per and Cry.
  • CDK5 classicPathway The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response.
  • Complement_Activation_Classical Processes involved in the classical complement cascade, which promotes microbial lysis, disposal of immune complexes, and regulation of other immune processes.
  • C2 ClQB ClQG Complement_Activation_Classical Processes involved in the classical complement cascade, which promotes microbial lysis, disposal of immune complexes, and regulation of other immune processes.
  • CIS C4A C6 compPathway Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis.
  • CDH 15 SELPLG ITGA3 TNS TIMP2 CDH6 ROCKl NCAM2 ARHGAPl ITGB5
  • CDH 18 CDH12 ITGAX CD44 MMP 13 CDH5 F2R RACl CD58 CDHI l ITGB4
  • CD68 CD24 TFE3 FCGR2B IFNG CD2 ILlB IFNBl HCAl 27 CD48 CD37
  • CD58 NKTR CD63 ILl 5 CD14 IFNAR2 CDlD IFNGRl BAGE CD47 CD59
  • MAPK12IL12RB1 RAN CRKL CAMK4
  • MAPK9 JAKl STATl TIAMl PTCH2 GRB7 TRAFl PTK2B
  • GRF2 PIK3CG WNT4
  • ROSl WNTl ITGBl GRB 14
  • SMO WNT2 TRAF6
  • MAPK13JAG1 IFNBl
  • AXINl ROCKl CMKORl
  • MAP3K5 AXIN2
  • MAPK10ITGB5 RELB JAG2 ITGAX SOSl CXCL3 IL15 MAP4K4IQGAP2
  • MAPK14RAC1 PRKAR2B MAPK3 PRKARlA AKTl ADCYl PRKACG
  • CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis.
  • HLA-DRBl CREBBP ctla4Pathway T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APCs CD80 or 86.
  • APC antigen-presenting cell
  • CD3Z PTPNI l ICOS CTLA4 GRB2 TRA@ LCK ICOSL CD86 PIK3CA CD3G
  • HLA-A ICAMl TNFRSF6 CD3D ITGB2 ITGAL TNFSF6 B2M cxcr4Pathway CXCR4 is a G-protein coupled receptor that responds to the ligand SDF-I by activating Ras and PI3 kinase to promote lymphocyte chemotaxis.
  • cytokinePathway Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen- dependent B and T cell response.
  • TNFRSF5 IFNAl ILlO deathPathway Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade.
  • CDSl CDC20 XRCC4 TERT MSH6 REV3L ERCCl H2AFZ XRCC5 PCNA MREI lA
  • MAP2K1 SHC1 ARHGAP5 PFNl FYN ARHA edgl Pathway The lipid SlP is an EDGl ligand promoting chemotaxis via Racl and cell survival and proliferation via ERK activation.
  • SMPD2 ITGB3 GNGTl PRKCBl PDGFRA SMPDl RACl MAPK3 AKTl PDGFA
  • EGF epidermal growth factor
  • EIF2 Eukaryotic initiation factor 2
  • EIF4A2 IRSl PTEN RPS6KB1 electronjransport BioCarta CYP4A11 CYPI lAl CYP39A1 CYP7A1 PTGIS CYBRDl
  • NDUFS6 COX7C COX6 A I NDUF V ITBDN 100 UCPl NDUFBl DAP13 NDUFA3COX7A2
  • Eph kinases are receptor tyrosine kinases that bind surface-expressed ephrin ligands and are active in neuronal development and platelet aggregation.
  • ITGBl SELP EPHA4 LlCAM RAPlB LYN ITGAl ACTAl FYN EPHBl eponfkbPathway
  • the cytokine erythropoietin (Epo) prevents stress-induced neuronal apoptosis by stimulating anti- apoptotic pathways through JAK2 kinase and NF-kB.
  • MAPK8 erbb3Pathway Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation.
  • UBE2D1 EGFR ERBB3 EGF NRGl erbb4Pathway ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors.
  • IL6 TGFBl CCL3 FLT3 etcPathway Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water.
  • the Ets transcription factors are activated by Ras and promote macrophage differentiation.
  • the extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade.
  • Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release.
  • VAVl SOSl PRKCBl PPP3CC MAPK3 JUN CALMl NFATC3 PIK3R1 PLCGl SYTl CALM2 MAP2K1 NFATC2 SHC1 MAP2K7PPP3CA RAFl
  • Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes.
  • the fMLP receptor is a G-protein coupled receptor in neutrophiles that recognizes formylated bacterial peptides and activates NADPH oxidase.
  • GABARAP GABRA6UBQLN 1 gata3 Pathway BioCarta ILl 3 GATA3 NFATCl PRKAR2A PRKACE ! JUNB IL5
  • CALMl GSK3A CALM2 AGL CALM3 PPP2R5C GSK3B UGP2 PPP2R3A
  • HTRlE GPRlO SREB3 CCRL2 CMKOR 1 HRH3 GPR27 CX3CR1 AD0RA2A
  • MAP2K2NFKB1 RBl CREBl
  • MAPKl MAP2K1 hdacPathway BioCarta IGFlR CABINl
  • MAPK14PPP3CC MAP2K6AKT1 MEF2D CALMl INS
  • MAPK8 BID CASP9 LLMMNNBB22 NFKBIA TNFRSFlA AARRHHGGDDIIBB GGSSNN TNFRSFlB
  • HLA-DRBl TNF HLA-DRA ILl 2B CSF3 IFNG IL5 IL8 IL12A
  • PCK2 PRKCZ IRSl RPS6KB1 SERPINB6 ARAFl GSK3B AKT2 PDPKl
  • ADRB3 DUSP14 SERPINEl SHC3 SREBFl SORBSl VEGF RRAS RPS6KA1
  • ETS2 MAP2K7PRKCQ ETSl RAFl MAPKl 3 TNF MAP2K4TRAF2 MAP3K1 BCL2
  • MAP kinase kinase activity GenMAPP MAPK10MAP2K3MAPK14MAP2K1 MAP2K6MAP2K'
  • ADHlC G6PC PGAM2 MAP00020_Citrate_cycle_TCA_cycle GenMAPP ACO2 MDHl MDH2 CS AACCOOll IDH2
  • CYP2D6 CYP4B1 ACADL ADHlA HADHB CDK3 GCDH CYP3A4 EHHADH ACATl CYP1A2 ADH5 CYPlAl ADH4 ACAA2 CYP4F8 ECHSl ADHlB ALDHlAl CYP2C8 ADHlC CYP2F1 CYP2A7 FACL3 CYP2A6 ACAAl CYP2C9 CYP3A7
  • HSD3B2 HSDI lBl CYP21A2 CYP17A1 HSDl 1B2 CYPI lBl AKRlDl
  • ARSE HSD3B2 STE ADH6 UGT2B15 SRD5A1 AKRlDl CYPI lBl HSD17B2
  • LDHC GOT2 LDHA MAP00280_ValineJeucine_and_isoleucine_degradation GenMAPP HADHB PCCA MCCCl ALDH3A2
  • AMDl G0T2 OAT ARG2 NNOOSS3 5 EEPPRRSS RARS GLUDl ALDHlBl VTIlB
  • CYP3A4 CYP19A1 ACP5 CYP1A2 ACPP CYPlAl CYP4F8 ACP2 CYP2J2 CYP3A5
  • AOC2 CYP2C8 MAOA CYP2A7 CYP2F1 CYP2A6 ABPl CYP2D6 CYP4B1 WARS2 ASMT
  • PIP5K2B INPPLl PIK3C2A INPP4A PLCDl IMPAl PIK3C2BPIK3CA PLCG2 PLCGl
  • FUTl FUT5 FUT3 MAP00602_Blood_group_glycolipid_biosynthesis_neolact_series GenMAPP FUT2 B4GALT3
  • MAP00740_Riboflavin_metabolism BLACK ACPI ACP5 ACP2 ACPP ACPT TYR MAP00760_Nicotinate_and_nicotinarnide_metabolism BLACK NT5C1B NP NMNATl NNMT
  • AMPH EPS 15 CALMl NME2 SYNJ2 SYTl CALM2 SYNJl PICALM PPP3CA BINl neurotransmittersPathway BLACK PNMT DBH TPHl HDC GADl TH neutrophilPathway BioCarta SELL ICAMl CD44 ITGAL ITGB2 ITGAM PECAMl SELE nfatPathway BioCarta MAPK14CALM1 PRKACC NFATC3 PIK3R1 EDNl SYTl NFATC2
  • NFKBl TNFAIP2 I RIPKl MYD88 TRAF6 ILlRl ngfPathway BioCarta RAFl NGFB SOSl KLK2 HRAS GRB2 JUN MAPK3 PIK3CA
  • PRKARlB SYTl CALM2 GRINl NOSl PPP3CA notchPathway BLACK NOTCHl PSENl FURIN DLLl RBPSUH ADAM17 nthiPathway BioCarta EP300 TNF CHUK NFKBIA MADH4 ILlB MAP3K7IL8 NR3C1
  • MAP3K9TGFB3 STATl MAP3K5 MAPKAPK2 DDIT3 RPS6KA5 CREBl MEF2A
  • HDACl PPARBP DVLl LDBl CTNNBl
  • APC CREBBP pkcPathway BioCarta GNAQ NFKBI ⁇ NFKBl PRKCA PRKCBl
  • ADRAIBPLCDI plcePathway BioCarta ADRB2 PTGERl ADCYl PRKACG PRKAR2A PRKARlB
  • PIK3CA NGFR AKT3 PIK3CD MAP2K2MAP2K1 SHCl CDKNlA ELKl ARHA salmonellaPathway BioCarta ARPC2 ACTR3 WASL ARPClB ARPC4 CDC42 ARPC3 WASFl RACl
  • MAP3K4MYEF2 MAPK10MAP3K12 ILlRl MAP2K5MAPK8
  • TNFRSF 13C TNFRSF 13B
  • TNFRSF17 NFKBl
  • TRAF6 MAPK8 TNFSFI: 5 tcapoptosisPathwayBioCarta CD3E TRB@ CD3Z CD3G TNFRSF6 CCR5 TRA@ CD3D
  • MAP2K4NFATC1 RASAl MAP3K1 HRAS GRB2 PRKCA TRA@ PIK3CA NF ATC4 NFKBl
  • TGFBR2 MADH2 CDHl MAP3K7IP1 MAP2K1 TGFBRl APC SKIL TGFBl CREBBP thlth2Pathway BioCarta IL2 IL12B HLA-DRA IFNG IL12RB1 IL12RB2 IL12A IL4
  • MAP3K1 SPTANl FADD LMNBl MADD DFFB RBl PAK2 CASP2 DFFA MAPK8 tnfr2Pathway BioCarta IKBKAP TRAF2 TANK MAP3K1 IKBKG CHUK NFKBIA MAP3K14

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Abstract

Disclosed are and methods for identifying treatments for diseases. Also disclosed are compositions for Acute Myeloid Leukemia.

Description

USE OF GENE SIGNATURES TO DESIGN NOVEL CANCER TREATMENT
REGIMENS
1. This application claims the benefit of U.S. Provisional Application No. 60/798,974, filed on May 9, 2006, which is incorporated by reference herein in its entirety. This application was made with government support under federal grants 5T32 CA09363 and National Cancer Institute (R01CA90446) as well as US Dept of Defense (DAMD 17-03- 1-0263). The Government has certain rights to this invention.
I. BACKGROUND
2. Current AML treatment involves the use of broadly toxic agents including anthracyclines (e.g. idarubicin and daunorubicin) and nucleoside analogs (e.g. cytarabine; Ara-C), which interfere with DNA replication and synthesis. By targeting cells primarily on the basis of active cell division, these regimens poorly discriminate between normal and malignant cells and cause substantial collateral damage to normal tissues, limiting their use due to toxicity especially in the elderly. Importantly, it was shown that AML-SCs are largely refractory to current chemotherapeutics (Guzman, MX. & Jordan, CT. (2004) Cancer Control 11, 97-104; Guzman, MX. et al. (2002) Proc Natl Acad Sci USA 99, 16220-5), thus representing a likely reservoir of malignant cells in disease relapse. Therefore, new treatments that target AML-SCs are needed as are methods of identifying said treatments.
II. SUMMARY
3. Disclosed are methods identifying novel treatments for diseases. Also disclosed are methods and compositions related to the treatment of Acute Myeloid Leukemia. IILBRIEF DESCRIPTION OF THE DRAWINGS
4. The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments and together with the description illustrate the disclosed compositions and methods.
5. Figure IA shows the flow cytometric profiles of a representative AML specimen treated with a sublethal concentration of PTL (2.5 μM), ciclopirox (20 μM), or the combination of both drugs (ciclo + PTL) for 24 hours. Post-treatment viability was determined for CD34+ cells using flow cytometry (annexin V and 7-AAD). 6. Figure IB shows the viability relative to untreated control for CD34+CD38- primitive cells treated with ciclopirox, PTL, or ciclopirox and PTL. Viability indicates % of cells that are Annexin V and 7- AAD negative. Error bars represent standard error of the mean. Black bars represent normal cells, white bars are AML (N=3). 7. Figure 1C shows the progenitor analyses using methylcellulose colony-formation assays. Normal erythroid, myeloid, and AML colony forming units are shown with PTL + ciclopirox relative to untreated controls. Error bars represent the standard error of the mean. Black bars are normal cells. (N=4). White bars are AML (N=5).
8. Figure 2A shows viability relative to untreated control for CD34+CD38- primitive cells treated 1 μM or 2 μM celastrol. Viability indicates % of cells that are
Annexin V and 7-AAD negative. Error bars represent standard error of the mean. Black bars represent normal cells, white bars are AML. N=4 per condition.
9. Figure 2B shows the results of methylcellulose colony assays of cells treated with 1 μM or 2 μM celastrol. Normal erythroid, myeloid, and AML colony forming units are shown relative to untreated controls. Error bars represent the standard error of the mean. Black bars are normal cells. White bars are AML. N = 3 per condition.
10. Figure 2C shows flow cytometric analyses of a representative AML specimen gated on CD34+CD38-CD123+ cells. Cells were treated with vehicle, 5 μM wortmannin, 2.5 μM PTL, or 5 μM wortmannin + 2.5 μM PTL. Annexin V (x-axis) is shown compared to 7-AAD (y-axis).
11. Fig. 2D shows the viability relative to untreated control for CD34+CD38- primitive cells treated with 2.5 μM PTL, 5 μM wortmannin, or the combination of both. Viability indicates % of cells that are Annexin V and 7-AAD negative. Error bars represent standard error of the mean. N=5 per condition. 12. Figure 2E shows the results of methylcellulose colony assays of cells treated with
2.5 μM PTL, 5 μM wortmannin, or 2.5 μM PTL + 5 μM wortmannin. Normal erythroid, myeloid, and AML colony forming units are shown relative to untreated controls. Error bars represent the standard error of the mean. Black bars are normal cells. White bars are AML. N =3 per condtion. 13. Figure 3 A shows flow cytometric profiles of CD34+CD38- cells untreated treated with 5 μM troglitazone, 20 μM prochlorperazine, or the combination of both for 24 hours. Annexin V (x-axis) is shown compared to 7-AAD (y-axis). 14. Fig. 3B shows viability relative to untreated control for CD34+CD38- primitive cells treated with 5 μM troglitazone, 20 μM prochlorperazine, or the combination of both for 24 hours. Viability indicates % of cells that are Annexin V and 7- AAD negative. Error bars represent standard error of the mean. Black bars represent normal cells, white bars are AML. N=3 per condition.
15. Fig. 3C shows the results of Methylcellulose colony assays of cells treated with 5 μM troglitazone, 20 μM prochlorperazine or both. Normal erythroid, myeloid, and AML colony forming units are shown relative to untreated controls. Error bars represent the standard error of the mean. Black bars are normal cells. White bars are AML. N=3 per condition.
16. Figure 4 shows the viability determined by flow cytometry relative to untreated control for CD34+ cells treated with ciclopirox, PTL, or ciclopirox and PTL. Viability indicates % of cells that are Annexin V and 7- AAD negative. Error bars represent standard error of the mean. Black bars represent normal cells, white bars are AML. N=3 per condition.
17. Figure 5 shows the viability relative to untreated control for CD34+ cells treated with 5 μM troglitazone, 20 μM prochlorperazine, or the combination of both. Viability indicates % of cells that are Annexin V and 7- AAD negative. Error bars represent standard error of the mean. Black bars represent normal cells, white bars are AML N=3 per condition.
IV. DETAILED DESCRIPTION
18. Before the present compounds, compositions, articles, devices, and/or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods or specific recombinant biotechnology methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. A. Definitions
19. As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a pharmaceutical carrier" includes mixtures of two or more such carriers, and the like. 20. Ranges can be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "10" is disclosed the "less than or equal to 10"as well as "greater than or equal to 10" is also disclosed. It is also understood that the throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point "10" and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.
21. m this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:
22. "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.
23. "Primers" are a subset of probes which are capable of supporting some type of enzymatic manipulation and which can hybridize with a target nucleic acid such that the enzymatic manipulation can occur. A primer can be made from any combination of nucleotides or nucleotide derivatives or analogs available in the art which do not interfere with the enzymatic manipulation. 24. "Probes" are molecules capable of interacting with a target nucleic acid, typically in a sequence specific manner, for example through hybridization. The hybridization of nucleic acids is well understood in the art and discussed herein. Typically a probe can be made from any combination of nucleotides or nucleotide derivatives or analogs available in the art.
25. A "decrease" can refer to any change that results in a smaller amount of AML cell activity. Thus, a "decrease" can refer to a reduction in an activity. Thus, for example, a decrease can refer to a change in the symptoms of a disorder such that the symptoms are less than previously observed. A decrease can also refer to a change in the rate or progression of a disease or condition. Thus, for example, a complete inhibition or slowed rate of growth or metastisis of a tumor would be a decrease. It is understood that a decrease in the amount in AML cell activity can include but is not limited to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% decrease. A substance is also understood to decrease the genetic output of a gene when the genetic output of the gene product with the substance is less relative to the output of the gene product without the substance. Also for example, a decrease can be a change in the symptoms of a disorder such that the symptoms are less than previously observed.
26. An "increase" can refer to any change that results in a larger amount of an AML cell activity. Thus, for example, an increase in the amount of an AML cell activity can include but is not limited to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% increase.
27. "Inhibit," "inhibiting," and "inhibition" mean to decrease an activity, response, condition, disease, or other biological parameter. This can include but is not limited to the complete ablation of the activity, response, condition, or disease. This may also include, for example, a 10% reduction in the AML cell activity, response, condition, or disease (such as AML) as compared to the native or control level. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels.
28. Herein, "perturbations" refers to any manipulation to a cell that results in a change in the molecular abundances of the genes and proteins of the cell. Thus, for example, a perturbation can be but is not limited to pharmaceutical agents, chemical agents, environmental conditions such as stress, gamma irradiaition, UV-irradiation, mutagens, and gene therapy (including but not limted to vectors designed to overexpress a gene, introduce a exogenous gene, or reduce the expression of an overexpressed gene). Typically, perturbations refer pharmaceutical agents or manipulations used in the course of treatment for a disease. 29. "Treatment," "treat," or "treating" mean a method of reducing the effects of a disease or condition. Treatment can also refer to a method of reducing the disease or condition itself rather than just the symptoms. The treatment can be any reduction from native levels and can be but is not limited to the complete ablation of the disease, condition, or the symptoms of the disease or condition. Therefore, in the disclosed methods, treatment" can refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of an established disease or the disease progression or in an assay for a disease progression, such as the acute myeloid leukemia (AML) assays described herein. For example, a disclosed method for reducing the effects of AML is considered to be a treatment if there is a 10% reduction in one or more symptoms of the disease in a subject with the disease when compared to native levels in the same subject or control subjects. Thus, the reduction can be a 10, 20, 30, 40, 50, 60, 70, 80, 90, 100%, or any amount of reduction in between as compared to native or control levels. It is understood and herein contemplated that "treatment" does not necessarily refer to a cure of the disease or condition, but an improvement in the outlook of a disease or condition. 30. "Obtaining a tissue sample" or "obtain a tissue sample" means to collect a sample of tissue from a subject or measure a tissue in a subject. It is understood and herein contemplated that tissue samples can be obtained by any means known in the art including invasive and non-invasive techniques. It is also understood that methods of measurement can be direct or indirect. Examples of methods of obtaining or measuring a tissue sample can include but are not limited to tissue biopsy, tissue lavage, aspiration, tissue swab, spinal tap, magnetic resonance imaging (MRI), Computed Tomography (CT) scan, Positron Emission Tomography (PET) scan, and X-ray (with and without contrast media). 31. Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon.
B. Methods of screening for compositions having anti-cancer activity
32. Disclosed herein are methods for identifying a treatment comprising one or more perturbations having anti-cancer activity comprising a) obtaining one or more first cells, b) obtaining one or more second cells, wherein the second cell has been subject to a modification to differ from the first cell, c) performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d) performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e) performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f) identifying perturbations that modulate the molecular abundance of one or more molecule sets, g) selecting combinations of perturbations wherein each perturbation modulates at least one molecule set arising from the comparison of the first and second cells, and h) testing whether the combination of perturbations recapitulates the desired biological outcome arising from the comparison of the first and second cells.
33. Throughout these methods it is understood that it may be advantageous to preselect molecules and molecule sets prior to analysis. The identification of such molecules or molecule sets can be determined through research or the literature. Thus disclosed herein are methods, wherein prior to analysis a preselection of molecules or molecule sets has been made.
34. It is contemplated herein that first cell and second cell similar with the exception of the modification to the second cell. It is understood herein that "modification" can refer to any manipulation of a cell that results in a change in molecular abundances of the second cell relative to the first cell. Thus modification can include but is not limited to contacting a cell with an agent wherein the agent results in a change in the molecular abundance of the cell relative to the first cell, subjecting the cell to a mutagen (including but not limited to chemical mutagens, UV light, irradiation), and genetic manipulations such as the overexpression or repression of one or more genes by any known method including the use of genes or proteins that block transcription, translation, and compete for resources available to a cell. Thus, modification in one aspect can mean subjecting the second cell to a treatment, for example, a treatment for cancer. Thus, for example, disclosed herein are methods wherein the treatment preferentially affects a cancer stem cell and not an non- cancer cell. Also disclosed herein are methods for identifying a treatment comprising one or more perturbations having anti-cancer activity comprising a) obtaining one or more first cells, b) obtaining one or more second cells, wherein the second cell is a mutated cell, and wherein the mutated cell arises from a cell similar to the first cell, c) performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d) performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e) performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f) identifying perturbations that modulate the molecular abundance of one or more molecule sets, g) selecting combinations of perturbations wherein each perturbation modulates at least one molecule set arising from the comparison of the first and second cells, and h) testing whether the combination of perturbations recapitulates the desired biological outcome arising from the comparison of the first and second cells. 35. It is understood and herein contemplated that the first and second cell can comprise any cell from which a comparison can be made. Thus, for example, the first and/or second cell can comprise a cell or cells derived from a cell line. It is disclosed herein that the cell line can be a cancer cell line. Alternatively, the first and/or second cell can comprise a cell obtained from a subject such as a primary cell. It is further understood that the first and/or second cell can be a "normal" cell derived or obtained from any mammalian tissue or can be a cell with a naturally occurring mutation or cancerous cell. Thus, for example, the first and/or second cell can be a cancerous cell. It is further contemplated herein that a cancerous first or second cell could be derived from any cancer type. For example, disclosed herein are methods wherein the first and/or second cell is derived from a cancer selected from the group consisting of lymphoma, B cell lymphoma, T cell lymphoma, mycosis fungoides, Hodgkin's Disease, leukemias, myeloid leukemia, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of head and neck, lung cancers such as small cell lung cancer and non-small cell lung cancer, neuroblastoma/glioblastoma, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, liver cancer, melanoma, squamous cell carcinomas of the mouth, throat, larynx, and lung, gastric cancer, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial cancer, bone cancers, renal cancer, bladder cancer, genitourinary cancer, esophageal carcinoma, large bowel cancer, metastatic cancers hematopoietic cancers, sarcomas, Ewing's sarcoma, synovial cancer, soft tissue cancers; and testicular cancer. It is further contemplated herein that the first and/or second cell can be a cancer stem cell. 1. Cancer Stem Cells
36. Stem cells have three distinctive properties: self-renewal (i.e., at cell division, one or both daughter cells retain the same biologic properties as the parent cell), the capability to develop into multiple lineages, and the potential to proliferate extensively. The combination of these three properties makes stem cells unique. The attribute of self-renewal is especially notable, because its subversion is highly relevant to oncogenesis and malignancy. Aberrantly increased self-renewal, in combination with the intrinsic growth potential of stem cells, may account for much of what is considered a malignant phenotype.
37. Biologically distinct and relatively rare populations of "tumor-initiating" cells have been identified in cancers of the hematopoietic system, brain, and breast. These cells have the capacity for self-renewal, the potential to develop into any cell in the overall tumor population, and the proliferative ability to drive continued expansion of the population of malignant cells. Accordingly, the properties of tumor-initiating cells closely parallel the three features that define normal stem cells. Malignant cells with these functional properties have been termed "cancer stem cells"
38. The key issue for consideration with regard to tumor biology is that a small subgroup of the cells in a tumor — the cancer stem cells — are essential for its growth. The concept of cancer stem cells can, however, vary in different contexts. For example, cancer stem cells can be the source of all the malignant cells in a primary tumor, they can compose the small reservoir of drug-resistant cells that are responsible for relapse after a chemotherapy induced remission, or they can give rise to distant metastases. The biologic features of cancer stem cells in each of these instances may differ, suggesting that the acquisition of features associated with tumor progression, such as genetic instability and drug resistance, will also be associated with cancer stem cells. 39. Cancer stem cells are readily evident in chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML), and they have been implicated in acute lymphoblastic leukemia (ALL). CML stem cells have a well-described stem-cell phenotype and a quiescent cell-cycle status. Similarly, AML stem cells are mostly quiescent, suggesting that conventional antiproliferative cytotoxic regimens are unlikely to be effective against them. AML stem cells have surface markers, such as the interleukin-3-receptor a chain, that are not present on normal stem cells. These markers are useful for antibody- based or other related therapeutic regimens. Specifically contemplated herein are methods of identifying a composition having anti-cancer activity wherein the first and/or second cells are leukemia stem cells. Also contemplated herein are methods of identifying a composition having anti-cancer activity comprising AML or CML stem cells.
40. The disclosed compositions as well as compositions identified through the disclosed methods can be used to treat any disease where uncontrolled cellular proliferation occurs such as cancers, as well as any of the methods described herein can be used for any uncontrolled cellular proliferation disesease, such as cancer can also be used. It is also understood and herein contemplated that the disclosed methods of identifying a compostion having anti-cancer activity comprises treating a cell, wherein the treated cell is a cancer stem cell wherein the treatment preferentially affects the cancer stem cell, not a non-cancer cell A non-limiting list of different types of cancers that can be treated by the methods and compositions disclosed herein or that can be the source of primary and treated cells used in the methods disclosed herein is as follows: lymphomas (Hodgkins and non- Hodgkins(including but not limited to: diffuse large cell, Burkitt's, mantle cell, follicular, and T cell)), leukemias, including but not limited to Acute myelogenous leukemia, Acute lymphoblastic leukemia, Chronic myelogenous leukemia (chronic, accelerated, and blast crisis), Chronic lymphocytic leukemia, Myelodysplastic syndromes, Myeloproliferative diseases/syndromes, Multiple myeloma, carcinomas, carcinomas of solid tissues, squamous cell carcinomas, adenocarcinomas, sarcomas, gliomas, high grade gliomas, blastomas, neuroblastomas, plasmacytomas, histiocytomas, melanomas, adenomas, hypoxic tumours, myelomas, AIDS-related lymphomas or sarcomas, metastatic cancers, all forms of hematologic cancer, or cancers in general.
41. A representative but non-limiting list of cancers that the disclosed compositions can be used to treat as well as any of the methods described herein can be used for any uncontrolled cellular proliferation disease, such as cancer can also be used is the following: lymphoma, B cell lymphoma, T cell lymphoma, mycosis fungoides, Hodgkin's Disease, non-hodgkin's lymphomas, myeloid leukemia (acute and chronic), lymphoid leukemia (acute and chronic), multiple myeloma, neuroblastoma, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of head and neck, lung cancers such as small cell lung cancer and non-small cell lung cancer, neuroblastoma/glioblastoma, ovarian cancer, skin cancer, liver cancer, melanoma, squamous cell carcinomas of the mouth, throat, larynx, and lung, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial cancer, renal cancer, genitourinary cancer, pulmonary cancer, esophageal carcinoma, head and neck carcinoma, large bowel cancer, hematopoietic cancers; testicular cancer; colon and rectal cancers, prostatic cancer, or pancreatic cancer. It is also understood that the disclosed treatments can be used to treat any known cancer. Thus, for example, it is understood that the disclosed treatments can be used to treat acute myeloid leukemia.
42. Compounds disclosed herein may also be used for the treatment and as well as any of the methods described herein can be used for any uncontrolled cellular proliferation disease, such as cancer can also be used of precancer conditions such as cervical and anal dysplasias, other dysplasias, severe dysplasias, hyperplasias, atypical hyperplasias, myelodysplastic syndromes, myeloproliferative diseases, and neoplasias. Thus, disclosed herein are methods for identifying perturbations having anti-cancer activity and treatments for cancer wherein the cancer is a blood malignancy such as AML or CML. 2. Acute myeloid leukemia (AML) 43. Acute myelogenous leukemia (AML) is a malignant disease characterized by an aberrant accumulation of immature myeloid hematopoietic cells. Although remission can be achieved in most patients, relapse is common and long-term survival is poor for most cases. Studies using a variety of experimental systems have shown that AML arises from a rare population of leukemic stem cells (LSCs). LSCs share some antigenic features with normal hematopoietic stem cells (HSCs), such as CD34+, CD38-, CD71-, and HLA-DR-, but can be phenotypically distinguished from HSCs by virtue of several disparate markers. In addition, LSCs, like HSCs, are largely quiescent and display heterogeneity within the stem cell compartment. As a consequence of these common features, it has been relatively difficult to define strategies to differentially target the LSC population. However, recent studies have demonstrated that LSCs do display certain unique molecular properties such as constitutive activation of nuclear factor KB (NF-KB), expression of CD 123, and potentially elevated levels of interferon regulatory factor 1 (IRF-I) and death-associated protein (DAP) kinase. Features such as these suggest that LSC-specific targeted therapy should be feasible using a variety of strategies.
44. Current chemotherapy regimens for AML commonly use drugs such as nucleoside analogs (eg, cytosine arabinoside [Ara-C]) and anthracyclines (eg, idarubicin, daunorubicin) that interfere with DNA replication and induce apoptosis primarily in replicating cells. Since LSCs are mostly quiescent, it is likely that at least some malignant stem cells are refractory to standard chemotherapy and may thereby contribute to relapse. Moreover, current regimens may not effectively discriminate between normal and malignant cells. Consequently, substantial damage to normal tissues is likely to occur in the course of standard treatments. For this reason, it is important to identify therapies that can specifically target the LSC population without affecting normal cells.
3. Methods of meausuring molecular abundance
45. The disclosed methods of identifying a composition having anti-cancer activity utilize molecular abundance techniques. It is herein contemplated that molecular abundance techniques can include but are not limited to gene expression arrays and protein expression arrays. For example, a genome tiling array which can be used in conjunction with for example --ChIP on chip — to capture epigenetic differences associated with a biological state (such as drug treated vs. untreated). Also, it is herein contemplated that other methods can be used, for example, differential histone acetylation or differential DNA methylation. Moreover, the differential genetic analysis technique can include gene set analysis. Such analysis allows for the identification of drug combinations determined by looking for epigenetic changes. It is therefore understood and herein contemplated that the disclosed molecular abundance techniques include but are not limited to Northern analysis, RNAse protection assay, PCR, QPCR, RT-PCR, RT-PCR arrays, microRNA arrays, exon arrays, genome microarray, low density PCR array, oligo array, SAGE, high throughput sequencing, protein microarray, antibody-based or protein activity-based assays and mass spectrometry. Thus, for example, disclosed herein are methods of identifying a composition having anti-cancer activity wherein differential genetic analysis technique is gene expression. Also disclosed are methods wherein the gene expression analysis is performed using a microarray.
46. The disclosed methods utilize "molecule sets" to categorize genes and/or proteins based on a given relationship. Thus, it is understood and herein contemplated that molecule sets can refer to protein sets or gene sets. It is understood and herein contemplated that a molecule set can consist of any number of molecules greater than or equal to two. The specific molecules in a molecule set can share a known biological relationship such as "heat shock proteins" as defined by wet bench work or by searching the literature. Alternatively, the specific molecules in the molecule set can share a computationally defined relationship, for example, genes predicted by a computational algorithm to commonly possess NfkB binding sites in their promoter regions. Also, a molecule set can consist of a group of molecules shown to have a mathematical relationship by for example hierarchical clustering or k-means clustering. It is further understood that a molecule set can consist of a group of molecules arising from microarray analysis, for example, the top N genes upregulated or downregulated by "things": e.g. a drug or siRNA knockdown or a xenobiotic. Thus, from the Connectivity Map, it can be said there are 453 gene sets consisting of the top 100 genes upregulated in each instance and an additional 453 gene sets consisting of the top 100 genes downregulated in each instance. Thus, for example, gene sets can include but are not limited to the following:
41bbPathway TNF-type receptor 4- IBB is bound by TRAFl to activate the MAP kinase pathway in activated T cells. IL2 TRAF2 MAP3K1 IFNG CHUK NFKBIA MAPK 14 IL4 RELA JUN ATF2
MAP4K5TNFRSF9 TNFSF9 MAP3K5 IKBKB NFKBl MAPK8 ace2Pathway Angiotensin-converting enzyme 2 (ACE2) digests the blood-pressure regulator angiotensin II (AGT) ultimately to the vasodilator AGTl -7. COL4A3 COL4A1 COL4A5 AGT COL4A6 AGTRl COL4A2 REN
COL4A4 ACE2 CMAl AGTR2 acetaminophenPathway Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP3A PTGS2 CYP 1A2 PTGSl NRl 13
CYP2E1 achPathway Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway. RAPSN TERT MUSK PTK2 CHRNG
AKTl PIK3CA PIK3R1 BAD PTK2B YWHAH SRC CHRNBl FOXO3ATNFSF6 actinYPathway The Arp 2/3 complex localizes to the Y-junction of polymerizing actin fibers that enable lamellipod extension and consequent cell motility. ACTR3 ABI-2 WASL ARPC4 NTRKl ARPC3 WASFl RACl WASF2 ACTAl ARPClAPIR ARPC2 ARPClB NCKAPl NCKl WASF3 ACTR2 PSMA7 agpcrPathway G-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis. PRKAR2A GNGTl
PRKACB PRKCBl PRKCA PRKAR2B PRKARlA PRKACG PRKARlB
GPRK2L ARRBl GNAS GNBl ahspPathway Alpha-hemoglobin stabilizing protein (AHSP) prevents precitipation of hemoglobin alpha-subunits.
CPO HMBS ALASl ERAF HBA2 ALAD HBAl GATAl ALAS2 UROS UROD
HBB FECH aifPathway BLACK ADPRT PDCD8 BCL2L1 CYCS akapl3Pathway A-kinase anchor protein 13 (AKAP 13) localizes protein kinase A holoenzyme and is a nucleotide exchange factor for Rho/Rac. EDG4 PRKACG PRKAR2A PRKACB PRKAGl GNA12
PRKAR2B EDG2 AKAP 13 ARHA EDG7 akap96Pathway BioCarta CDC2 DDX5 PRKACG PRKAR2A PPPlCA PRKACB
CNAPl CCNBl PPP2CA PRKAGl AKAP8 PRKAR2B akapCentrosomePathway Anchoring protein AKAP350 keeps protein kinase A bound to the centrosome during interphase. PRKAR2A AKAP9 PRKACB PRKAR2B PCNT2 PRKCLl MAP2
PCNTl CDC2 PRKACG PPPlCA PPP2CA PRKCE PRKAGl ARHA aktPathway Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT.
FOXO1ACASP9 PDPKl GHR CHUK NFKBIA GHl HSPCA RELA AKTl MLLT7
PIK3CA PIK3R1 BAD NFKBl YWHAH PPP2CA FOXO3ATNFSF6 alkPathway Activin receptor-like kinase 3 (ALK3) is required during gestation for cardiac muscle development. TGFB2 MADH4 MAP3K7CHRD WNTl RFCl NKX2-5 BMP2 ATF2 MYL2 MADH6
NPPB BMP5 TGFBR3 MADHl CTNNBl APC TGFBRl NPPA BMPlO NOG GSK3B
MEF2C BMPR2 TCFl AXINl TGFB3 ACVRl TGFBR2 GATA4 FZDl DVLl MADH5
BMPRlA BMP4 TGFBl BMP7 altemativePathway The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. C5 C7 C8A C3 DF BF C6
C9 PFC amiPathway Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. TRB@ CD3E PRKAR2A HLA-DRA CD3Z ZAP70 GNGTl PRKACB TRA@ LCK PRKAR2B CD4 PRKARlA
PTPRC CSK PRKACG ADCYl CD3G PRKARlB GNAS GNBl CD3D
HLA-DRBl CREBBP anthraxPathway BLACK MAP2K2MAP2K1 appPathway BLACK PSENl ADAMlO APP BACE arapPathway ADP-ribosylation factors (ARFs), members of the Ras superfamily, regulate eukaryotic vesicular trafficking and activate phospholipase D's. PSCD4 DDEFl GBFl KDELRl ARFGEF2 COPA
BIGl DDEF2 CENTD2PSCD3 COP KDELR3PSCD2 CLTB ARFl PSCDl ARFGAPl
GPLDl CLTA KDELR2ARFGAP3 CENTDl arenrQPathway Nrfl and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control. MAFG PRKCBl MAFK PRKCA MAPK14FXYD2 JUN
MAFF KEAPl CREBl MAPKl FOS NFE2L2 MAPK8 arfPathway Cyclin-dependent kinase inhibitor 2 A is a tumor suppressor that induces Gl arrest and can activate the p53 pathway, leading to G2/M arrest. ABLl E2F1 POLRlD TWISTl RACl POLRlC MDM2 TBX2
PIK3CA TP53 PIK3R1 POLRlB CDKN2A RBl POLRlA MYC argininecPathway Related catabolic pathways process arginine, histidine, glutamine, and proline through glutamate to alpha-ketoglutamate, which feeds into the citric acid cycle. GLS OAT ALDH4A1 GLUDl ARGl
PRODH asbcellPathway B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. IL2 HLA-DRA TNFSF5 TNFRSF6 CD80 TNFRSF5 IL4 CD4 TNFSF6 HLA-DRBl ILlO CD28 atlrPathway Binding of angiotensin II to ATl-R activates Ca2+ signaling and the JNK pathway. EGFR
SOSl PRKCBl RACl MAPK3 JUN ATF2 MEF2D CALMl AGTRl PAKl SYTl
CALM2 MAP2K1 SHC1 RAFl CALM3 MEF2B GNAQ MAP2K4AGT MAP3K1 MEF2C
PTK2 HRAS PRKCA GRB2 PTK2B MAP2K2MEF2A MAPKl SRC ELKl MAPK8 atmPathway The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ATM ABLl NFKBIA NBSl MREl IARELA JUN
RAD50 TP73 RBBP8 MDM2 GADD45A TP53 NFKBl CHEK2 RAD51 CDKNlA
CHEKl MAPK8 BRCAl atrbrcaPathway BRCAl and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM HUSl FANCE FANCA NBSl TREXl
MREI lAATR RAD50 BRCA2 RAD17 FANCD2TP53 RADl FANCC CHEK2 FANCF
RAD9A RAD51 CHEKl BRCAl FANCG badPathway When phosphorylated, BAD is inhibited by sequestration; when non-phosphorylated, it promotes apoptosis by inactivating pro-survival BCL-XL and BCL-2. CSF2RB IGFlR PRKAR2A KITLG PRKACB KIT BCL2 PRKAR2B IL3 AKTl PRKARlA IGFl
ADCYl PRKACG PIK3CA IL3RA PIK3R1 PRKARlB BAD BAX YWHAH
BCL2L1 bbcellPathway Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. HLA-DRA
TNFSF5 TNFRSF6 TNFRSF5 CD4 TNFSF6 HLA-DRBl CD28 bcl2family_and_reg_network GEArray BIK BCL6 AKT2 BCL2 BCL2A1 IL3 AKTl BAKl
APBA2BP GAPD IGFl BAD BCL2L2 BAX SFN NCBP2 CASP8 MCLl
BCL2L1 BAGl ARHA BID ACTB APAFl bcrPathway B cell antigen receptors (BCRs) activate tyrosine kinases and transiently increase tyrosine phosphorylation on binding to antigen. VAVl SOSl PRKCBl MAPK 14 PPP3 CC RACl JUN MAPK3 CALMl NFATC3 PLCGl SYTl CALM2 MAP2K1 NFATC2 SHCl BLNK PPP3CA CD79B
RAFl CALM3 PPP3CB NFATCl MAP3K1 HRAS PRKCA LYN GRB2 BTK CD79A
NFATC4 FOS SYK ELKl MAPK8 betaoxidationPathway BLACK ACADL ACATl ACADM ECHSl ACADS HADHA biopeptidesPathway Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. CAMK2D STAT5A GNGTl JAK2 SOSl PRKCBl
MAPK14MAPK3 F2 CALMl MYLK PLCGl BDK SYTl CALM2 MAP2K1 SHCl
STAT3 AGTR2 CALM3 RAFl GNAI l GNAIl AGT CAMK2G HRAS PRKCA
CAMK2A GRB2 STATl MAPT CAMK2B PTK2B MAP2K2MAPK1 GNBl
FYN MAPK8 CDK5 blymphocytePathway B cells express the major histocompatibility complex (class II MHC). , immunoglobulins, adhesion proteins, and other factors on their cell surface. HLA-DRA ICAMl CD80 TNFRSF5 CR2 ITGAL ITGB2 HLA-DRBl PTPRC CRl FCGR2B botulinPathway BLACK SNAP25 CHRMl STXlA CHRNAl VAMP2 breast cancer estrogen signalling GEArray SPRRlB PAPPA NMEl ATF2 F3 TOP2A CLDN7
CTSD CTNNB 1 MT3 MAP2K7ITGA6 TFF3 PTGS2 FHL5 MLP PLAU IL6R
CCNEl TP53 ID2 CCNE2 IGFBP2 GATA3 RAC2 CD44 GSN ITGB4 ERBB2
CCNAl CCNDl STC2 PPIA SLC7A5 SCGB 1D2 THBS2 CDKNlB C3
CCNA2 TGFA GABRP NFYB IL6 TNFSF6 KLK5 FOSLl DLCl KRTl 8 KRTl 9
CTSB IL6ST RPL27 FGFl FLRTl CYP19A 1 NGFR PPP1R15A SERPINEl
CLU IL2RA SCGB2A2 BCL2 HSPBl HMGBl SCGB2A1 MUCl TNFAIP2
VEGF TFFl MKI67 CDKN2A TNFRSF6 TIE AZGPl ESRl EGFR
ESR2 JUN RPL13A S100A2 KLF5 BPAGl SERPINA3 NGFB KRTHB6KIT
SERPINB5 PGR AR GAPD THBSl CDHl THBS4 BAD BCL2L2 GNAS
COL6A1 CDKNlA BAGl ACTB PTEN ca nf at signalling GE Array IL13 CD3Z EGR3 XPO5 RELA PTPRC GRLFl SLA CALMl
TRPV6 ITK NFATC2 MAP2K7PPP3R1 CALM3 MEF2B TNF EP300 NFATCl TRAF2
GSK3B IFNG ILlB HRAS CNRl PINl MEF2A ILlO CREBBP GATA3 VAVl
JUNB FCGR3ANFAT5 CD3G GSK3A PAKl SP3 CALM2 PPIA MYF5 FKBPlB
IL8 CAMK4 MAPK9 GATA4 TNFSF5 IL6 TNFSF6 FLJ14639 CD3E OPRDl
FOSLl ICOS MAPK14IL4 MEF2D NFKBIB NFATC3 IL8RA IL2RA BCL2 NUP214
IFNBl VEGF VAV3 CSNK2A1 KPNA5 P2RX7 IFNAl VAV2 TGFBl MAPK8
IL2 CABINl CSNK2B CTLA4 SPl PPP3CC RPLl 3 A CSF2 NPPB KPNB3 NFKB2
CEBPB PPP3CB FCERlA NFKBIE IL3 CD69 GAPD CAMK2B NFATC4 BAD
SFN FOS CDKNlA NCK2 EGR2 ACTB cacamPathway Calcium functions as a second messenger activating the calcium/calmodulin-dependent k inases, whic phosphorylate targets such as CREB. CALM3 CAMK2D CAMKKl CAMKl CAMK2G
CAMK2A CAMKK2 CAMK4 CAMK2B CALMl CREBl SYTl CALM2
CAMKlG calcineurinPathway Increased intracellular calcium activates the phosphatase calcineurin in differentiating keratinocytes.
CALM3 PPP3CB GNAQ NFATCl MARCKS PRKCBl SPl PRKCA PPP3CC CALMl
NF ATC3 PLCGl NFATC4 SP3 SYTl CALM2 NFATC2 CDKNlA PPP3CA cardiacegfPathway Cardiac hypertrophy, a response to high blood pressure, is stimulated by GPCR ligands such as angiotensin II that activate the EGF pathway. ADAM 12 EGFR AGT EGF PRKCBl HRAS
PRKCA RELA JUN EDNRA EDNRB EDNl PLCGl NFKBl FOS AGTR2 ARHA
MYC carml Pathway The methyltransferase CARM 1 interacts with transcription factors such as CBP/p300 and methylates histones H3 and H4. EP300 PRKAR2A RXRA PRKACB CARMl PRKAR2B
RARA NCOA3 PRKARlA PRKACG PRKARlB CREBl CREBBP carm-erPathway Methyltransferase CARMl methylates CBP and co-activates estrogen receptors via Gripl .
ESRl CARMl SHARP HDAC4 REA HDAC2 HIST2H3C CCNDl PELPl HDACl
PPARBP BRCAl HDAC3 EP300 SRAl MEF2C GTF2F1 P0LR2A PPARGCl GTF2A1
NROBl GRIPl HDAC5 TBP ERCC3 GTF2E1 HDAC6 NCOR2 NRIPl CREBBP caspase_activity BioCarta CASP4 CASPl CASP7 CASP3 CASP5 CASP6 CASPlO CASP14 caspasePathway Caspases are cysteine proteases active in apoptosis; caspase-8 and 9 cleave and activate other caspases, while 3, 6, and 7 cleave cellular targets.LMNA CASP9 LMNB2 CASP4 BIRC3 CASPl ARHGDIB
CASP6 LMNBl CYCS PRFl GZMB DFFB CASP7 CASP3 BIRC4 ADPRT BIRC2
CASP8 CASP2 CASPlO DFFA APAFl cblPathway Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by CbI. EGFR CBL EGF PRKCBl GRB2 PDGFRASH3KBP1
PRKCA SH3GLB2 MET SH3GLB1 SRC CSFlR ccr3Pathway CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. PIK3C2G RAFl NOXl GNAQ CCLI l GNGTl PTK2 PRKCA HRAS PRKCBl
PPP1R12B CCR3 CFLl MAPK3 R0CK2 PLCBl MYL2 LIMKl GNAS MAPKl
MAP2K1 GNBl ARHA ccr5Pathway CCR5 is a G-protein coupled receptor expressed in macrophages that recognizes chemokine ligands and is targeted by the HIV envelope protein GP 120. CALM3 CXCL 12 GNAQ CCL4 PRKCBl PRKCA
MAPK14CXCR4 JUN CALMl PLCGl CCL2 PTK2B CCR5 SYTl FOS CALM2
MAPK8 cd40Pathway The CD40 receptor is a TNF-type receptor that regulates immunoglobulin expression in B cells and moderates T cell activation via T-cell expression of its ligand. IKBKAP MAP3K1 CHUK NFKBIA IKBKG
MAP3K14 TRAF3 RELA IKBKB TNFSF5 TNFAIP3 NFKBl TNFRSF5
TRAF6 DUSPl cdc25Pathway The protein phosphatase Cdc25 is phosphorylated by Chkl and activates Cdc2 to stimulate eukaryotic cells into M phase. ATM CDC25C CDC2 WEEl CDC25A CDC25B YWHAH CHEKl MYTl cdc42racPathway PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation ofnew actin fibers. ACTR3 WASL ARPC4 CDC42 ARPC3 PDGFRARAC 1 ARPClA
ARPC2 ARPClB PIK3CA PIK3R1 PAKl ACTR2 ARHA j5 cdk5Pathway Cdk5, a regulatory kinase implicated in neuronal development, represses Mekl , which downregulates the MAP kinase pathway. RAFl NGFB KLK2 HRAS MAPK3 CDK5R1 DPM2 NGFR EGRl
MAP2K2MAPK1 MAP2K1 CDK5 cdmacPathway Cadmium 2+ promotes cell proliferation in cultured macrophages by entering the cell via calcium channels and activating the MAP kinase pathway.RAFl TNF NFKBIA PRKCBl HRAS PRKCA RELA
JUN MAPK3 PLCBl NFKBl MAPKl FOS MAP2K1 CUZDl MYC cell_adhesion The attachment of a cell, either to another cell or to the extracellular matrix, via cell adhesion molecules. CCLI l PCDHB 15 KIAA0169 CCL2 TROAP PCDH16 GNE MMRN
EMRl PCDHBI l PTPRF CLDNlO PTPRU TNR ITGB3BP MFGE8 PCDHB12
USH2A NRCAM BAIAPl CNTNAP2 E48 FLJl 0539 GP5 ISLR PSTPIPl
CXCLl 2 TSCl SCARB2 IL8 LPXN CD96 ZYX PCDHA3 RAB13 CD97 HABP2
PCDHBlO SPOCK ALCAM LOXL2 LlCAM F8 CNTN2 TPBG CD226 BYSL
ITGA4 CDH16 NCAMl ITGA5 TGFBlIl DSCAM FAT CD2 CDH 15 PSORSlCl
PCDHB4CX3CR1 PCDHB3 CDH17 IGSFl PCDHB2 MADCAMl IL2 ITGA2 ITGA8
NK4 CHSTlO CDHI l CD151 PNN GPlBA ARHE SEMA5Λ NPHSl APC
GPlBB CLECSF6 PCDHB 14 GACl SPG7 EED SDC2 CNTNl CLDNl
PNUTLl EDGl ITGA9 UNQ429 DSGl SCAM-I CD36 CASPR4 ARVCF HASl CD33
CCR3 DDR2 CCR8 CDH 13 ITGB8 OSF-2 Clorf38 ICAP-IAHNT FPRLl KALI
JUP FEZl MAEA SERF2 DSC2 MCAM LGALS4 ITGB7 CHLl ITGAV CDH8
NEOl ITGB3 CX3CL1 AEBPl RACl ITGB4 CXCR3 DSC3 VWF CDH2 ITGA2B
NEDD9 CASPR3 CNTNAPl PCDHB6 ITGAI l CSPG2 VTN TYRO3 FLJ23042
OPCML CD72 CDON DGCR6 ENTPDl RSl ATP2A2 DDRl SEMA4D PTK2B
NINJl FLOT2 FNl CASK PTPNSl CDSN GPR56 ITGB6 SSPN CDH3 TNC
APBAl CELSRl TGFBI EMILINl SELPLG AOC3 CDH6 BAIl MFAP4 CIBl
ITGAX CD58 CHST4 EFNBl CTNNDl CNTN6 PPFIBPl LGALS7 CD164 ITGAM TM4SF9
SELL NLGN3 CCL4 MLLT4 TSPAN-. I CCL5 CDH4 PAP CTNND2TSPAN-1
LU PLXNCl CD22 PKP4 CCRl ITGAL ITGB2 ITGBLl GP9 NID2 cell_adhesion_molecule_activity OBSOLETE. Mediates the ad lhesion of the cell to • other eel Is or to the ; extracelluli matrix. DSGl MPZ CD36 FGA CD33 CPNEl ZAN GPA33 CDH 13 PCDHB 15
BAIAP2 DCTN6 CTNNBl CD99 OSF-2 FGB DSCl PPFIA2 ILlB PLAU PCDHBI l
MAEA SPN SERF2 DSC2 MCAM PCDH 12 COROl CCPNE3 CHLl NEOl MFGE8
PCDHB 12 NRCAM PPFIAl E48 VCAMl DSC3 VWF CDH2 GP5 PCDHB6
THBS2 OCLN NINJ2 VTN TYR03 OPCML CEACAMl DGCR6 ZYX ENTPDl
PECAMl PCDHA3 DSG3 ICAMl NINJl PCDHBlO ALCAM SELP ICAM2 LlCAM
FLOT2 CNTN2 ICAM3 FNl CD226 PCDHl IX BYSL CDSN NCAMl LY9
ICAM5 CD6 SELE DSCAM CDH3 PCDHl FAT TM4SF8 CD2 CDHl 5 CEECAMl
PSORSlCl EMILINl I PCDHB4EVA1 ICAM4 PCDHB3 CSPG4 IGSFl DPT
PCDHB2 CIB1 PKP3 NK4 MPRA CD58 CD151 PNN PKPl ARHE TM4SF6
CD164 PCDHB14 FGG SELL SPG7 FI lR FEZ2 PAP CNTNl THBSl
THBS4 CDHl LU CD22 GP9 UNQ429 CCL3 cell_adhesion_receptor_activity OBSOLETE. Combining with cell adhesion molecules to initiate a change in cell activity. MADCAMl ITGAE CRTACl SELP MDS028 ITGB3 ITGA2 ITGAX ITGA8 ITGB4
TNFAIP6 ITGBl ITGA4 FLJ10539 ITGB8 ITGA2B ITGA7 ITGA5 ITGB6
ITGAM ITGA6 ITGAl 1 ICAP-IA FLRT3 ITGAlO TNC CDA08 ITGA3 ITGB5 BBS2
ITGAL ITGB2 ITGBLl DKFZP761D0211 DAGl ITGB7 ITGA9 ITGAV
Cell_Cycle The progression of biochemical and morphological events that occur during nuclear or cellular replication. E2F2 CDK6 MADH4 MAD2L1 HDAC4 ESPLl ORClL CCNB2 CCNH HDAC2
PRO1073 MCM5 E2F3 MCM6 LOC51270 CHEKl PRKDC MAD2L2CDC6
HDAC7A ABLl GSK3B BUB3 ORC5L CDC25A CDC25B CDK2 SMClLl ORC6L
MCM4 E2F6 CCNEl BUBlB HDAC5 MDM2 TP53 CDKN2Λ CDC14A PKMYTl
CHEK2 ITMl HDAC6 CCNE2 MCM2 ORC4L TGFBl ATM ORC2L CDC45L MCM3
TFDPl PTTG2 PTTG3 MADH3 E2F5 CCND2 CDC25C CCNAl E2F4 GADD45A
WEEl HDACl SKP2 CDC20 HDAC3 MADlLl MCM7 CDKNlE I E2F1 HDAC8
BUBl CCNA2 PCNA CDC7 CDC2 CDK4 CCNBl RBl 0RC3L PLK CCND3
PTTGl CDKNU YWHAG cell cycle arrest Any process by which progression through the cell cycle is halted during one of the normal phases
(G1, S, G2, M). EIF4G2 GAS7 CUL5 MAP2K6CUL4A CUL2 IFNWl GADD45A CDKN2D
PPP1R15A C10orf7 CPR2 CUL3 GASl CDKN3 MYC CDKN2C CDKNlB
KHDRBSl MAPK12CUL1 RPP14 CDKNlC PPMlG PR48 GMNN MLLT7
SESNl CDKN2A AIFl CDKNlA PLAGLl REPRIMO PCAF CDKN2B cell_cycle_checkpoint A point in the eukaryotic cell cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage. ATM HUSl MAD2L1 TIMP3 RAD17
MSH3 GADD45A MCM6 RAD9A CHEKl RPAl LCMT2 BRCAl ABLl MCM7
RP A2 NBSl MCM4 MREl IARP A3 RAD50 GAPD TP53 CHEK2 MXD3 RAD51 cell cycle checkpointll GO TP53 CCNG2 CDKN2A RBl NBSl CDC34 CCNE2
FANCG ATR RBBP8 cell_cycle_regulator OBSOLETE (was not defined before being made obsolete). MPHOSPH 10 CDC45L
CDK6 ZRFl CDC37 PRKR BTG2 MPHOSPHl MCM5 WEEl 101F6 SPIN
BTGl CDC6 CDKNlB BCL2 MPH0SPH9 CDK7 MPHOSPH6 CHESl
YWHAQ CDK5R1 RGC32 SRPKl CDKNlA CDK5 cell_death Activation or halting of cellular processes so that vital functions markedly cease, culminating in cell death. RRAGA EIF4G2 OPTN EMP3 APP CLULl EMP2 PTGER3 ILl 7 EVIl EMPl
FOSL2 CLU cell_growth_and_or_maintenance The processes pertinent to the integrated function of a cell. FLJl 0305 QSCN6 DACH2 TRPMl RASDl EXTl RHCG DNAJA3 SMO ADPRT HMG20B GPC3 PPAP2B LECTl TACC3 EIF3S6 KIAA0052 GEM CTGF EXTLl PLAU
COL5A2 FGF5 GNA12 IL6R DACH MTMl CLN5 ANGPT2 JAK3 TFFl DRG2 PRSSI l NFl GPR74 EXT2 DTNA MXD4 HPN IRF5 GATA2 IER3 GAS2 ERBB2 SUIl DUSP12 EVIl INSR LGALS7 OS-9 SKIL PRDMl CXCLl CDRl DDXl RANBP9 CCL4 GAS2L1 PCOLCE LIMDl GPC6 PPAP2A JAZ INHBA EXTL3 STMNl SKI SEMA3CDDX26 FOS EDFl cell_motility Any process involved in the controlled movement of a cell. IL13 FLNA JAK2 ARFIP2
THBS3 COROlA KPTN NTF3 MSTlR PTGS2 FPRLl ARPC5 IFNG KALI
HRAS GNA13 ANXAl PAFAH1B2 LSPl WASL NEOl PAK4 TXN CAPZAl
PALM IL8RB F2R CRK RACl FPRL2 LIMKl TNFRSFl 2 A SERPINI2 CXCR3 CXCLlO PAFAHlBl MAP2K1 ACTR3 MARCKS FLJ23042 IL8
CRKL PECAM IAAMP MSN LTB4R VNN2 CD97 ADRA2A SPOCK HMMR
MAPK14HGF TPBG FNl KIAA1522 DNALIl VNNl OR1D2 PYY UBE3A
ACTR2 SEMA3EFLJ10211 CTGF ACTN4 TM4SF8 NTNl AKAP3 WASFl CEECAMl
SPINT2 MMP12 IGFl ARPClB BCL9L AMFR CSPG4 BLRl FPRl MAPK8 C3AR1 AKAP4 ARPC4 CHST4 KATNBlNPY NOS3 CAPZA2 HGFAC TM4SF6 DNAH5 MKLNl
STAT3 TM4SF9 SELL ENPP2 SERPINB5 Fl IR DNAH8 CCL4 ARPC3 YARS
TSPAN-2 CCL5 ARPC2 THBSl THBS4 VASP TSPAN-I XLKDl CSPG3
ITGAL MIR HUMAUANTIG DNAH9 CCL3 ACTB cell_proliferation The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. CKSlB CDK6 CBFA2T2 TCF8 Cόorfl 08 CTNNBIPl ISG20 REGL PDAP2
CDK9 PIM2 VTIlB GPC4 CHRMl BUB3 MNT CTFl CRIPl DD5 ADRAlB RPS4X PDAPl ZNF 187 ERF CDC27 EVI5 TACSTD2 CHRM4 DTYMK ERG
SYK CYR61 TXN OSMR MS4A1 EMP3 CHRM5 USP8 INSL4 IL2RG TCF19 IL9R PDCDlLGl SKBl BTGl KHDRBSl RPP14 BST2 BUBl UHRFl RPS27 TGFA SIPAl ELN TRIP EMPl SPOCK TGFB2 CKS2 MET PYY
ELF5 PTCH FSCNl ENPEP RBBP7 PRKCA IRF2 CDK7 STAT6 ARHGEFl BUBlB EPS8 MKI67 KRT16 PRKCM CDC14A BS69 EGFR LRPAPl TFDPl IGFBP4 CUL5 TPX2 ILIA FTHl LATSl CDK3 EPHB4 CSFl CSElL KIF2C SERPINFl PRL PDZKl PRG4 CDC2L2 PCNA IL3 FES TNFRSF9 AKRl C3 SFN CDK4 KNSL7 THPO UNQ429 CDK5 IL13 C8FW HDGF PRDXl GFIlB BLZFl
DUSP22 IL5RA CD81 MT3 CDC16 MYC ERBB4 MASl NAB2 TM4SF1 ILlB NUDC TIEG FGF5 LGIl APRIN EDNRA HDGFRP3 IL6R LAMAl CD160
LRPl FZD3 GRPR IL8RB BCARl GABl TSPY ERBB2 ZFP36L2RFP OSM AREG BCATl GSPTl PEMT RAFl MADILI MNATI MAD S100A6 CDK5R1 TNFRSF 17 APPL SLC29A2 ILI l GCG PTHLH MATK EHF IL6 CD28 PRDM4
EPAC TCFL5 PDGFRAHGF IL4 PSPHL EMP2 ZNF259 SIL CLKl TPD52L2 NDP IL2RA BINl DKCl CREG IL12B REGlB KITLG TM4SF8 GRN TGFBI NR6A1 TNFSF13B EPS15 TALI MYT2 MTCPl PLEKHCl LAMP3 SlOOB
TNFSF8 IL15 PDGFA LMOl CDC25C TNFSF9 NPY MAPREl LY86 MIA SKP2 UBE2V2 CXCLl TM4SF9 TNFSF7 MPL INSIGl E2F1 CCKBR MAPRE2IL15RA IL12A
DAB2 TSPAN-2 PAP CBFA2T3 TSPAN-I CXorfl5 E4F1 PLK
CSFlR DCTN2 FGF6 PTEN cell_surface_receptor_linked_signal_transduction Any series of molecular signals initiated by the binding of an extracellular ligand to a receptor on the surface of the target cell. FLNA DOKl STCl PIP5K2BASGR2 AGER DRD4 C21orf4 LILRB2 OXTR TRPVl DOK2 PTPRC RAMP2 8D6A CCL2
BIRC2 CCL25 KLRFl GALR2 TNFRSFlOB IL17C GEM BIRC3 CSF3 WSXl IFNG CTFl HRAS KLRDl RAMP3 MERTK SAG MKNK2 BRD8 IL6R LLTl FLJ38628 LILRB3 PLCG2 TACSTD2 ANXAl CCR5 CHRM4 KLRAl ARHGEF2
TNFRSF14 CD160 GLRA2 KLRGl OSMR IL8RB ADCYAPlRl BAIAPl INS CXCLlO IFNAR2 IL7R MARCO NTSR2 STC2 MYD88 INHA CLC PDCDlLGl
ADRB2 RRAGA LILRBl AGT LY6E IL12RB1 ILl 2RB2 ILl 8RAP HRMTl L2 IFNARl
EDNRB CLEC2 CD97 LIFR CENTAl ILlRl IL6 CD28 SIRPBl IFNA2 GIPR PDGFRATACR3 NPR2 MAPK14ECGF1 HGF IGSF2 IL6ST IL8RA IFNGR2 CLECl AGTR2 IL2RA GLRB PRKCA IL13RA1 IFNBl MADD TNFRSF13B CD79A FLJ32356 BDKRB2SSTR1 MS4A3 KLRBl SST CD19 C5 GLRAl ADMR LIF CD14
CSF2 PDGFA HCST ISGF3G GPlBA LEPR P2RY1 CD3D GPlBB PRL CLECSF6 MPL CD59 CCKBR TTRAP IGSF6 FADD BSG CD4 LY96 CD69 PNUTLl
CSNKlAl CCRl TNFRSF25 IRAK3 BAGl cell2cellPathway Epithelial cell adhesion proteins such as cadherins transduce signals into the cell via catenins, which alter cell shape and motility. ACTN3 PTK2 ACTN2 BCARl VCL PXN CSK PECAMl ACTNl
CTNNA2SRC CTNNBlCTNNAl cellcyclePathway Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CDKN2C CDKNlB E2F1 TFDPl CDK6 CDC25A
CDK7 CDK2 CCND2 CCNAl CDC2 CCNEl CCNH RBLl CCNDl CDKN2A
CDKN2D CDK4 RBl CCNBl CCND3 CDKNlA CDKN2B ceramidePathway Ceramide is a lipid signaling molecule that can activate proliferative or apoptotic pathways, depending on signaling context, localization, and cell type. RAFl MAP2K4TRAF2 TRADD MAP3K1 BCL2 FADD
TNFRSFlA SMPDl RELA MAPK3 CYCS BAD BAX PDCD8 NFKBl RIPKl
MAPKl CASP8 NSMAF MAP2K1 MAPK8 cftrPathway The cAMP-regulated chloride channel CFTR (deficient in cystic fibrosis) is regulated by the surface- localized beta-adrenergic receptor. ADRB2 ADCYl PRKACG PRKAR2A CFTR SLC9A3R1
PRKARlB PRKACB GNAS VIL2 PRKAR2B PRKARlA chemicalPathway DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. EIF2S1 ATM CASP9 BCL2 PTK2 PRKCBl
PRKCA PXN CASP6 AKTl CYCS STATl TP53 CASP7 BAD CASP3 ADPRT
BAX TLNl BCL2L1 BID APAFl chrebpPathway Carbohydrate responsive element binding protein (chREBP) is a transcription factor inhibited by cAMP and activated by high carbohydrate levels. PRKAR2A PRKACB GNGTl PRKAR2B
PRKARlA BGl PRKAG2PRKAA2 BUCSl ADCYl PRKACG PRKARlB
PRKABl WBSCR14 GNAS PPP2CA GNBl PRKAGl PRKAAl PRKAB2 circadianPathway A heterodimer composed of Bmall and Clock acts as a transcription factor for proteins that regulate circadian rhythms, such as Per and Cry. CRY2 PERl ARNTL CRYl CLOCK CSNKlE cklPathway Caseine kinase 1 (CKl) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway.
PPPlRlB PRKAR2A GRMl DRDl PRKACB PRKAR2B PRKARlA
PLCBl CDK5R1 PRKACG PPPlCA PRKARlB PPP2CA CSNK1DDRD2 PPP3CA
CDK5 classicPathway The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C2 ClQB ClQG C5 C8A
ClQA C3 C4B C9 ClR C7 CIS C4A C6
Complement_Activation_Classical Processes involved in the classical complement cascade, which promotes microbial lysis, disposal of immune complexes, and regulation of other immune processes. C2 ClQB ClQG
MGC2198 DAF C5 C8A ClQA C3 C8B C9 C7 MASPl
CIS C4A C6 compPathway Both the classic and alternative immune complement pathways promote inflammation, foreign cell lysis, and phagocytosis. MBL2 C2 MASP2 ClQB ClQG C5 C8A ClQA C3
C4B BF C9 ClR C7 DF MASPl C4A CIS C6 cptPathway BLACK CPTlA CPT2 ACAS2 SLC25A20
CR ANGIOG PNAS 2001 ANGPTL2 THBSl VEGFB BAIl FLTl FLT4 KDR
ENG PECAM IVEGF
CR CAM PNAS 2002 DSGl ITGAE HMMR ALCAM SELP ICAM2 TIMP3 ICAM3
FNl MMP9 ITGBl BYSL GPA33 ITGA4 CDH 13 NCAMl ITGB8 TIMPl ITGA5
CD99 SELE CDH3 PCDHl FAT PTK2 SDCl TNC ARHGAP6 JUP
CDH 15 SELPLG ITGA3 TNS TIMP2 CDH6 ROCKl NCAM2 ARHGAPl ITGB5
MCAM CDH7 ITGAl PTPRU CDH17 ITGB7 ITGAV WASL NEOl ITGB3 ITGA2
CDH 18 CDH12 ITGAX CD44 MMP 13 CDH5 F2R RACl CD58 CDHI l ITGB4
SERPINI2 CXCR3 MMPl VCAMl DSC3 PKPl ITGA7 CDH2 ADD3 BPAGl
ITGAM CXCLl 2 CD47 SELL SERPINB5 ANKl CEACAMl IL8 MMPI l
ZYX CDH4 PECAMl GJB2 GJA4 CNTNl CDHl SEMA4D CD97 ICAMl
DCC PKDl ITGB2 ITGAL ITGA9
CR CANCER TESTIS PNAS 2003 BAGE MAGEAlO SSX2 MAGEA8 MAGEA12
TESKl CTAG2 MAGEE 1 MAGEA9 SSXl MAGEA3 GAGEl
CR CELL CYCLE PNAS 2004 CDC2L5 E2F2 HUSl FOSLl SKPlA CKSlB ERH
CENPE CDK6 CKS2 MAD2L1 ORC1L BTG2 CCNH CDK8 MYBL2 POLR3D FRK
CENPCl CHEKl CDCl 6 MYC MXIl CDC6 BUB3 CDC42 CDC25A CDC25B CDK7
CDK2 CHESl NUMAl TP73 TFDP2 CCNEl BUBlB MDM2 CDC27 TP53 CDKN2A
CDC14A RBBP2 DDXI l CCNE2 CDKN2B CDC45L MAX ZWlO CENPA GAS2
CDC37 CCND2 CDC25C CCNDl BCCIP SKP2 CPR2 GASl TTK GSPTl CDC20
MADlLl CNK MNATl CDKNlB CENPF MAD E2F1 BUBl CDKNlC
CCNA2 CCNF CDC7 CDC2 CDC2L1 RBLl GADD45B CDK4 CCNBl RBl
PLK MOS CCND3 CDKNlA NPMl CDK5
CR CYTOSKELETON PNAS 2005 FLNA MAPlB GSN MYL2 VIM PTCH CETNl
TUBAl PFNl BPAGl RSN TUBA2 EMSl KISSl SPTB ACTGl MYL3 VCL MUCl MAPT MSN TTN TTLLNNll SPTAl MCF2
CR DEATH PNAS 2006 BIK TTNNFFRRSSFlOD CASPl DAPKl TRAF3 CASP6 CRADD
ILl 7 CASP7 CASP3 GML BBAAGG44 CFLAR NME3 TP53BP2TNFRSF10B MYC
MXIl TNF T TRRAAFF22 BBCCLL22 BBBCCCLLL222/AA11 TTNNFFSSFFllOI 3 BBAAKKll TTFFPPTT DDPPFF22 TP73
MDM2 TP53 LLTTBB TTPP7733LL TTTNNNFFFRRR!SSFF6i 6 DDAAXXXX BBCCLL22LL11 BBIIDD LLTTAA HRK
CIDEA CASP9 MMAAXX BBNNIIPP22 FFF222RRR BBFFAARR PPAAWWRR AAAATTFF BBNNIIPP33 DDAAPPKK3: DAP3
EVIl BAX CCAASSPP88 MMYYDD8888 BBNNIIPPll CASPlO TNFSF7 CASP4 TRADD MAD IKBKG
FADD CASP5 TTNNFFRRSSFF9 9 SSTTKKll 77B BAD DAP BCL2L2 TNFSF5 EMPl
TNFRSFlOA SSTTKKll 77AA . CCAASSPP22 PPLLAAGGlLl TNFRSF25 TNFSF6 FOSL2 APAFl
CR DNA MET AND MOD PPNNAASS 22000077 DNMT2 CHCl HMGAl TERT OASl LIGl
TK2 MCM4 MMBBDD22 SSllOOOOAAII ll NNMMEE66 RFC3 TEPl ADK POLB MLL TERFl
LIG3 DNMTl HHMMGGAA22 TTEERRFF22IIPI >MMBBDD44 RFC4 PCAF
CCRR. HORMONAL , FUNCTIO )NNSS PPNNAASS 220 00088 ESRl HSD17B2 NNKKXX33--11 FFSSHHRR THRB
GIP STAR P PGGRR AADDRRBBKKl 1 THRA BAGl SSSSTTRR22 CR IMMUNE_FUNCTION P PNNAASS_ 22 000099 IILL1133 CD36 CD33 IILL44 MMIICCAA IILL66SSTT ILl 7
CD68 CD24 TFE3 FCGR2B IFNG CD2 ILlB IFNBl HCAl 27 CD48 CD37
CD8A GAGE4 LAG3 ILlO IFNAl IL18R1 SLAMFl CD19 IL16 CD53 MAGED2
CD58 NKTR CD63 ILl 5 CD14 IFNAR2 CDlD IFNGRl BAGE CD47 CD59
IL2RB CD7 ILl 2RBl CD72 CD4 BTK CD69 IFNARl CD34 HLA-C CD9
CD97 CTAG2 CD22
CR PROTEIN MOD PNAS : 2010 PDK2 HDAC4 PRKCLl PTPRC PRKGl PTPRM NAT2
RYK PRKACG CTSD MME HCK PRKCZ RPS6KB1 EP300 PIMl
PDPKl TESKl PPP2R3A PRKCL2 PTPRD PTPN12 ABL2 HDAC5 PIK3CA BLK PTPN6 PTPRF PTPRK HDAC6 PRKAGl PPEFl DUSP8 HPN PTPN7 PPPlCC TBCC PRKCBl LTK PRKARlA PTK9 LIMKl PPP2R5A ACP5 SIATl PTPN9
PTP4A1 RAGE CSNKlE USP4 LYN PTP4A2 PRKCG STKI l CSNK2A2 USP6
PPP2CA DUSP7 PAK2 MATK USP5 LIMK2 PRKCI PPMlD ST13 PTPN18 FURIN YESl LCK CTSB PRKR PPP4C RPS6KA2 IL3RA FER FGR DPP4
UBE2N PTPRR PRKACA PRSS25 BMX PPP1R3A PRKDC ABLl PRKACB
CHUK CULl PRKCA PPPlCB DUSP9 PHKG2 TMPRSS2 PAPSSl VHL PRKARlB
PRKCM DUSP5 DMPK PPP2R4 PTK7 PDK4 PTPNI l CSNK2B PPP2R1B PTPN4
PRKAR2B DUSP3 PTPN2 CUL2 ELK3 PTPRZl UCHL3 PTPNl PTPN13 ACPP
CSNKIDPTPRG BCR PPP3CA PRKCQ PPP5C PPP3CB DUSP4 KIT PTPRH STK3 ACP2 PPP2R2A FES PPP2R5D STK4 PPP6C ACPI PTPRB PPPlCA
ANPEP SKI PTPRN2 CSNKlAl PRKG2 PPP2R5E PTPRN UBE2I PTPRA
ELKl PCAF PTPN3 PHKA2 PPP2R5B
CR REPAIR PNAS_2011 FENl DDBl ERCC5 ALKBH EXOl RAD51L1 XPA
FRAPl BRCA2 APEXl RAD17 MSH3 ADPRT RAD54L OGGl XRCC3 RAD9A RAD23A
BRCAl PMS2 POLDl RAD52 MSH6 ERCCl PMSl XPC XRCC5 MLHl PCNA
G22P1 CKNl ERCC4 RAD50 RAD23B RAD1 MSH2 ERCC3 PIR51 CHEK2 RAD51 DDB2
CR SIGNALLING PNAS_2012 TANK WNT5A ILK CALMl MAP3K8MAP3K7IP1 SUFU
IL17 ARHGEF12 ITGA6 PDPKl FLT3LG ARHGAP6 MAPK7 TYK2 GPRK6
ABL2 MAP2K2ARHGAP1 DGKQ PTPRK ERG SYK FYN AKAP13 MAP3K3
NOTCH3ARHC IFNAR2 MAPK4 ITGA7 MYD88 M AP2K I CXCL 12 NOTCH4 IKBKG AXL
IL8 IFNARl TRIP MAP3K4MSF ARHB RALBPl ARHA MAP2K6IL6ST MCC
ITGA4 PTCH ITGA5 ABLl NRAS STAT5B STAT6 ARHI MADH7 ITGA3 NFl
ARHGEF16 SRC GNBl ITGAl IL18R1 ATM ITGA2 IGFBP3 NCKl APC
APCL STAT3 SKIL TTK BCR TNFSF13 SH3BP2 BRAF BTK TNFRSF4
SFN MAP3K12 MAPKl TNFRSFlOA ITGA9 ITGAE IL13 TNFRSFlOC
TRAF3 RELA MAPKl 1 ITGB8 BIRC2 CTNNBl IRSl RGS16 MAP2K7 TNFRSF 1OB
MASl RAPlA TNF ARAFl DLGl AKT2 IGFBPl IFNG MKNKl ILlB HRAS
MAP3K14 TNFSF4 MADH2 JAK3 TNFRSF14 ILlO ITGB7 ITGAV ZAP70
STAT5A ITGB3 VAVl PIK3C3 TNFRSFlA VIPRl CRK YWHAE ITGB4 AKTl
TNFRSFlB STAT2 INHA DGKG IFNGRl RAFl DGKA IL2RB TYRO3 MUSK
MAPK12IL12RB1 RAN CRKL CAMK4 MAPK9 JAKl STATl TIAMl PTCH2 GRB7 TRAFl PTK2B GRF2 PIK3CG WNT4 MADH4 ROSl WNTl ITGBl GRB 14 SMO WNT2 TRAF6 RHOK MAPK13JAG1 IFNBl AXINl ROCKl CMKORl MAP3K5 AXIN2 MAPK10ITGB5 RELB JAG2 ITGAX SOSl CXCL3 IL15 MAP4K4IQGAP2
SHCl ITGAM MAPKAPK5 CXCLl MPL BCLlO MAP2K4KRAS2 RASAl CXCL2 MAP2K3IRS2 REL MAPKAPK2 ITGB2 ITGAL MAP2K5PTEN
CR TRANSCRIPTION FACTORS PNAS 2013 PPARA HKR3 EGR3 GLI FOSLl FLIl
NMEl RELA WTl PAX7 ETVl MYBL2 PBXl IRF4 EGRl FOXD2 MYBLl AHR ZNFNlAl MYODl ETSl MYC GAS41 MYB STAT5B JUND TIEG
CBFB STAT6 CHESl DPF2 TCF7L2 MLLT7 SMARCA4 SPIl RELB PML GLI3 CBFA2T1 MYCN MAFG BCL6 STAT5A JUNB FOSB MADH3 RUNXl JUN ETV6 AATF MAF LMOl CEBPA PBX2 ETS2 NFKB2 STAT3 ETV3 FOXDl FOXFl RXRA SRF GLI2 CBFA2T3 TLXl REL ATFl LITAF EHF FOS FOSL2 CR_TRANSPORT PNAS_2014 SLC22A1L NUP98 ABCC4 NUP214 TPR KPNBl SLC14A1 CR_TRANSPORT_OF_VESICLES PNAS_2015 RAB7 RAB27A PIK3C3 RAB26 RAB27B AP2M1 AP3D1 RABlA RAB4A RAB2L RAB31 MEL RABl IA RAB33A RAB3A ACTR1ARAB5C RABlO RAB2 RAB3B RAB7L1 RAB5B RAB13 RAB5A GOLGA4RAB6A crebPathway CREB is a transcription factor that binds to cAMP-responsive elements (CREs) to activate transcription in response to extracellular signaling. CAMK2D PRKAR2A SOSl PRKCBl
MAPK14RAC1 PRKAR2B MAPK3 PRKARlA AKTl ADCYl PRKACG
PIK3R1 PRKACB CAMK2G PRKCA CAMK2A GRB2 HRAS CAMK2B
PIK3CA PRKARlB RPS6KA5 CREBl GNAS MAPKl RPS6KA1 cremPathway The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCYl FSHB FSHR FHL5 XPOl GNAS CREM cskPathway Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. TRB@ CD3E PRKAR2A HLA-DRA CD3Z
ZAP70 GNGTl PRKACB TRA@ LCK PRKAR2B CD4 PRKARlA
PTPRC CSK PRKACG ADCYl CD3G PRKARlB GNAS GNBl CD3D
HLA-DRBl CREBBP ctla4Pathway T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APCs CD80 or 86. CD3E TRB@ IL2 HLA-DRA
CD3Z PTPNI l ICOS CTLA4 GRB2 TRA@ LCK ICOSL CD86 PIK3CA CD3G
PIK3R1 ITK CD80 CD3D HLA-DRBl CD28 ctlPathway Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. TRB@ CD3E CD3Z TRA@ PRFl GZMB CD3G
HLA-A ICAMl TNFRSF6 CD3D ITGB2 ITGAL TNFSF6 B2M cxcr4Pathway CXCR4 is a G-protein coupled receptor that responds to the ligand SDF-I by activating Ras and PI3 kinase to promote lymphocyte chemotaxis. RAFl PIK3C2G CXCL 12 GNAQ GNAIl GNGTl
PTK2 HRAS PRKCBl PRKCA BCARl CXCR4 CRK PXN RELA MAPK3 PIK3CA
PIK3R1 PLCGl PTK2B NFKBl MAPKl MAP2K1 GNB1 cytokinePathway Intercellular signaling in the immune system occurs via secretion of cytokines, which promote antigen- dependent B and T cell response. IL13 TNF IL2 IL12B IL16 IL9 IFNG IL5
IL8 IL12A IL4 IFNBl ILIA IL3 IL15 IL18 IL17 IL14 IL6
IFNAl ILlO LTA d4gdiPathway D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. CASP9 CASP 1
ARHGDIB JUN CYCS PRFl GZMB CASP3 ADPRT CASP8 ARHGAP5
CASPlO APAFl dbpbPathway BLACK NSEPl PROCR PDGFB F2 dcPathway Dendritic cells internalize and present antigen, after which they migrate to lymphocyte-rich tissues and induce T and B cell differentiation. ILl 3 ILl 2B TLR9 IFNG ITGAX CD7 CD2 IL5
TLR4 CD33 ILl 2A IL4 IFNBl IL3 CSF2 CD5 ANPEP TLR2 TLR7
TNFRSF5 IFNAl ILlO deathPathway Death receptors such as Fas and DR3, 4, and 5 transduce pro-apoptotic signaling by oligomerizing to activate the caspase cascade. CASP9 NFKBIA GAS2 RELA CASP6 CASP3 CASP7 BIRC4 BIRC2
CFLAR RIPKl CASP8 CASPlO TNFRSFlOB LMNA TRAF2 BIRC3 TRADD BCL2
CHUK SPTANl FADD TNFSFlO MAP3K14 CYCS DFFB NFKBl
TNFRSFlOA TNFSF 12 TNFRSF25 DFFA BID APAFl
MAGE SIGNALLING GO HUSl GTSEl FENl ERCC5 TREXl BTG2 XPA
PURA APEXl BIRC2 RAD9A RAD23A CHEKl LGMN BRCAl PMS2 TNFRSFlOB
UNG TNF CDC6 PRKDC PTPRCAP RAD52 BBIIRRCC33 CDC25A XPC CDC25B
MLHl CKNl BAKl LIG4 TNFSF4 ERCC4 DKFZP566E144 MDM2 TP53 PINl
RADl ATRX MSH2 ERCC3 CHEK2 TNFRSF6 RRM2B RAD51 XRCC2 ERCC2
ATM BCL6 DDBl XRCCl RPL13A H2AFY BNIP3 CDC25C BRCA2 RAD17 MSH3
LRDD GADD45A WEEl CDKN2D BAX BBC3 ARTN PPIA FOXO3A
CDSl CDC20 XRCC4 TERT MSH6 REV3L ERCCl H2AFZ XRCC5 PCNA MREI lA
MPG SRPX ATR RAD50 RAD23B GADD45G GAPD TNFRSF4 SESNl
GADD45B CDK4 CDKNlA REPRIMO PPMlD APAFl DDB2 ACTB dnafragmentPathway DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. HMGB2 GZMB DFFB ENDOG CASP7 CASP3 TOP2B TOP2A HMGBl DFFA dreamPathway The transcription factor DREAM blocks expression of the prodynorphin gene, which encodes the ligand of an opioid receptor that blocks pain signaling. PRKAR2A PRKACB PRKAR2B
POLR2A JUN MAPK3 PRKARlA OPRKl PRKACG PRKARlB CSEN
CREBl FOS CREM drug_resistance_and_metabolism BioCarta GSTPl EPHXl CYP2B6 ABCCl CYP2E1 SODl NAT2
TPMT TOP2B TOP2A AHR TYMS BRCAl RXRG MYC ERBB4 CDK2 CYP3A5 PPARGCl TOPl CCNEl ABCC5 TP53 DHFR MSH2 ERCC3 ABCBl BCL2L1 TNFRSFI lA ERBB3 EPHX2 CRABPl ERBB2 GSTMl CCNDl GSK3A CDKN2D
PPIA RARB CDKNlB STE MGMT CYP2C8 ; RXRB RBl RARG SRD5A2
CYP2C9 PPARA ABCC3 IGFlR IGF2R ABCC2 RARA XPA MET PPARG NFKBIB
CRR9 BCL2 XPC MLHl ABCC6 PPARD CYP2C19 HIFlA BLMH CDKN2A
RELB CYP2D6 ATM ESRl EGFR COMT ESR2 RPL13A FGF2 BRCA2 MSH3
CYP3A4 ABCG2 BAX MVP NQOl CYP 1A2 APC NFKB2 CYPlAl RXRA NFKBIE
APlSl AR ARNT GAPD CDK4 NFKBl FOS CDKNlA ELKl ACTB ecmPathway Extracellular matrix induces integrin-mediated FAK phosphorylation in epithelial cells, leading to PI3 and MAP kinase activation and actin reorganization. RAFl PTK2 HRAS PXN GSN MAPK3
DIAPHl MYL2 ROCKl ITGBl MYLK PIK3CA PIK3R1 TLNl MAPKl SRC ITGAl
MAP2K1 SHC1 ARHGAP5 PFNl FYN ARHA edgl Pathway The lipid SlP is an EDGl ligand promoting chemotaxis via Racl and cell survival and proliferation via ERK activation. SMPD2 ITGB3 GNGTl PRKCBl PDGFRA SMPDl RACl MAPK3 AKTl PDGFA
ADCYl PIK3R1 GNAIl PTK2 PRKCA PLCBl SPHKl ASAHl PIK3CA EDGl MAPKl
SRC GNBl ITGAV SKIP ARHA eeal Pathway The FYVE-finger proteins EEAl and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EGFR TFRC RAB5A EGF HGS TF EEAl
EGF_receptor_signaling_pathway BioCarta EGFR SHC3 NAP4 EGF GRB2 GABl EPS 15
EREG EPS8 GRB7 SHCl NCK2 PYGO2 REPS2 egfPathway The epidermal growth factor (EGF) peptide stimulates the EGF receptor to promote cell proliferation via the MAP kinase and Ras pathways. EGFR STAT5A SOSl PRKCBl M APK3 JUN PIK3R1 PLCGl
MAP2K1 SHC1 STAT3 RAFl MAP2K4 RASAl MAP3K1 SRF EGF PRKCA GRB2
HRAS JAKl STATl PIK3CA CSNK2A1 FOS ELKl MAPK8 egfr_smrtePathway EGF receptor activation inhibits SMRT, a transcriptional co-repressor that interacts with transcription factor complexes and gene silencers. EGFR RXRA THRB MAP3K1 EGF MAPK14MAP2K1 NCOR2
RARA THRA ZNF145 Eicosanoid_Synthesis BioCarta PLA2G6 PTGDS PTGS2 LTA4H AL0X12 ALOX15B PTGIS
ALOX15 PLA2G2A TBXASl AL0X5 AP AL0X5 LTC4S PTGSl DPEPl eif2Pathway Eukaryotic initiation factor 2 (EIF2) initiates translation by transferring Met-tRNA to the 4OS ribosome in a GTP-dependent process. EIF2S1 HRI GSK3B PPPlCA EIF2AK4EIF5 EIF2S3 EIF2AK3
EIF2B5 EIF2S2 PRKR eif4Pathway The eIF-4F complex recognizes 51 mRNA caps, recruits RNA helicases, and maintains mRNA- ribosome bridging. EIF4G2 PABPCl PDPKl GHR MKNKl PRKCBl PDK2 PRKCA MAPKl 4MAPK3
AKTl EIF4G1 EIF4E FRAPl EIF4A1 PIK3CA PIK3R1 EIF4EBP1 MAPKl EIF4G3
EIF4A2 IRSl PTEN RPS6KB1 electronjransport BioCarta CYP4A11 CYPI lAl CYP39A1 CYP7A1 PTGIS CYBRDl
CYP2B6 CYP2E1 CYP2C18 CYP19A1 FADS2 CYP27B1 CYP8B1 TSAP6
HCCS CYP7B1 FADSl FLJ20359 CYP24A1 CYP2A13 CYP2S1 CYB561
UQCRB SMOX SCO2 FADS3 FRDA UGDH FLJ32499 CYPlBl CYB5 DHODH EIF2AK3SCO1 CYP3A5 CYP4F11 CYP2J2 CYP51A1 STEAP2 PGRMCl
MAOA CYP20A1 CYP2D6 MGC32124 CYP21A2 MGC20446 CYP 17Al
CYP4B1 CYB5-M CYP11B2 CYP4F12 CYP26A1 CYP27A1 PAOX
UQCRH CYP3A4 TBXASl NUP62 SUOX CYP 1A2 ERNl OXAlL MAOB CYPlAl SPUF CYP4F8 SURFl NCB5ORCYP3A43 AOFl P450RAI-2 FDXR CYP4F3 PGRMC2
CYP2C8 CYP2A7 CYP2F1 CYP2A6 ALAS2 CYP46A1 KIAA0090 FLJ23153
UQCRC IPPOX CYP3A7 CYP2C9 CYP4F2
Electron_Transport_Chain BioCarta QP-C ATP5J2 NDUFS2 NDUFC2 NDUFA 10 ATPIFl UQCRFSl NDUFB8ATP5J NDUFA2SLC25A27 UQCRC2NDUFB6UQCR NDUFABl COX 15 NDUFB7ATP5S ATP5C1 COX5A UQCRB COX6A2NDUFA6ATP5I NDUFS7 NDUFB4NDUFC1 SALL3 SCOl COX5B COX7A1 ATP5B CYCS NDUFS8 NDUFB9 LALPl UCP3 AFG3L2 ATP5G3 ATP5O SDHD UCP2 NDUFA5NDUFB10 ATP5F1 ATP5G2 NDUFB2COX7A2L
ATP5A1 NDUFA7NDUFB5ZNF183 NDUFSl SLC25A5 COX8 UQCRH COX6C NDUFA8 SDHB NDUFB3 SLC25A6 POPDC2 NDUFS4 NDUFA9SLC25 A14 COX4I1 ATP5L
NDUFS6 COX7C COX6 A I NDUF V ITBDN 100 UCPl NDUFBl DAP13 NDUFA3COX7A2
SURFl ATP5H NDUFS5 ATP5G1 SDHA NDUFA4COX7B NDUFV2SDHC NDUFS3 COX6B HSPC051 UQCRCl COXI l ATP5E LOC339231 SLC25A4 ATP5D electron_transporter_activity BioCarta TSTA3 SARDH MTHFD2 ALOX 15B PHYH MTRR
GPX5 GPX2 PGD CYP24A1 COX5A MB RODH-4 ALDH9A1 ALDH2
CDOl PDHX GPX4 CYP4F11 PDIP PAM AKRlDl AKRlAl P4HB ALDH5A1
TXN CYP26A1 ALDH1A2 ADH5 DDO TXNL GPX3 MEl NCFl
QDPR PHGDH ALDHlAl IDH3B WWOX TXNDC5NNT DEGS PLOD SRD5A2
COXI l ME2 NCF2 DAO RODH CYPI lAl LOXL2 QSCN6 CYP39A1
KMO NCF4 CYP 19Al DHCR7 HM0X2 AKRlBlO FTHFD ME3 ERP70 P5
UQCR LOC51061 ALOX12B COX 15 N0X4 GRHPR ETFB KIAAl 833
UGDH CYPlBl EPX CYCl ADH6 A0C3 CYCS LOXLl GLDC LALPl A0C2
ADH7 SDHD RRM2B INDO DHRS4 BLVRA ADHlA DHRS3 SRD5A1 SPR AKR7A2 TXNL2 AKR7A3 HSD17B8 TXNDC2CYP1A2 HPGD P4HA2 MAOB PDIR ALDH4A1
GRP58 HNRPM HAAO GSR AKR1C4 ZFP90 SDHA ADHlB AKRlCl PRDX2 TXN2
FLJ20793 ASPH AKR1C3 PRDX5 NQO2 ALDH3A1 AKR1C2 AKRlBl ADHlC
H6PD DHDH DHRS2 PPOX TXNDC3 eosinophilsPathway Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. HLA-DRA CCLI l IL5 CCR3 IL3
HLA-DRBl CCL5 CSF2 ephA4Pathway Eph kinases are receptor tyrosine kinases that bind surface-expressed ephrin ligands and are active in neuronal development and platelet aggregation. ITGBl SELP EPHA4 LlCAM RAPlB LYN ITGAl ACTAl FYN EPHBl eponfkbPathway The cytokine erythropoietin (Epo) prevents stress-induced neuronal apoptosis by stimulating anti- apoptotic pathways through JAK2 kinase and NF-kB. EPOR HIFlA NFKBIA JAK2 NFKBl EPO
SOD2 CDKNlA RELA GRINl ARNT epoPathway Erythropoietin, which activates the MAPK pathway, stimulates erythrocyte production and is an effective treatment for anemia. RAFl EPOR STAT5A JAK2 SOSl GRB2 STAT5B HRAS
JUN MAPK3 PTPN6 CSNK2A1 PLCGl EPO FOS MAP2K1 SHC1 ELKl
MAPK8 erbb3Pathway Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. UBE2D1 EGFR ERBB3 EGF NRGl erbb4Pathway ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. PSENl ERBB4 NRG2 PRKCA PRKCBl NRG3 ADAM17 erk5Pathway Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. MEF2B NTRKl MEF2C GRB2
HRAS MAPK7 MAPK3 AKTl MEF2D PIK3CA PIK3R1 PLCGl CREBl MEF2A MAPKl RPS6KA1 SHCl erkPathway Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway.
IGFlR EGFR GNGTl SOSl PDGFRAMAPK3 ITGBl NGFR PTPRR MAP2K1 SHC1
STAT3 MYC RAFl NGFB MKNKl KLK2 GRB2 HRAS MKNK2 DPM2 MAP2K2
RPS6KA5 GNAS MAPKl RPS6KA1 PPP2CA SRC GNBl ELKl erythPathway Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CSF3 KITLG IL9 TGFB2 ILIA IL3 TGFB3 CSF2 IGFl ILI l EPO
IL6 TGFBl CCL3 FLT3 etcPathway Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. GPD2 MTCOl ATP5A1 SDHD SDHC NDUFA I UQCRC I SDHA CYCS SDHB etsPathway The Ets transcription factors are activated by Ras and promote macrophage differentiation.
E2F1 DDX20 HRAS SIN3B RBL2 JUN HDAC5 HDAC2 E2F4 RBLl CSFl
FOS NCOR2 ETS2 SIN3A CSFlR ETV3 ETSl extrinsicPathway The extrinsic prothrombin activation pathway requires the release of thromboplastin from damaged tissues to activate the blood clotting cascade. FGG SERPINCl F5 F2R FGA F2 F7
F3 TFPI PROC FlO PROSl FGB fasPathway Binding of the Fas ligand to the Fas receptor induces caspase activation and consequent apoptosis in the Fas-expressing cell. LMNB2 MAP3K7 ARHGDIB CASP6 JUN RIPK2 PTPN13 CASP7
CASP3 ADPRT PAKl CFLAR CASP8 CASPlO LMNA PRKDC MAP2K4FAF1 MAP3K1 SPTANl FADD LMNBl DFFB RBl TNFRSF6 PAK2 DAXX TNFSF6 DFFA
MAPK8 Fatty_Acid_Degradation BioCarta ACADL GPD2 HADHB FACL4 HADHA CPTlA ACADVL
CPT2 ACADS ACADSB HADHSC FACL6 FACL2 ACAA2 GK ACADM
TPIl SLC25A20 CPTlB GRCC9 GK2 FACL3 CRAT FACL5 LPL fatty_acid_metabolism BioCarta FAAH PPARA CYP4A11 CD36 OKL38 LIPE PCCA
FABPl ALOX12 ALOX15B DHRS3 ABCD2 SC4MOLFABP7 ACOX3 PECI ACADSB
FABP2 FACL2 FASN CYP2J2 PECR ASAHl CROT LPL GNPAT Fatty_Acid_Synthesis BioCarta ACACB ACAA2 PRKAG3FASN ACACA PRKAG2PRKAA2ACLY
SLC25A1 PC PRKABl SCD PRKAGl PRKAAl PRKAB2 HADHSC fbw7Pathway Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNEl E2F1 SKPlA TFDPl CULl CDK2
RBl CDC34 FBXW7 fcerl Pathway In mast cells, Fc epsilon receptor 1 activates BTK, PKC, and the MAP kinase pathway to promote degranulation and arachnidonic acid release. VAVl SOSl PRKCBl PPP3CC MAPK3 JUN CALMl NFATC3 PIK3R1 PLCGl SYTl CALM2 MAP2K1 NFATC2 SHC1 MAP2K7PPP3CA RAFl
CALM3 PPP3CB MAP2K4NFATC1 FCERlA MAP3K1 HRAS LYN GRB2 PLA2G4A
BTK PIK3CA NF ATC4 MAPKl PAK2 FOS SYK ELKl MAPK8 FCERlG feederPathway Sugars such as mannose, galactose, and fructose are enzymatically converted to glucose via "feeder" pathways that lead to glycolysis. TREH PYGM HKl PGMl MPI LCT TPIl KHK PYGL fibrinolysisPathwayThrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to -7O . capture platelets and other blood cells into a clot. FGG F13A1 PLG SERPINB2 PLAU FGA
F2R CPB2 PLAT SERPINEl F2 FGB flumazenilPathway Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA5GPX1 GABRA2SOD1 GABRA3GABRA4GABRA IPRKCE GABRA6 finlppathway The fMLP receptor is a G-protein coupled receptor in neutrophiles that recognizes formylated bacterial peptides and activates NADPH oxidase. GNA15 GNGTl NFKBIA MAPK14PPP3CC RACl MAP2K6
RELA MAPK3 CALMl NFATC3 PAKl SYTl CALM2 MAP2K1 NFATC2 PPP3CA CALM3 PIK3C2G RAFl PPP3CB CAMKl NFATCl MAP3K1 HRAS NCFl MAP2K3 PLCBl
NFATC4 MAP2K2NFKB1 MAPKl GNBl FPRl ELKl NCF2 CAMKlG fosbPathway BLACK PPPlRlB GRIA2 JUND FOSB CDK5 freePathway Neutrophils release superoxide to induce lysis in invading bacteria; in neighboring endothelial cells, superoxide dismutase scavenges radicals but produces pro-apoptotic peroxides. XDH GPXl NOXl TNF
SODl NFKBl GSS IL8 GSR RELA fxrPathway The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. NR1H4 RXRA FABP6 NR0B2 NR1H3 LDLR
G13_Signaling_Pathway BioCarta PIK3R2 WASL ARHGDIB CIT RACl PRKCLl RHPN2
ARHGDIG DIAPHl PAK3 CALMl LIMKl RTKN MYBPH PIK3CD PIK3CB IQGAP2
CALM2 PFNl PLA2G12 IQGAPl CALM3 CDC42 CFL2 PPPlCB CFLl WAS
ARHGEFl GNA13 MAP3K4PIK3CA PIP5K2AMAPK1 OARHA gl Pathway BioCarta ATM TGFB2 CDK6 MADH4 TFDPl MADH3 CCNAl CCNDl HDACl
SKP2 ABLl GSK3B CDKNlB E2F1 CDC25A CDK2 TGFB3 ATR CCNEl
CDC2 TP53 DHFR CDKN2A CDK4 RBl CDKNlA TGFBl CDKN2B glpPathway BLACK GALKl GALE GALT g2Pathway BioCarta ATM PRKDC EP300 CDC25A CDC25B ATR YWHAQ CDC2 CDC25C
MDM2 GADD45A WEEl TP53 CDKN2D CHEK2 YWHAH CCNBl RPS6KA1
PLK CDC34 CDKNlA CHEKl BRCAl MYTl gabaPathway BioCarta GABRA5NSF GABRA2DNM1 GPHN GABRA3SRC GABRA4GABRA1
GABARAP GABRA6UBQLN: 1 gata3 Pathway BioCarta ILl 3 GATA3 NFATCl PRKAR2A PRKACE ! JUNB IL5
MAPK14MAP2K3PRKAR2B IL4 PRKARlA MAF PRKACG PRKARlB
NFATC2 gcrPathway BioCarta CALM3 ADRB2 GNGTl NR3C1 CRN HSPCA RELA AKTl CALMl
NOS3 PIK3CA PIK3R1 NFKBl ANXAl GNAS SYTl CALM2 GNBl NPPA ghPathway BioCarta STAT5A GHR JAK2 SOSl SLC2A4 PRKCBl GHl MAPK3 INS
PIK3R1 PLCGl INSR MAP2K1 SHCl IRSl SOCSl RAFl SRF PRKCA TCFl
GRB2 STAT5B HRAS PIK3CA PTPN6 MAPKl RPS6KA1 gleevecPathway BioCarta RAFl MAP2K4STAT5A MAP3K1 BCL2 JAK2 SOSl GRB2 STAT5B
HRAS CRKL JUN MAPK3 AKTl STATl PIK3CA PIK3R1 FOS MAP2K1 MAPK8
BCR MYC
Glycogen Metabolism BioCarta PYGM PHKB PPP2R2C PPP2R1B PPP2CB PPP2R5A
CALMl GSK3A CALM2 AGL CALM3 PPP2R5C GSK3B UGP2 PPP2R3A
PYGB GYG2 PPP2R2A PHKG2 PR48 PPP2R5D PYGL GYS2 PPP2R2B
PPP2R1A PHKGl PGMl GYG PHKAl PPP2R5E GYSl GBEl PPP2CA
PPP2R4 PPP2R5E ! PHKA2 glycolysisPathway BioCarta GAPD HKl PKLR GPI ALDOB PGKl PFKL PGAMl TPIl
ENOl gpcrPathway BioCarta PRKAR2A GNGTl PRKCBl PPP3CC RPS6KA3 PRKAR2B
JUN MAPK3 PRKARlA CALMl ADCYl PRKACG NFATC3 PLCGl SYTl
CALM2 MAP2K1 NFATC2 PPP3CA CALM3 RAFl PPP3CB GNAQ GNAIl NFATCl PRKACB
HRAS PRKCA PRKARlB NFATC4 GNAS CREBl FOS GNBl ELKl
GPCRs Class A Rhodopsin-like GO AVPRlB GALRl AVPR2 DRD4 GPRl 7 ADRA2C0XTR
CCR3 NPY5R GPR50 HTR2C CCR8 GPR66 TSHR GPRl 05 DRD3 OPN3 GALR3
LHCGR PPYRl NMBR MClR CCR9 GALR2 AVPRl AMASl ET(B)R-LP-2 BDKRBl
FPRLl CHRMl HTR2B GPR87 ADRA1BCHRM2 EDNRA CMKLRl [ CCR7 OPRKl
CNRl GPR86 P2RY12 OR7C1 CCR5 CHRM4 GPR91 CHRM5 CCBP2 GPR63 GRPR
ADORA2 S IL8RB GPR35 F2R VIPRl FKSG79 CNR2 FPRL2 GPR24 P2RY5
PTGER3 HTRlD CXCR3 AGTRl P2RY2 GPR23 NTSR2 GPR92 ADRAlE ) HTR2A
GPR37 ADRAlA ADRB2 FSHR PTGIR F2RL2 CXCR4 EDNRB CCR4 LTB4R
CCKAR GHSR P2RY6 OPRLl ADRA2A ADORAl NPYlR GPR85 HTR7
F2RL1 OPRDl AGTRLl HTR4 MTNRl^ NTSRl PTGER2 HCRTR2 CCR2 IL8RA
PTGER4 ADRB3 MTNRlE 5 AGTR2 HRHl HTRlF PTGERl NPY2R CCRLl RRH
HTRlE GPRlO SREB3 CCRL2 CMKOR: 1 HRH3 GPR27 CX3CR1 AD0RA2A
BCL9L BDKRB2OT7T022GPR74 GPR30 BLRl FPRl C3AR1 OPRMl C5R1 NPY6R
HTRlA DRDl TBXA2RHTR1B ORlFl GPR4 P2RY1 PTGFR ADRBl DRD2 GPR44
NMU2R CCKBR PTGDR TRHR HCRTRl FBXW2 HTR5A RGR GPR2 CCRl PTAFR
AD0RA2B GPCRs_Class_A_Rhodopsin-like_2 GO GPRl 8 GPR68 HM74 MGC29643 CYSLTR2 CYSLTRl GPR161 GPR34 GPR45 GPR39 GPR75 P2RX4 H963
GPCRs_Class_B_Secretin-like GO CALCRLSCTR GIPR GLPlR ELTDl LPHNl CALCR
GLP2R GCGR VIPRl ADCYAPlRl GPR64 EMRl CMKORl PTHRl GHRHR VIPR2 CD97 EMR2 PTHR2 LPHN3 CRHRl LPHN2 CRHR2 GPCRs_Class_C_Metabotropic_glutamate_pheromone GO GABBRl GRMl GPRC5B GRM5 CASR
RAD GRM3 GPRC5C GPR51 GRM7 GPRC5D GRM8 GRM4 GRM2 gsk3Pathway BioCarta WNTl PRKR RELA AKTl LBP CD14 IRAKI CCNDl PIK3R1 MYD88 APC CTNNBl TOLLIP GNAIl GSK3B PDPKl LEFl TLR4 LY96 AXINl
GJAl FZDl PIK3CA NFKBl DVLl PPP2CA TIRAP gsPathway BioCarta ADCYl GNGTl GNAS PRKACA GNBl PRKARlA hbxPathway BioCarta HBXIP PTK2B SOSl HRAS GRB2 CREBl SRC SHCl hcmvPathway BioCarta MAP3K1 SPl MAPK14MAP2K3MAP2K6MAPK3 RELA AKTl PIK3CA
PIK3R1 MAP2K2NFKB1 RBl CREBl MAPKl MAP2K1 hdacPathway BioCarta IGFlR CABINl MAPK14PPP3CC MAP2K6AKT1 MEF2D CALMl INS
PIK3R1 AVP INSR Y YWWHHAAHH SSYYTTll CALM2 NFATC2 PPP3CA MYODl CALM3 PPP3CB
MEF2B CAMKl NFATCl M MEEFF22CC MMAAPPKK77 HDAC5 IGFl PPIIKK33CCAA MMEEFF22AA CCAAMMKKllG hifPathway BioCarta EP300 CCOOPPSS55 HHSSPPCCAA JUN ARNT VVEEGGFF AASSPPHH HHIIFFllAA VHL
NOS3 EDNl EPO CCRREEBBll PP44HHBB LDHA hivnefPathway BioCarta PSENl PPSSEENN22 RREELLAA CASP6 CCRRAADDDD CCAASSPP33 CCAASSPP77 AADDPPRRTT BAG4
BIRC2 CFLAR MAP2K7PPRRKKDDCC TTNNFF TRAF2 BBIIRRCC33 MMAAPP33KK11 BBCCLL22 PPTTKK22 CHUK
SPTANl NUMAl MAP3K14 4 LLMMNNBBll CYCS MDM2 MMAAPP33KK55TTNNFFRRSSFF66 DAXX
MAPK8 BID CASP9 LLMMNNBB22 NFKBIA TNFRSFlA AARRHHGGDDIIBB GGSSNN TNFRSFlB
BIRC4 RIPKl CASP8 LMNA RASAl TRADD ACTGl FADD CCDDCC22LL22 CCDDCC22LL1 PRKCD
DFFB TRAFl NFKBl RBl PAK2 CASP2 TNFSF6 DFFA AAPPAAFFll hsp27Pathway BioCarta CASP9 TNF BCL2 HSPB2 HSPBl ILIA ACTAl CYCS
MAPKAPK3 CASP3 MAPKAPK2 TNFRSF6 DAXX APAFl FAS FASLG huntingtonPathway BLACK HD HDACl CREBl CREBBF ifhaPathway BioCarta STATl ISGF3G IFNAR2 STAT2 TYK2 IFNBl IFNARl IFNAl JAKl ifhgPathway BLACK STATl IFNG JAK2 IFNGR2 IFNGRl JAKl igflmtorPathway BioCarta EIF2S1 IGFlR GSK3B PDPKl INPPLl PDK2 EIF2S2 AKTl FRAPl
EIF4E IGFl RPS6 PIK3CA PIK3R1 EIF4EBP1 EIF2S3 PPP2CA EIF2B5 RPS6KB1
PTEN igfl Pathway BioCarta RAFl IGFlR RASAl PTPNI l SRF SOSl GRB2 HRAS JUN
MAPK3 IGFl PIK3CA PIK3R1 CSNK2A1 FOS MAP2K1 SHCl IRSl ELKl
MAPK8 igflrPathway BioCarta RAFl IGFlR SOSl GRB2 HRAS MAPK3 AKTl PIK3CA PIK3R1
BAD YWHAH MAPKl MAP2K1 SHCl IRSl illOPathway BioCarta TNF STAT5A BLVRA ILlORA ILIA ILlORB HMOXl JAKl STATl
IL6 BLVRB ILlO STAT3
I112Pathway BioCarta CD3E TRB@ ILl 2B CD3Z STAT4 IFNG JAK2 IL12RB1 IL12RB2
MAPK14TRA® IL12A TYK2 MAP2K6JUN ILl 8 CXCR3 CD3G ETV5 CCR5
CD3D MAPK8 ILl 8Rl ill7Pathway BioCarta TRB@ CD3E CSF3 CD3Z KITLG CD2 IL8 TRA@ CD4
CD58 IL3 CD34 IL17 CD3G CD8A CD3D IL6 ill8Pathway BioCarta ILl 8 IL2 ILl 2B CASPl IFNG IL12A illrPathway BioCarta TGFB2 NFKBIA MAP3K7IRAK2 MAPK14MAP2K6IL1A RELA JUN
IRAKI MAP3K7IP1 IKBKB MYD88 TRAF6 ILlRAP TOLLIP TNF SITPEC MAP3K1
CHUK ILlB MAP2K3IFNB1 MAP3K14 TGFB3 ILlRN NFKBl IL6 ILlRl
IRAK3 IFNAl MAPK8 TGFBl il22bpPathway BioCarta IL22RA2 STAT5A JAK2 ILlORA STAT5B TYK2 SOCS3 JAKl STATl
JAK3 IL22 IL22RA1 STAT3 il2Pathway BioCarta RAFl IL2 STAT5A IL2RB SOSl GRB2 STAT5B HRAS LCK
JUN MAPK3 IL2RG JAKl JAK3 CSNK2A1 FOS MAP2K1 SHCl SYK
ELKl MAPK8 IL2RA il2rbPathway BioCarta STAT5A SOSl MAPK3 IL2RG AKTl ZNFNl A3 S0CS3 PIK3R1
CFLAR NMI PPIA SHCl IRSl SOCSl IL2RA RPS6KB1 MYC RAFl
IL2RB E2F1 BCL2 CBL STAT5B HRAS GRB2 CRKL JAKl JAK3 PIK3CA
PTPN6 BAD TNFRSF6 MAPKl FOS SYK TNFSF6 BCL2L1 iBPathway BioCarta RAFl CSF2RB STAT5A JAK2 SOSl GRB2 HRAS STAT5B IL3
MAPK3 IL3RA PTPN6 FOS MAP2K1 SHCl il4Pathway BioCarta JAK3 GRB2 STAT6 IL4 SHCl IL2RG IRSl AKTl IL4R
RPS6KB1 JAKl il5Pathway BioCarta HLA-DRA CCLI l IL5 ILlB CCR3 CD4 IL4 IL5RA
IL6 HLA-DRBl ilόPathway BioCarta RAFl CEBPB PTPNH SRF JAK2 SOSl GRB2 HRAS JUN MAPK3 JAKl IL6ST IL6R JAK3 CSNK2A1 FOS MAP2K1 SHCl IL6
STAT3 ELKl il7Pathway BioCarta EP300 STAT5A BCL2 STAT5B LCK IL2RG JAKl JAK3 PIK3CA
PIK3R1 IL7R PTK2B IL7 NMI FYN CREBBP
Inflammatory Response Pathway BioCarta IL2 COLlAl ZAP70 LAMBl LCK THBS3 LAMC2
IL4 IL2RG FNl LAMCl CD86 IL5RA IL4R IL2RA LAMA5 VTN IL2RB
IFNG IL5 COL1A2 MUCl LAMB2 COL3A1 TNFSF5 CD80 CD28 inflamPathway BioCarta IL13 IL2 TGFB2 IL4 ILIA ILl 5 CSF2 PDGFA CSFl
HLA-DRBl TNF HLA-DRA ILl 2B CSF3 IFNG IL5 IL8 IL12A
CD4 IFNBl IL3 TGFB3 ILI l IL7 IL6 IFNAl ILlO TGFBl LTA insulin signalling BioCarta LNPEP CSN2 DOKl SLC2A4 LEP PIK3R1 EIF4EBP1 HK2
PCK2 PRKCZ IRSl RPS6KB1 SERPINB6 ARAFl GSK3B AKT2 PDPKl
IGFBPl MKNKl GRB2 HRAS TIEG PIK3CA PKLR PTPRF UCP2 MAP2K2PIK3R3
BCL2L1 ACACB PRKCBl AEBPl CRK GABl AKTl FRAPl SOS2 INS AKT3
INSR GSK3A PIK3CB MAP2K1 PPIA UCPl RAFl GCK CBL RETN PRKCG
CAPl SLC2A1 G6PD G6PC GCG SLC27A4 PRKCI NOS2A PPARG ACOXl
ADRB3 DUSP14 SERPINEl SHC3 SREBFl SORBSl VEGF RRAS RPS6KA1
FBPl PIK3R2 EIF2B1 PTPNI l RRAS2 SOSl ACACA JUN RPL13A EIF4E NPY
BRD4 PTPNl NCKl DF CEBPA SHCl PRL CEBPB KRAS2 ERCCl PKM2 TG
BRAF IRS4 GAPD PPPlCA IRS2 ORMl MAPKl FOS NCK2 ACTB LDLR insulinPathway BioCarta RAFl RASAl PTPNI l SRF SLC2A4 SOSl GRB2 HRAS JUN
MAPK3 INS PIK3CA PIK3R1 CSNK2A1 INSR FOS MAP2K1 SHC1 IRSl
ELKl MAPK8 integrinPathway BioCarta SOSl BCARl PXN MAPK3 JUN CSK ACTNl ITGBl CAPNl
MAP2K1 SHCl BCR RAFl RAPlA ACTN3 PTK2 ACTN2 GRB2 HRAS CRKL
PPP1R12B VCL ACTAl ZYX TNS ROCKl CAVl CAPNSl MAP2K2TLN1
MAPKl SRC ITGAl FYN GRF2 CAPNS2 MAPK8 ARHA intrinsicPathway BioCarta FGG SERPINCl F5 COL4A1 COL4A5 F8 F2R FGA
COL4A4 FI l KLKBl F2 COL4A3 PROC KNG COL4A6 FlO SERPINGl
COL4A2 PROSl F9 F12 FGB ionPathway BioCarta P2RY2 PLCGl PTK2B PRKCA PRKCBl keratinocytePathway BioCarta EGFR NFKBIA SPl PRKCBl TNFRSFlA MAPK14MAP2K6
RELA JUN MAPK3 TNFRSFlB PRKCH IKBKB RIPKl CEBPA MAP2K1 PRKCE
ETS2 MAP2K7PRKCQ ETSl RAFl MAPKl 3 TNF MAP2K4TRAF2 MAP3K1 BCL2
CHUK EGF PRKCA HRAS MAP2K3 PRKCG MAP3K14 H0XA7 MAP3K5 PRKCD
NFKBl TNFRSF6 MAPKl PPP2CA DAXX FOS TNFSF6 MAPK8 ketonebodiesPathway BLACK HMGCSi > ACATl HMGCL BDH krebPathway BioCarta ACO2 SUCLA2 MDHl FH CS IDH2 SDHA OGDH
Krebs-TCA Cycle BioCarta PDK4 MDHl DLAT PDK2 IDH2 PDHAl KIAA 1348 PDHB
SDHB PPM2C IDH3A FH PDK3 DLST DLD ACO2 PDKl PDHA2 MDH2
SUCLGl PDHX CS SDHA IDH3B OGDH PC SDHD SDHC IDH3G lairPathway BioCarta TNF SELP C5 IL8 C3 ILIA SELPLG ITGA4 ITGBl
VCAMl C7 ICAMl BDK ITGB2 ITGAL IL6 C6 ldlPathway BioCarta CCL2 CSFl ACATl LPL IL6 LDLR lechtinPathway BioCarta MBL2 C2 MASP2 C5 C7 C8A C3 C4B MASPl
C4A C9 C6 leptinPathway BioCarta LEPR PRKABl CPTlA LEP PRKAGl PRKAAl ACACA PRKAB2 PRKAA2
PRKAG2 longevityPathway BioCarta IGFlR SOD3 CAT GHR HRAS SOD2 GHl AKTl IGFl
SODl PIK3CA PIK3R1 SHCl FOXO3A lymphocytePathway BioCarta ITGBl ITGA4 SELL ICAMl CD44 ITGAL ITGB2 PECAMl
SELE malatePathway BLACK MDHl GOTl SLC25A11 SLCl A3 malatexPathway BioCarta SLC25A1 ACLY MDHl PC MEl CS SLC25A11
PDHAl
MAP kinase activity GenMAPP MAPK13 MAPK4 MAPK12MAPK1 MAPK14MAPK7 MAPK3
MAPKI l
MAP kinase kinase activity GenMAPP MAPK10MAP2K3MAPK14MAP2K1 MAP2K6MAP2K'
MAPKAPK5 MAPKAPK3
MAPOOOlO Glycolysis Gluconeogenesis GenMAPP PFKM DLAT PGKl PFKL PDHAl
ALDH3A2 PDHB ENOl PRO1073 EN02 HK2 ALDHlBl DLD
LDHA BPGM HKl PDHA2 ALDH2 PFKP ADH6 LDHC ALDH3B2 PKLR
HK3 GRCC9 ADH7 ACYPl ALDOC BID FBPl FBP2 ADHlA ALDOB PGAMl
ALDOA LDHB ENO3 ADH5 ALDH3B1 ALDH1A3 ADH4 GCK PKM2
TPIl FMNL3 ADHlB ACYP2 ALDHlAl GAPD ALDH3A1 PGMl GPI
ADHlC G6PC PGAM2 MAP00020_Citrate_cycle_TCA_cycle GenMAPP ACO2 MDHl MDH2 CS AACCOOll IDH2
SDHA SDHB OGDH ACLY IDHl PC IDH3A PCKl FH DDLLSSTT IDH3G
DLD MAP00030_Pentose_phosphate_pathway GenMAPP P PFKM FBP2 RBSK AALLDDCOB PFKP
PFKL TALDOl PRPSl FMNL3 ALDOA GG66PPDD PRO1073 PGMl GGPPII PRPS2
H6PD ALDOC PGD FBPl MAP0005 l_Fructose_and_mannose_metabolism GenMAPP P PFKM FBP2 ALDOB PFKL KHK
ALDOA GMPPB PFKFBl SORD PMMl HK2 FPGT HKl GCK MPI PFKP
TPIl FMNL3 PMM2 HK3 GRCC9 AKRlBl ALDOC GMPPA FBPl MAP00052_Galactose_metabolism GenMAPP PFKM GALKl GALE GLBl GCK HKl
UGP2 MGAM PFKP GALK2 PFKL FMNL3 B4GALT2 GALT HK3 PGMl
AKRlBl B4GALT1 G6PC HK2 LCT GAA LALBA GLA
MAP00062_Fatty_acid_biosynthesis_path_2 GenMAPP ACAA2 HADHB EHHADH ACATl
ECHSl ACAAl HADHA MAP00071_Fatty_acid_metabolism GenMAPP CYP4A11 CYP2B6 ALDH3A2 FACL4
HADHA CYP2E1 CYP2C18 CYP19A1 ACOXl CPTlA CPT2 ALDHlBl
ACADS FACL2 ALDH2 ACADM ADH6 CYP2J2 CYP3A5 CYP51A1 ADH7 FACL5
CYP2D6 CYP4B1 ACADL ADHlA HADHB CDK3 GCDH CYP3A4 EHHADH ACATl CYP1A2 ADH5 CYPlAl ADH4 ACAA2 CYP4F8 ECHSl ADHlB ALDHlAl CYP2C8 ADHlC CYP2F1 CYP2A7 FACL3 CYP2A6 ACAAl CYP2C9 CYP3A7
MAPOO 100_Sterol_biosynthesis GenMAPP MVK NQO2 SC5DL IDIl LSS HMGCR
FDFTl FDPS SQLE MVD
MAPOO 120_Bile_acid_biosynthesis GenMAPP ADH4 ACAA2 ADHlA HADHB ALDH2 CYP7A1 CYP27A1 BAAT ADHlB ALDH3A2 ADH6 ALDHlAl SRD5A1 SOATl
AKRlDl ADH7 CEL LIPA ADHlC ADH5 SRD5A2 ALDHlBl ACAAl
MAPOO 140 C21 Steroid hormone metabolism GenMAPP HSD3B1 CYPI lAl CYP11B2
HSD3B2 HSDI lBl CYP21A2 CYP17A1 HSDl 1B2 CYPI lBl AKRlDl
MAPOO 150_Androgen_and_estrogen_metabolism GenMAPP STS HSD3B1 CYP11B2
ARSE HSD3B2 STE ADH6 UGT2B15 SRD5A1 AKRlDl CYPI lBl HSD17B2
ARSD UGT2B4 HSDl IBl SRD5A2 HSD17B3 HSDl 1B2
MAPOO 190_Oxidative_phosphorylation GenMAPP ATP6V1B2 ATP6V0A1 ATP6V1G2
UQCRFSl ATP4B ZNF183 NDUFSl ATP4A ATP7A ATP6V0A4 COX6C SDHB
ATP6V0B ATP6V0E UQCRC2COX4I1 COX7C COX6A1 ATP7B ATP6V1A
COX5A ATP12A UQCRB COX6A2ATP6V1F ATP6V1G1 COX7A2NFKBIL2
ATP6V1B1 COX5B SDHA COX7A1 MPP5 ATP6AP1 ATP6V0D1 COX7B
NDUFA5NDUFV2ATP6V1D COX6B ATP6V0C UQCRC1ATP5E ATP6V1E1
ATP6V1C1 ATP6V1G3
MAPOO 193_ATP_synthesis GenMAPP ATP6V1G1 ATP6V0A1 ATP6V1B2 ATP6V1G2
ATP6V1B1 MPP5 ATP6V0A4 ATP6AP1 ATP6V0D1 ATP6V0B
ATP6V0E ATP6V1D ATP6V0C ATP6V1E1 ATP5E ATP6V1C1
ATP6V1A ATP6V1F ATP6V1G3
MAPOO 195_Photosynthesis GenMAPP ATP6V1G1 ATP6V0A1 ATP6V1B2 ATP6V1G2
ATP6V1B1 MPP5 ATP6V0A4 ATP6AP1 ATP6V0D1 ATP6V0B
FDXR ATP6V0E ATP6V1D ATP6V0C ATP6V1E1 ATP5E ATP6V1C1
ATP6V1A ATP6V1F ATP6V1G3
MAP00220_Urea_cycle_and_metabolism_of_amino_groups GenMAPP ASL PYCS CPSl
ACYl OTC ASS CKM OAT ARG2 PYCRl GAMT CKMT2 SMS GLUDl ARGl VTIlB ODCl CKMTl CKB MAP00230_Purine_metabolism GenMAPP ADSS POLE POLR2E GMPS ADCY7 POLR2J2
ECGFl NPR2 NMEl PDElA ATP5J ADCY6 ADA PDE4A POLB GDA NT5C1B NP
GUCY2D POLD2 POLRlB IMPDHl IGFBP7 ADCY9 DGUOK APRT POLDl XDH
PFAS AMPD2 GUCY2F HPRTl PDE4B POLR2D RRM1 NPRl POLA POLR2I ADK
PKLR RRM2 DCK PRPS2 POLR2F PPAT GUCY 1A2 POLR2K PDE6G POLR2G
AMPDl POLG POLR2L POLR2H ADSL PDE6C ATIC GUCY2C AMPD3 PDE5A
NME2 POLR2C ADCYl POLR2B PDE4C P0LR2J GUCY1A3 PKM2 PDE4D PRPSl POLR2A PDE6B PAICS POLRMT ADCY3 AKl ADCY2 GMPR GUCY1B3 AK2 FHIT GART D0K4 IMPDH2 ADCY8
MAP00240_Pyrimidine_metabolism GenMAPP POLE POLR2E UMPK POLR2L POLR2J2DUT
POLR2H ECGFl NMEl UMPS POLB NT5C1B NME2 POLR2C NP POLD2 POLRlB IGFBP7 CTPS POLR2B TYMS CAD UBTF POLDl POLR2J DHODH POLR2D RRM1 POLR2A AK3 POLA POLR2I POLRMT DCTD RRM2 DCK POLR2F DPYD
CDA TKl POLR2K DPYS POLR2G POLG DOK4
MAP00251_Glutamate_metabolism GenMAPP ALDH5A1 GMPS GAD2 GCLC GOTl
GA GSS CPSl GSR QARS GADl ABAT GOT2 GFPTl GPT EPRS PPAT GLUDl GLUL CAD GCLM MAP00252_Alanine_and_aspartate_metabolism GenMAPP ? ADSS DARS ASL AGXT GAD2
GOTl ADSL ASPA AARS GADl ASS ABAT GOT2 NARS GPT DDX3X PC
CRAT DDO ASNS CAD MAP00260_Glycine_serine_and_threonine_metabolism GenMAPP SHMTl AGXT PISD ALASl
GARS SHMT2 LOC56901 AOC3 GLDC CBS AMT AOC2 GAMT SDS
KIAA0335 MAOA HBG2 SARS ABPl TARS MAOB BHMT DAO DLD
MAP00271_Methionine_metabolism GenMAPP CBS MATlA CTH DNMTl AHCY MTR
MARS BHMT MAP00272_Cysteine_metabolism GenMAPP CARS CTH GOTl SDS LDHB MPST
LDHC GOT2 LDHA MAP00280_ValineJeucine_and_isoleucine_degradation GenMAPP HADHB PCCA MCCCl ALDH3A2
PCCB HADHA BCKDHB EHHADH AOXl ALDHlBl HMGCSl
ACADS C14orf45 HMGCS2 ACAA2 BCKDHA ALDH2 MCCC2 ALDH6A1
ACADM ECHSl IVD HMGCL ALDHlAl MUT OXCT ACAAl M AP00310_Lysine_degradation GenMAPP SHMTl ALDH2 SSHHMMTT22 EECCHHSSll AAAASSSS LOC56901
ALDH3A2 ALDHlAl HADHA BBOXl OGDH GGCCDDHH EEHHHHAADDHl i ACATl
PLOD ALDHlBl DLST
MAP00330_Arginine_and_proline_metabolism GenMAPP ASL NOS2A ALDH3A2 ASS
AMDl G0T2 OAT ARG2 NNOOSS3: 5 EEPPRRSS RARS GLUDl ALDHlBl VTIlB
MAOB CKMTl SAT GOTl AALLDDH] H22 CCPPSSll OTC ALDHlAl AOC3 CKM
AOC2 PYCRl GAMT CKMT2 SSMMSS MMAAOOAA ARGl ABPl AGMAT P4HA1 NOSl
OODDCCll PP44HHBB CCKKBB DAO MAP0034 iO0_ HHiissttiicd liinnee_ mmeettaalb )oolliissmm GenMAPP ALDH2 HARSL ASPA HDC ALDH3A2 A AOOCC33 AALLDDHHUlA illl DDC ALDH3B2 A0C2 HAL ALDH3A1 MAOA A ALLDDHHUlB 31l AABBPPll ALDH3B1 HNMT ALDHl A3 MAOB HARS
MAP0035 iO0_ TTwyrooss iinnee_ mmeettaabb oolliissmm GenMAPP TAT COMT DBH ADHlA HPD ARVCF DDC GOT2 HGD AOXl ADH5 ALDH3B1 ALDH1A3 MAOB TH FAH PNMT ADH4 GOTl ADHlB ADH6 A0C3 ALDH3A1 AOC2 ALDH3B2 ADH7 MAOA ADHlC ABPl TYR MAP00360_Phenylalanine_metabolism GenMAPP TAT HPD GOTl LPO A0C3
DDC GOT2 ALDH3B2 AOC2 ALDH3A1 MAOA MPO ABPl ALDH3B1 ALDH1A3 MAOB
MAP00361_gamma_Hexachlorocyclohexane_degradation GenMAPP CYP2B6 ALPL CYP2E1 CYP2C18
CYP3A4 CYP19A1 ACP5 CYP1A2 ACPP CYPlAl CYP4F8 ACP2 CYP2J2 CYP3A5
ALPP PONl CYP51A1 ACPI ALPPL2 CYP2C8 CYP2A7 CYP2F1 CYP2A6 CYP2D6
ACPT ALPI CYP4B1 CYP3A7 CYP2C9
MAP00380_Tryptophan_metabolism GenMAPP ACMSD CYP2B6 ALDH3A2 CYP2E1 DDC
HADHA CYP2C18 CYP3A4 GCDH CYP19A1 EHHADH ACATl CYP 1A2
AOXl ALDHlBl WARS MAOB TDO2 CYPlAl KYNU CAT ALDH2 CYP4F8
AANAT ECHSl HAAO CYP3A5 A0C3 CYP2J2 ALDHlAl OGDH CYP51A1
AOC2 CYP2C8 MAOA CYP2A7 CYP2F1 CYP2A6 ABPl CYP2D6 CYP4B1 WARS2 ASMT
CYP3A7 CYP2C9 INDO MAP00400_Phenylalanine_tyrosine_and_tryptophan_biosynthesis GenMAPP TAT PAH EN02
GOTl ENO3 BID GOT2 ENOl MAP00410 beta Alanine metabolism GenMAPP GAD2 ALDH2 ACADM ECHSl ALDH3A2
GADl AOC3 ALDHlAl HADHA ABAT A0C2 SMS EHHADH DPYD
ALDHlBl ABPl DPYS
MAP00430_Taurine_and_hypotaurine_metabolism GenMAPP GAD2 GADl BAAT GGTl
MAP00450_Selenoamino_acid_metabolism GenMAPP CBS MATlA CTH AHCY MARS
GGTl
MAP00460_Cyanoamino_acid_metabolism GenMAPP SHMTl SHMT2 LOC56901 GGTl
MAP00480_Glutathione_metabolism GenMAPP GSTM2 GPX3 GSTTl MGSTl GCLC GSTPl
GSS GSR IDH2 GPX4 GGTl GPXl GSTMl G6PD IDHl GSTA2 GSTM5
GSTM3 GSTT2 GPX2 GSTM4 GCLM
MAP00500_Starch_and_sucrose_metabolism GenMAPP AGL PYGM GCK HKl MGAM
UGP2 PYGB ADH6 AMYlA UGT2B15 PYGL GYS2 PRO 1073 GUSB
HK3 PGMl GPI G6PC HK2 GYSl UGT2B4 GBEl GAA
MAP00510_N_Glycans_biosynthesis GenMAPP DDOST ALG5 GCSl B4GALT3 MGATl
B4GALT2 MAN2A1 DPAGTl B4GALT5 MGAT2 DPMI SIAT6 SIATl
B4GALT1 FUT8 MGAT3 PPOX FLJ21924
M AP00512_O_Glycans_biosynthesis GenMAPP GALNT2 SIAT4A GALNT8 GALNT7 GALNT9 TUWD 12
GALNTl GCNTl GALNT3 GALNT6 MAP00530_Aminosugars_metabolism GenMAPP GCK HKl HEXA DIAl CMAS PGM3
GNE HEXB GFPTl RENBP PGMl HK3 HK2 NAGLU MAP00531_Glycosaminoglycan_degradation GenMAPP GLBl GALNS GUSB HEXA ARSB
IDS IDUA GNS NAGLU HEXB MAP00532_Chondroitin_Heparan_sulfate_biosynthesis GenMAPP HS3ST3A1 B3GAT3 HS3ST2 HS3ST1 B4GALT7 XYLT2 HS3ST3B1
MAP00533_Keratan_sulfate_biosynthesis GenMAPP B4GALT5 SIAT6 SIATl B4GALT1
B4GALT3 FUT8 B4GALT2 PPOX
MAP00561_Glycerolipid_metabolism GenMAPP DGATl ALDH3A2 SERPINBl PNLIPRPl
CPTlA CPT2 ACHE GPDl PNLIPRP2 ALDHlBl EKIl GLA PLA2G1B ALDH2 PLA2G4A ADH6 PLA2G2A ALPPL2 ADH7 GRCC9 DGKQ PLA2G5
ALPI CHAT PCYTlA GPD2 PNLIP PISD CHK ADHlA ALPL PAFAHlBl DGKG ADH5 DGKA GLBl ADH4 LIPC GK TPIl ADHlB ALDHlAl ALPP AKRlBl CEL ADHlC PAFAH2 AGPS DGKE LPL
MAP00562_Inositol_phosphate_metabolism GenMAPP PIK3C2G PIK4CA PLCB2 INPP4B
PIP5K2B INPPLl PIK3C2A INPP4A PLCDl IMPAl PIK3C2BPIK3CA PLCG2 PLCGl
INPPl ITPKA PIK3CB ALDRL6 ITPKB PIK3CG
MAP00590_Prostaglandin_and_leukotriene_metabolism GenMAPP CBR3 PTGDS PTGS2 PLA2G1B
PGDS LTA4H ALOX12 PLA2G4A PTGIS GGTl ALOX15 PLA2G2A TBXASl
CYP4F3 ALOX5 PLA2G5 PTGSl CBRl CYP4F2
MAP00600_Sphingoglycolipid_metabolism GenMAPP GLBl CST NEUl HEXA UGCG
GBA ARSE HEXB ASAHl ARSA ARSD B3GALT4 GALGT GLA MAP00601_Blood_group_glycolipid_biosynthesis_lact_series GenMAPP FUT2 ABO FUT6
FUTl FUT5 FUT3 MAP00602_Blood_group_glycolipid_biosynthesis_neolact_series GenMAPP FUT2 B4GALT3
FUT6 B4GALT2 FUT5 B4GALT5 B3GNT1 GCNT2 ABO SIATl B4GALT1
FUTl PPOX FUT3 MAP00603_Globoside_metabolism GenMAPP FS SIAT4A FUT2 HEXA FUT6 GLA
FUTl NAGA HEXB FUT5 FUT3 MAP00620_Pyruvate_metabolism GenMAPP ACACB MDHl DLAT GLOl PDHAl ACACA
ALDH3A2 PDHB ME3 LDHB ACATl ADH5 ALDHlBl HAGH GRHPR
LDHA DLD PDHA2 MEl PKM2 MDH2 ALDH2 ACYP2 ALDHlAl LDHC
PKLR AKRlBl PC PCKl ACYPl ME2 MAP00630_Glyoxylate_and_dicarboxylate_metabolism GenMAPP HAO2 ACO2 MDHl MDH2
MTHFD2 HAOl CS ACOl MTHFDl GRHPR
MAP00632_Benzoate_degradation GenMAPP GCDH EHHADH ACATl ACYPl ECHSl
ACYP2 HADHA MAP00640_Propanoate_metabolism GenMAPP C14orf45 ACACB PCCA ALDH2 ALDH6A1
ACADM ECHSl ACACA PCCB ALDH3A2 ALDHlAl MUT LDHC HADHA
ABAT EHHADH ACATl LDHB ALDHlBl LDHA
MAP00650 Butanoate metabolism GenMAPP ALDH5A1 HMGCS2 PDHA2 GAD2
ALDH2 ECHSl PDHAl HMGCL ALDH3A2 GADl ALDHlAl PDHB HADHA BDH ABAT OXCT EHHADH ACATl ALDHlBl HMGCSl ACADS
MAP00670_One_carbon_pool_by_folate GenMAPP SHMTl AMT DHFR FTHFD MTR
SHMT2 ATIC MTHFD2 MTHFDl TYMS LOC56901 GART
MAP00680_Methane_metabolism GenMAPP SHMTl CAT MPO SHMT2 LPO ADH5
LOC56901 M AP00710_Carbon_fixation GenMAPP FBP2 MDHl PKM2 MEl ALDOB GOTl MDH2
PGKl TPIl GOT2 ALDOA PKLR GPT GRCC9 ME3 ALDOC FBPl MAP00720_Reductive_carboxylate_cycle_CO2_fϊxation GenMAPP ACO2 IDHl MDHl MDH2 FH
ACOl IDH2
MAP00740_Riboflavin_metabolism BLACK ACPI ACP5 ACP2 ACPP ACPT TYR MAP00760_Nicotinate_and_nicotinarnide_metabolism BLACK NT5C1B NP NMNATl NNMT
AOXl QPRT MAP00790_Folate_biosynthesis GenMAPP ALPPL2 DHFR FPGS PTS QDPR ALPL
ALPI MTHFDl TYMS GGH GCHl ALPP
MAP00860_Poφhyrin_and_chlorophyll_metabolism GenMAPP CPO HMBS BLVRA PYCS
ALAD ADH6 UGT2B15 HMOXl FDXR GUSB CP EPRS HMOX2 UGT2B4
UROS UROD FECH HCCS BLVRB MAP00910_Nitrogen_metabolism GenMAPP CA 12 CA4 CTH CA5A GA CPSl
CA9 CA5B CAl CA14 CA8 ANKRDl AMT CA7 HAL DDX3X
CA6 GLUDl CA2 CA3 GLUL ASNS MAP00970_Aminoacyl_tRNA_biosynthesis GenMAPP KARS DARS GARS HARSL AARS
QARS NARS CARS RARS EPRS KIAAO335 HBG2 SARS MARS TARS
IARS WARS2 WARS HARS MAP03020_RNA_polymerase GenMAPP POLR2E POLR2L POLR2J2POLR2H POLR2D P0LR2A
POLRMT P0LR2I P0LR2C POLRlB P0LR2F IGFBP7 POLR2K POLR2B POLR2G DOK4
POLR2J MAP03070_Type_HI_secretion_system GenMAPP ATP6V1G1 ATP6V0A1 ATP6V1B2
ATP6V1G2 ATP6V1B1 MPP5 ATP6V0A4 ATP6AP1 ATP6V0D1 90 ATP6V0B ATP6V0E ATP6V1D ATP6V0C ATP6V1E1 ATP5E
ATP6V1C1 ATP6V1A ATP6V1F ATP6V1G3
MAPK_Cascade GO RAFl ARAFl MAP2K4MAP3K1 NRAS MAP2K3MAPK14D1S155EMAP3K3 BRAF MAP2K6MAP3K2MAPK3 JUN MAP2 MBP MAPKIORRAS MAPKl MAP2K1 ELKl PLCB3 MAP2K7
MAPKKK_cascadeGO MAP3K5DUSP4 FGFR3 MAPKAPK2 NRTN DUSP7 MAP3K3DUSP6
FGFRl mapkPathway BioCarta MAPK6 MAP3K10 TGFB2 MAP3K7MAPK14RPS6KA3 MAP2K6
RELA RPS6KA4 ATF2 MEF2D MAPKl 1 MAP3K13 MAP4K1 MAP3K8RPS6KA2 MAP3K11 TGFBRl MAP2K7RPS6KB1 MYC MAPK13MEF2B ARAFl TRAF2
MAP3K1 MKNKl RPS6KB2 CHUK GRB2 HRAS MAPK7 MAP3K14 MAP4K3
TGFB3 MKNK2 MAP3K5MAP2K2MAPK10MEF2A RPS6KA1 DAXX TGFBl MAPK8
MAX NFKBIA SPl RACl MAP3K3MAP3K6JUN MAPK3 MAP4K5PDZGEF1 MAPK4 IKBKB PAKl MAP4K4 RIPKl CEBPA MAP2K1 SHC1 MAPKAPK5 RAFl MAP2K4MAP4K2TRADD MAPK12MEF2C MAP2K3BRAF MAP3K2MAPK9 MAP3K9
MAPKAPK3 STATl MAP3K4RPS6KA5 NFKBl MAPKAPK2 CREBl MAP3K12
MAPKl PAK2 FOS MAP2K5ELK1
Matrix_Metalloproteinases BioCarta MMP3 MMPlO MMP28 TIMP4 MMP 13 MMP27 MMP 16 TIMP3 MMP9 MMP19 MMP20 MMP7 TIMPl MMP2 MMP25 MMP8 TNF MMP17 MMPI l BSG MMP24 MMP 12 TIMP2 MMP26 MMP 15 MMP 14 mcalpainPathway BioCarta PRKAR2A EGFR VIL2 PRKAR2B PXN MAPK3 PRKARlA
MYL2 CAPNl ITGBl PRKACG MYLK CXCR3 CAPN2 PRKACB PTK2
EGF HRAS ACTAl PRKARlB CAPNSl TLNl MAPKl ITGAl CAPNS2 mef2dPathway BioCarta TRB@ CALM3 PPP3CB EP300 NFATCl CABINl PRKCBl PRKCA TRA@ PPP3CC MEF2D HDAC2 CALMl CAPNSl HDACl SYTl CAPN2 CALM2 NFATC2 CAPNS2
PPP3CA methioninePathwayBLACK BCKDHB CBS BCKDK CTH MUT metPathway BioCarta PTPNI l SOSl RAPlB GABl CRK PXN HGF MAPK3 JUN
MET MAP4K1 ITGBl PIK3R1 PAKl MAP2K1 STAT3 RAFl RAPlA RASAl PTK2 GRB2 HRAS CRKL ACTAl DOCKl PIK3CA PTK2B MAP2K2MAPK1 SRC FOS
ITGAl GRF2 ELKl MAPK8 PTEN mitochondriaPathway BioCarta BIK CASP9 BIRC3 BCL2 CASP6 BAKl CYCS DFFB
ENDOG CASP7 CASP3 BIRC4 BAX PDCD8 BIRC2 CASP8 BCL2L1 DFFA DIABLO BID APAFl mitrPathway BioCarta MEF2B CAMKl MEF2C MEF2A YWHAH HD AC9 CAMKlG MEF2D
MYODl monocytePathway BioCarta ITGBl ITGA4 SELL SELP ICAMl CD44 ITGAL ITGB2 ITGAM
PECAMl SELE mprPathway BioCarta GNAIl PRKAR2A PRKACB GNGTl HRAS PRKAR2B CAPl ACTAl MAPK3 PRKARlA CDC25C CDC2 ADCYl PRKACG PINl
PRKARlB CCNBl GNAS MAPKl RPS6KA1 SRC GNBl MYTl mRNA_binding_activity BioCarta EIF4A1 HNRPAB KHDRBSl SLBP SSB FMRl
RPL35 ELAVLl GRSFl mRNA_processing BioCarta SF3B4 SFRS4 SFRS7 SFRS2IP SFPQ U2AF1 PRPF8 HNRPAl SLBP NONO SFRSI l SFRSl CUGBPl SMNDCl U2AF2 SF3A1 SLU7 CPSF6 SIPl
USP39 SNRP70 PRPF3 SFRS9 CPSF5 PRPFl 8 SFRS8 LSM5 SNRPB2 ELAVL4 MGC12538 SF3A3 KHSRP KHDRBSl SF3B3 HNRPR HNRPAO LSM3 PTBPl SFRSlO SFRS2
SPF45 FUSIPl U5-116KD SPOP SFRS5 LSMl DHX15 mRNA_splicing BioCarta SF3B4 SNRPDl SNRPG DDX23 SFPQ SFRS2IP HPRP8BP SFRSI l SNRPF SMNDCl SF3A1 USP39 SNRP70 IVNSlABP MGC12538 SF3A3
KHSRP SNRPC SNRPB SNRPD2 SNRPD3 CDC40 SNRPAl NOL3 SFRS4 SFRS7 MPHOSPHlO LSM4 U2AF1 PRPF8 NONO LOC283849 PRPF3 U2AF1L2
LSM6 PRPF18 SNRPN FLJ20511 SRP19 SNRPB2 PRPF4 NCBPl SF3B3 HNRPC
SF3A2 PPIG FMNL3 SRRMl NP220 FNBP3 PTBPl SFRSlO SFRS2 SPF45 U5-116KD DIMl LSMl PPAN mrpPathway BioCarta ABCC3 ABCBI l GSTPl ABCBl ABCCl ABCB4 mspPathway BioCarta TNF MSTl CCL2 CSFl ILlB MSTlR mta3Pathway BioCarta TUBA6 ESRl GREBl TUBA2 MTA3 HSPB2 HSPBl PDZKl TUBA3
ALDOA GAPD TUBA4 TUBA8 MTAl CTSD TUBAl mtorPathway BioCarta EIF4G2 TSCl PDPKl MKNKl EIF4B PDK2 TSC2 EIF3S10 FKBPlA AKTl EIF4G1 FRAPl EIF4E EIF4A1 RPS6 PIK3CA PIK3R1 EIF4EBP1 EIF4G3
PPP2CA EIF4A2 RPS6KB1 PTEN muscle_myosin BioCarta MYH7 MYHl MYOlA MYL3 MYL6 MYH4 MYHI l MRCL3 MYLl
MYL5 MYH8 MYL9 MYH6 MYL4 HUMMLC2B myosinPathway BioCarta GNAQ GNGTl PRKCBl PRKCA PPP IRl 2B GNA12 PRKCLl PLCBl
ARHGEFl MYL2 ROCKl GNA13 MYLK GNBl ARHGAP5 ndkDynaminPathway BioCarta CALM3 PPP3CB DNMl EPNl AP2A1 PPP3CC NMEl AP2M1
AMPH EPS 15 CALMl NME2 SYNJ2 SYTl CALM2 SYNJl PICALM PPP3CA BINl neurotransmittersPathway BLACK PNMT DBH TPHl HDC GADl TH neutrophilPathway BioCarta SELL ICAMl CD44 ITGAL ITGB2 ITGAM PECAMl SELE nfatPathway BioCarta MAPK14CALM1 PRKACC NFATC3 PIK3R1 EDNl SYTl NFATC2
RPS6KB1 CALM3 NFATCl GSK3B PRKACE S CTFl HRAS ACTAl IGFl
PIK3CA PRKARlB CAMKlG MAPK8 CREBBP PRKAR2 A CALR LIF
PPP3CC HANDl PRKAR2B NKX2-5 MAPK3 FKBPlA PRKARlA AKTl F2
FGF2 HAND2 MAP2K1 CALM2 NPPA PPP3CA RAFl PPP3CB CAMKl AGT MEF2C
CAMK4 GATA4 NFATC4 CSNKlAl MYH2 MAPKl ELSPBP 1 DTR nfkbPathway BioCarta TNF TRADD MAP3K1 CHUK NFKBIA IKBKG MAP3K7FADD TNFRSFlA
TLR4 MAP3K14 ILIA RELA TNFRSFlB IRAKI MAP3K7IP1 IKBKB
NFKBl TNFAIP2 I RIPKl MYD88 TRAF6 ILlRl ngfPathway BioCarta RAFl NGFB SOSl KLK2 HRAS GRB2 JUN MAPK3 PIK3CA
DPM2 PIK3R1 NGFR CSNK2A1 PLCGl FOS MAP2K1 SHCl ELKl MAPK8 nkcellsPathway BioCarta LAT VAVl KLRDl RACl MAPK3 ILl 8 ITGBl KLRC4 PIK3CA
PTPN6 KLRCl PIK3R1 HLA-A PTK2B PAKl MAP2K1 KLRC2 SYK KLRC3 B2M nktPathway BioCarta IL2 TGFB2 CCR3 IL4 CSF2 CCR2 CXCR3 IFNGR2 IL4R
IFNGRl IL12B IFNG CCL4 IL12RB1 IL5 IL12RB2 IL12A CXCR4 CD4 TGFB3
CCR7 CCR4 TNFSF5 CCR5 CCRl TGFBl CD28 ILl 8Rl CCL3 no 1 Pathway BioCarta PRKAR2A TNNIl PDE3A HSPCA PRKAR2B AKTl PRKARlA
PRKGl CALMl NOS3 PRKACG FLTl FLT4 BDK SYTl CALM2 PDE2A
RYR2 CALM3 CHRMl PRKACE 5 ACTAl VEGF CAVl PRKARlB CHRNAl
BDKRB2PRKG2 SLC7A1 PDE3B KDR no2ill2Pathway BioCarta CD3E ILl 2B STAT4 CD3Z IFNG NOS2A JAK2 CD2 ILl 2RBl
IL12RB2 IL12A CD4 TYK2 CXCR3 CD3G CCR5 CD3D nosl Pathway BioCarta CALM3 PPP3CB GRIN2D PRKAR2A PRKACE t GRIN2A GRIN2C
PRKCBl PRKCA PPP3CC PRKAR2B PRKARlA GRIN2B DLG4 CALMl PRKACG
PRKARlB SYTl CALM2 GRINl NOSl PPP3CA notchPathway BLACK NOTCHl PSENl FURIN DLLl RBPSUH ADAM17 nthiPathway BioCarta EP300 TNF CHUK NFKBIA MADH4 ILlB MAP3K7IL8 NR3C1
MADH3 MAP2K3 MAPK14MAP3K14 MAP2K6RELA TGFBR2 MAPKl 1 IKBKB TLR2
NFKBl MYD88 TGFBRl DUSPl CREBBP ox40Pathway BLACK TNFRSF4 IL2 TNFSF4 p27Pathway BioCarta CDKNlE ! RBXl E2F1 CKSlB SKPlA UBE2M TFDPl CULl
CDK2 CCNEl NEDD8 SKP2 RBl p35alzheimersPathway BioCarta MAPT CDK5R1 CAPNl GSK3B CAPNSl CSNKlAl PPP2CA
CSNKlDAPP CAPNS2 CDK5 p38mapkPathway BioCarta MAX TGFB2 HSPB2 MAP3K7MAPK14RAC1 MAP2K6ATF2 MEF2D
PDZGEFl RIPKl SHCl TGFBRl MAPKAPK5 MYC MEF2B MAP2K4TRAF2
TRADD CDC42 HSPBl MAP3K1 HMGNl MEF2C MKNKl HRAS GRB2 PLA2G4A
MAP3K9TGFB3 STATl MAP3K5 MAPKAPK2 DDIT3 RPS6KA5 CREBl MEF2A
DAXX ELKl TGFBl p53 signalling BioCarta BZRP WRN WTl RELA NDRG4 CCNH APEXl SIRTl CTSD
CHEKl TP53BP2MAP2K7BRCA1 MYC TNFRSFlOB TNF EP300 ACTAl TP53
KIP2 DAXX ABCBl CREBBP CASP9 STAT5A PRKCBl HIPK2 GADD45A MAP4
PMP22 PPIA PMAIPl TRAF5 PRKCG ATR CDC2 CSNK2A2 TRAFl RBl
TNFSF6 REPRIMO E1B-AP5 APAFl GTSEl NDRG2 BRAP TRAF4 BAPl TP53AP1
NDRG3 PRKDC BCL2 MTBP NUMB PRKCA CDK7 TP73 HSPA4 TEADl MDM2
EI24 HIFlA BAIl CSNK2A1 CDKN2/ TP73L CHEK2 RRM2B PML
ATM P53AIP1 ESRl CSNK2B SP1 RPLl 3 A MAPK8IP2 THRA LRDD BAX
BBC3 PRKCQ MAP2K4NDRG1 TNFAIPl FAFl RASAl E2F1 SERPINB5
FADD TTRAP WIGl GAPD THBSl TBP DPI CSNKlAl SFN NFKBl
CDKNl/ PCAF ACTB p53hypoxiaPathway BioCarta ATM HICl FHL2 HSPCA CPB2 AKTl IGFBP3 MDM2
GADD45A HIFlA NFKBIB TP53 HSPAlA CSNKlAl BAX NQOl CSNKlD
ABCBl CDKN IA MAPK8 p53Pathway BioCarta ATM BCL2 E2F1 CDK2 TIMP3 PCNA CCNEl MDM2 GADD45A
TP53 CCNDl BAX CDK4 RBl CDKNl/ APAFl par 1 Pathway BioCarta GNAQ GNAIl GNGTl M AP3K7 PRKCBl PRKCA PPP1R12B F2R
GNAl 2 F2RL3 F2 PLCBl ARHGEFl ROCKl ADCYl GNA13 PIK3CA PIK3R1
PTK2B GNBl ARHA parkinPathway BioCarta SNCAIP UBE2L6 UBE2E2 UBE2L3 PNUTLl UBE2G1 UBE2F UBLl PARK2
UBE2G2 SNCA GPR37 parkinsonsPathway BLACK PARK2 SNCA pdgfPathway BioCarta STAT5 A SOSl PRKCBl PDGFRAM APK3 JUN PDGFA PIK3R1 PLCGl MAP2K1 SHCl STAT3 RAFl MAP2K4RASA1 MAP3K1 SRF PRKCA GRB2 HRAS
JAKl STATl PIK3CA CSNK2A1 FOS ELKl MAPK8 pelpl Pathway BioCarta EP300 ESRl PELPl MAPKl SRC MAPK3 CREBBP
Pentose_Phosphate_Pathway BLACK TKT RPE G6PD PGD TALDOl PGLS RPIA pentosePathway BLACK G6PD PGD PGLS RPIA pepiPathway BioCarta ELA2B ELA2 GRN SLPI IL8 ELA3B ELA2A ELAl pgclaPathway BioCarta PPARA CALM3 PPP3CB CAMK2D MEF2B CAMKl CAMK2G
MEF2C SLC2A4 CAMK2A PPP3CC CAMK4 PPARGCl MEF2D HDAC5 CAMK2B
CALMl MEF2A YWHAH SYTl CALM2 ESRRA CAMKlG PPP3CA pitx2Pathway BioCarta EP300 GSK3B LEFl PITX2 WNTl TRRAP AXINl HTATIP FZDl
HDACl PPARBP DVLl LDBl CTNNBl APC CREBBP pkcPathway BioCarta GNAQ NFKBIΛ NFKBl PRKCA PRKCBl RELA PLCBl plcdPathway BioCarta TGM2 PRKCA PRKCBl ADRAIBPLCDI plcePathway BioCarta ADRB2 PTGERl ADCYl PRKACG PRKAR2A PRKARlB
PLCEl PRKACE I GNAS PRKAR2B RAP2B PRKARlA plcPathway BioCarta PIK3CA VAVl PIK3R1 PLCGl PRKCA PRKCBl AKTl PPLLCCBBll plk3Pathway BioCarta ATM CDC25C CNK TP53 CHEK2 YWHAH CHEKl AATTRR pmlPathway BioCarta TNF UBLl HRAS TNFRSFlA SPlOO RARA PPRRAAMM--II PPAAXX33
TNFRSFlB TP53 SIRTl RBl TNFRSF6 DAXX PML TNFSF6 CREBBP pparaPathway BioCarta PPARA CD36 NOS2A FABPl NR2F1 RELA PRKACG ACOXl
PIK3R1 NR0B2 FRA8B MYC EP300 TNF SRAl FAT PTGS2 PRKACB
STAT5B PRKCA MRPLl 1 PPARGCl CPTlB HSD17B4 PIK3CA PRKARlB
NCOR2 CREBBPPRKAR2A NCORl STAT5A CITED2 DUT NFKBIA PRKCBl SPl
HSPCA PRKAR2B MAPK3 JUN PRKARlA PDGFA INS HSPAlA EHHADH
PPARBP NCOAl DUSPl RXRA MEl APOA2 RBl MAPKl APOAl NRIPl LPL
NR1H3 ppargPathway BioCarta PPARG EP300 NCOA2 RXRA PPARBP NCOAl LPL PPARGCl
CREBBP pparPathway BLACK PPARG PPARA RXRA PPARD
Proteasome_Degradation BioCarta RPS27A PSMA4 PSMC6 PSMC3 PSMAl PSMB6 PSMD8 UBA52
PSMD2 PSMD5 PSMCl PSMA6 H2AFX UBE2D3 PSME2 PSMC2 UBE2D1 UBElL PSMB9
IFNG PSMD3 H2AFZ UBC PSMB7 PSMD4 PSMC4 MKI67 PSMC5 UBE2D2 PSMDl
PSMA7 UBEl proteasomePathway BioCarta PSMBl PSMD14 PSMB5 PSMA4 RPN2 PSMC3 PSMB2 PSMAl
PSMB7 PSMB6 PSMA5 UBE2A RPNl PSMA2 PSMB3 PSMA6 UBE3A PSMA3 PSMB4
PSMA7 UBEl pslPathway BioCarta PSENl GSK3B TCFl WNTl BTRC RBPSUHAXINl ADAM17
NOTCHl FZDl DLLl DVLl CTNNBl APC ptclPathway BioCarta CDC25C SHH CCNH CDC2 MNATl PTCH XPOl CDC25A CDC25B
CCNBl CDK7 ptdinsPathway BioCarta PFKM GSK3B PDPKl AP2A1 PFKP LYN PFKL RACl AP2M1
BTK AKTl EEAl ARFl RAB5A BAD PLCGl GSK3A PRKCZ PRKCE GRASP
PFKX VAV2 RPS6KB1 ptenPathway BioCarta CDKNlB PDPKl PTK2 SOSl PDK2 GRB2 BCARl MAPK3
AKTl ILK ITGBl PIK3CA PIK3R1 MAPKl SHCl TNFSF6 FOXO3APTEN ρyk2Pathway BioCarta SOSl PRKCBl MAPK14BCAR1 RACl MAPK3 JUN CALMl PLCGl
PAKl SYTl CALM2 MAP2K1 SHC1 RAFl CALM3 GNAQ MAP2K4MAP3K1 PRKCA
GRB2 HRAS CRKL MAP2K3PTK2B MAP2K2MAPK1 SRC MAPK8 rabPathway BioCarta RAB7 MEL RAB27A RAB11A RAB5A RAB3A ACTAl RABlA RAB9A
RAB2 RAB6A RAB4A racl Pathway BioCarta PLDl VAVl MAP3K1 PDGFRAPPP1R12B WASFl ARFIP2 RACl
TRIO CFLl CHNl MYL2 CDK5R1 LIMKl MYLK PIK3CA PIK3R1 RALBPl PAKl
NCF2 RPS6KB1 CDK5 raccycdPathway BioCarta RAFl CDKNlB E2F1 TFDPl NFKBIA CDK6 HRAS CDK2
RACl RELA MAPK3 AKTl CCNEl PIK3CA CCNDl PIK3R1 NFKBl CDK4 PAKl
RBl MAPKl CDKNlA ARHA radiation_sensitivity BioCarta ACTB ATM ATR BAX BCL2 CASPl CCNB2 CCND2
CCND3 CCNEl CDC2 CDKNlA EGFR ERBB2 GADD45A GAPD HRAS
IGFlR IGFBP3 LCMT2 MDM2 RAD50 RAD51 RBl TNFRSF6 TNFSF6 TP53 ranklPathway BioCarta TNFRSFI lA FOSLl IFNBl PRKR RELA IFNARl TNFSFI l
ISGF3G IFNAR2 NFKBl FOS TRAF6 FOSL2 MAPK8 ranPathway BioCarta CHCl RANBP2RAN RANGAPl RANBPl rarPathway BLACK RXRA CDK7 RARA rarrxrPathway BioCarta HD AC3 RXRA GTF2B RARA POLR2A NCOA3 GTF2F1 GTF2A1 NCOA2
TBP GTF2E1 ERCC3 NCOAl NCOR2 PCAF rasPathway BioCarta AKTl ARHA BAD BCL2L1 CASP9 CDC42 CHUK ELKl H2AFX HRAS MAP2K1 MAPK3 MLLT7 NFKBl PIK3CA PIK3R1 RACl RAFl RALA RALBPl
RALGDSRELA RHOA rbPathway BioCarta ATM CDC25A CDK2 CDC25B CDC2 CDC25C WEEl TP53 CDK4
YWHAH RBl CHEKl MYTl reckPathway BioCarta TIMP2 TIMP4 RECK HRAS TIMPl TIMP3 MMP2 MMP14 MMP9 reelinPathway BioCarta CDK5R1 DABl FYN VLDLR LRP8 CDK5 RELN relaPathway BioCarta EP300 TNF HDAC3 TRADD CHUK NFKBIA IKBKG FADD TNFRSFlA
RELA TNFRSFlB IKBKB NFKBl RIPKl TRAF6 CREBBP rhoPathway BioCarta ARPC4 OPHNl GSN DIAPHl ARPClA MYL2 LIMKl MYLK BAIAP2
ACTR2 ARHGAP5 PFNl ACTR3 PIP5K1BARHGAP6 ARPC3 PPP1R12B
VCL PIP5K1ACFL1 ARHGEFI l ARHGEFl ARPC2 ARPClB ROCKl ARHGAP4
ARHGEF5 ARHGAPl TLNl SRC ARHA rnaPathway BioCarta EIF2S1 TP53 NFKBIA CHUK NFKBl DNAJC3 MAP3K14 EIF2S2
RELA PRKR
SlP Signaling BioCarta MAPK6 PLCB2 GNAI2 MAPK3 AKTl PIK3C2BAKT3 MAPK4 EDG5
GNAIl RACGAPl AKT2 SPHK2 MAPK12EDG3 MAPK7 GNAI3 PLCBl SPHKl
ASAHl EDGl EDG8 MAPKl PLCB3 LOC96626 slpPathway BioCarta MBTPS2 EPLIN SREBFl MBTPSl SCAP HMGCSl LDLR SREBF2
SA B CELL RECEPTOR COMPLEXES SigmaAldrich VAVl PAPPA MAP3K1 SOSl MAPK8IP3
HRAS LYN GRB2 RACl RPS6KA3 JUN MAPK3 ATF2 VAV3 MAPKl
RPS6KA1 FOS MAP2K1 SHCl BLNK SYK ELKl VAV2 BCR
SA BONE MORPHOGENETIC SigmaAldrich BMPRl BBMPl MADH4 BMPR2 BMPRlA
MADHl MADH6
SA CASPASE CASCADE SigmaAldrich CASP9 BIRC3 SREBFl PRFl GZMB DFFB CASP7
CASP3 BIRC4 ADPRT TNFRSF6 SCAP BIRC2 CASP8 TNFSF6 CASPlO DFFA
SREBF2 APAFl
SA DAGl SigmaAldrich PDElB ESRl PLCB2 ITPKA ESR2 PDElA TRH VIP
PRL PLCBl
SA FAS SIGNALLING SigmaAldrich PDE6D CASP3 BCL2 TNFRSF6 CFLAR PI l
CASP8 CFLl TNFSF6
SA Gl AND S PHASES SigmaAldrich E2F2 CDKNlE ! E2F1 CDK2 CFLl PRBl
MDM2 TP53 ARFl CCNDl CDKN2Λ CDK4 ARF3 CDKNU NXTl
SA G2 AND M 1 PHASES SigmaAldrich CDC2 WEEl CDC25A CDC25B CDK7 CDKNlA
CHEKl NEKl
SA MMP CYTOKINE CONNECTION SigmaAldrich SELL TNF TGFB2 ILlB TNFSF8
CD44 TNFRSFlA TNFRSF8 FCGR3A IL6R TNFRSFlB ACE SPN
CSFl TGFBl
SA PROGRAMMED CELL DEATH SigmaAldrich BCL2L11 I CASP9 BCLlO BCL2 BAD
BAX CESl CASP8AP2 BCL2L1 BAKl BID APAFl
SA PTEN PATHWAY SigmaAldrich BPNTl PDKl AKT2 SOSl GRB2 RBL2 MAPK3
AKTl ILK PIK3CA AKT3 PTK2B PIK3CD MAPKl SHCl PIP3-E PTEN
SA REG CASCADE OF CYCLIN EXPR SigmaAldrich E2F2 CDKNlB E2F1 CDK2
CCNA2 PRBl CCNAl CCNEl E2F4 CCNDl CDKN2A CDK4 CCNE2
SA TRKA RECEPTOR SigmaAldrich NGFB AKT2 NTRKl SOSl GRB2 HRAS AKTl
PIK3CA NGFR AKT3 PIK3CD MAP2K2MAP2K1 SHCl CDKNlA ELKl ARHA salmonellaPathway BioCarta ARPC2 ACTR3 WASL ARPClB ARPC4 CDC42 ARPC3 WASFl RACl
ACTR2 ACTAl ARPClA sarsPathway BioCarta ANPEP GPT FBL LDHB MAPK14NCL LDHC CKM LDHA
EIF4E setPathway BioCarta APEXl PRFl HMGB2 GZMB DFFB SET ANP32A NMEl GZMA
DFFA CREBBP shhPathway BioCarta SHH PRKAR2A GSK3B GLI PRKACB PRKAR2B
PRKARlA GLI2 PRKACG SUFU SMO PRKARlB DYRKlA
PTCH DYRKlB GLI3
SIG BCR Signaling Pathway SignallingAlliance CD19 PPPl Rl 3B INPP5D VAVl SOSl
FLOT2 PPP3CC MAPK3 AKTl PTPRC CSK S0S2 MAP4K1 ITPR2 FLOTl AKT3
PIK3R1 GSK3A PIK3CD NR0B2 NFATC2 SHCl BLNK CD81 PPP3CA BCR ITPRl
RAFl PPP3CB PDKl NFATCl GSK3B AKT2 BCL2 GRB2 LYN BTK PLCG2
PIK3CA BAD CD22 CR2 MAPKl SYK ITPR3 DAGl
SIG CD40P ATHWAYMAP SignallingAlliance NFKBIA MAPK14TRAF3 MAPK8IP2 MAPK3 MAPKI l
NFKBIB PIK3R1 MAPK8IP1 PIK3CD TNFRSF5 SYTl NFKB2 TRAF6 MAP2K7
MAPKAPK5 DUSPl MAPK13MAP2K4TRAF2 TRAF5 IKBKG MAPKl 2NFKBIL2 MAPK8IP3 NFKBIE MAPK9 PIK3CA GORASPl MAPK10NFKB1 MAPKl NFKBILl MAPK8 SIG_CHEMOTAXIS SignallingAlliance ANGPTL2 WASL PAK4 PPPl Rl 3B RHO
GDIl AKTl PAK3 LIMKl MYLK PAK6 ITPR2 AKT3 PIK3R1 PIK3CD PAKl ACTR2 ITPRl ACTR3 PDKl AKT2 RACGAPl CDC42 INPPLl CFL2 WASFl PITX2 GDI2 MYLK2 PAK7 CFLl BTK SAG RPS4X ARHGEFl 1 ROCK2 ROCKl PIK3CA ARHGAP4 PlOl-PBK ARHGAPl PAK2 ITPR3 PTEN PIK3CG
SIG_IL4RECEPTOR_IN_B_LYPHOCYTES SignallingAlliance PPPl Rl 3B SOSl MAPK3 AKTl MAP4K1 SOS2 PIK3R1 AKT3 GSK3A PIK3CD SHCl SOCSl IL4R IRSl RAFl PDKl GSK3B AKT2 BCL2 GRB2 STAT6 JAKl JAK3 PIK3CA IRS2 BAD MAPKl SIGJnsulinReceptorPathwaylnCardiacMyocytes SignallingAlliance YWHAZ LNPEP SLC2A4 FLOT2 PSCD3
RPS6KA3 RPS6KA2 PIK3R1 PPYRl YWHAH IRSl RPS6KB1 SERPINB6
PDKl GSK3B AKT2 IGFBPl CDC42 GRB2 SORBSl YWHAQ PIK3CA CDKN2A RPS6KΛ1 SOSl MΛPK3 YWHAE PARD3 AKTl BRD4 S0S2 PTPNl AKT3
FLOTl GSK3A PIK3CD SHCl FOXOIARAFI CBL F2RL2 INPPLl CAPl IRS4 YWHAB PARD6AIRS2 SFN MAPKl YWHAG PTEN
SIG_PIP3_signaling_in_B_lymphocytes SignallingAlliance CD 19 PPPl Rl 3B VAVl FLOT2
PSCD3 GABl RPS6KA3 AKTl PTPRC RPS6KA2 ITPR2 FLOTl AKT3
NR0B2 FOXO3ABCR RPS6KB1 PREXl ITPRl PDKl AKT2 LYN PITX2
BTK SAG PIK3CA PLCG2 P101-PI3K CDKN2A RPS6KA1 TEC
PHFI l DAPPl SYK ITPR3 PTEN SIG PIPSSIGINCARDIACMYOCTES SignallingAlliance YWHAZ SLC2A4 PSCD3 RPS6KA3
CREB3 PAK3 MET PAK6 RRPPSS66KKAA22 CREB5 YWHAH IFI27 IRSl RPS6KB1
MYC PREXl ERBB4 PDKl GGSSKK33BB AAKKTT22 CDC42 IGFBPl PTK2 GRB2 CDK2
YWHAQ NOLCl IGFl PIK3CA CDKN2A RPS6KA1 BCL2L1 PAK4 PPP1R13B
SOSl GABl PARD3 YWHAE AKTl FRAPl SOS2 GADD45A PTPNl AKT3
GSK3A PIK3CD PAKl SHCl FOXO3 ATSCl CDKNlB EBP F2RL2 INPPLl
TSC2 IRS4 PAK7 YWHAB PARD6AIRS2 BAD P101-PI3K SFN CREBl
PAK2 PTEN YWHAG
SIG_Regulation_of_the_actin_cytoskeleton_by_Rho_GTPases SignallingAlliance ANGPTL2 WASL PAK4 FSCN2 FLNA PFN2 RHO GDIl AKTl PAK3 LIMKl MYLK PAK6
PAKl FSCNl PFNl ACTR2 ACTR3 CDC42 ACTGl CFL2 WASFl GDI2 MYLK2 PAK7 CFLl FSCN3 RPS4X ROCK2 ROCKl VASP MYH2 PAK2 ACTG2 FLNC skp2e2fPathway BioCarta CCNAl CCNEl E2F1 SKPlA TFDPl CULl CDK2 RBl SKP2 CDC34 slrp2Pathway BLACK TGFB2 TGFBRl TGFB3 TGFBl slrpPathway BioCarta BGN DSPG3 DCN LUM FMOD KERA soddPathway BioCarta TNFRSFlB TNF TRAF2 BIRC3 TRADD BAG4 FADD RIPKl
TNFRSFlA CASP8 sppaPathway BioCarta RAFl GNAIl GNGTl PTK2 PRKCA PRKCBl HRAS F2R PLA2G4A
MAPK3 F2RL3 F2 PLCBl ITGBl TBXASl MAPKl PTGSl SRC ITGAl MAP2K1 GNBl SYK spryPathway BioCarta RAFl EGFR RASAl CBL EGF SOSl GRB2 HRAS SPRY2
MAPK3 SPRYl SPRY3 PTPRB MAPKl SRC MAP2K1 SHCl SPRY4 srcRPTPPathway BioCarta CDC25C CDC2 CDC25A PRKCA CDC25B GRB2 CCNBl PRKCBlSRC
PTPRA CSK ST_ADRENERGIC Signalling Transduction KE EGFR GNA15 MAPK14AKT1 CCLl 3 ITPR2
PIK3R1 PIK3CD CCLl 5 APC PTXl ITPKB ITPRl RAFl GNAI l GNAQ GNAIl
KCNJ9 CAMP PITX2 BRAF KCNJ5 AR BF PTX3 ASAHl PIK3CA MAPKlO
ITPKA MAPKl SRC KCNJ3 GAS CCL 16 DAGl ITPR3 PHKA2 ST_B_Cell_Antigen_Receptor Signalling Transduction KE CDl 9 PPPl Rl 3B VAVl NFKBIA
SOSl PAG AKTl CSK SOS2 NFAT5 NFKBIB AKT3 PIK3R1 PIK3CD MAP2K1
SHCl BLNK NFKB2 ITPKB BCR RAFl EPHB2 AKT2 SERPINA4 NFKBIL2
GRB2 LYN NFKBIE BTK PLCG2 PIK3CA PI3 BAD MAP2K2ITPKA NFKBl
MAPKl SYK NFKBILl DAGl ST_Dictyostelium_discoideum_cAMP_Chemotaxis_Pathway Signalling Transduction KE ANGPTL2
PDE3A GCA MAPK3 AKTl SGCB ITPR2 PIK3R1 PIK3CD PAKl MAP2K1 NR1I3
ACTR2 ITPKB PIK3C2G ACTR3 ITPRl DGKA PSMEl ETFA RPS4X BF
PIK3CA VASP PI3 ITPKA MAPKl PDE3B PLDN DAGl ITPR3 ITGA9 RIPK3 ST_Dictyostelium_discoideum_cAMP_Receptor_G_Protein_Independent_Pathways BLACK COPEB PSMEl
MAPKl NR1I3 ST_Differentiation_Pathway_in_PC12_Cells Signalling Transduction KE EGR3 PTPNI l NTRKl TUBA3
RPS6KA3 SH2B CREB3 MAPlB PACAP MAPK8IP2 JUN MAPK3 AKTl
MAPK8IP1 PIK3R1 EGRl PIK3CD CREB5 TERF2IP SHC1 MAP2K7TH PIK3C2G
GNAQ MAP2K4MAPK8IP3 CAMP CRKL BRAF MAPK9 FRS2 ASAHl PIK3CA
EGR4 MAPK10ATF1 CREBl MAPKl SRC GAS ELKl DAGl GRF2 OPNlLW
EGR2 MAPK8 CREBBP
ST_ERKl_ERK2_MAPK_Pathway Signalling Transduction KE SOSl RPS6KA3 CREB3 TRAF3 MAPK3 EIF4E SOS2 MAP3K8RPS6KA2 EEF2K CREB5 MAP2K1 SHCl COPEB
RAPlA ARAFl DUSP4 MKNKl GRB2 DUSP9 BRAF HTATIP MKNK2 BAD MAP2K2
NFKBl ATFl CREBl MAPKl RPS6KA1 MOS DUSP6
ST_Fas_Signaling_Pathway Signalling Transduction KE TUFM VIL2 SMPDl MET NFKBIB CASP3
ADPRT NR0B2 PFNl CAD MAP2K7EPHB2 TRAF2 HSPB 1 MAP3K1 NFKBIL2 MAPK8IP3 HRB BAKl ROCKl MAP3K5TP53 MAPK10TNFRSF6 DAXX
DIABLO MAPK8 EGFR NFKBIA DEDD2 PFN2 BFAR ILIA MAPK8IP2 TPX2 FAIM2 MCP NFAT5 MAPK8IP1 PTPN 13 BIRC4 BAX RIPKl CASP8 NFKB2 CASPlO CDK2AP1 MAP2K4FAF1 ALG2 CD7 FADD IL8 NFKBIE TNFRSF6B BTK MAPK9 DEDD CSNKlAl CASP8AP2 RALBPl NFKBl MAPKl FREQ NFKBILl DFFA
ST_G_alpha_5_Pathway Signalling Transduction KE RAFl EPAC CAMP BRAF BFAR CREB3 BF ASAHl SNX13 CREB5 CREBl MAPKl SRC TERF2IP GAS GRF2
ST_G_alρha_i_Pathway_ Signalling Transduction KE RAPlGAl EGFR PLCB2 SOSl AKTl SOS2 ITPR2 AKT3 PIK3CB SHCl TERF2IP STAT3 DRD2 ITPKB ITPRl RAFl EPHB2 AKT2 KCNJ9 GRB2 PITX2 BRAF KCNJ5 BF PLCBl RGS20 ASAHl PI3 ITPKA PLCB4 MAPKl SRC KCN J3 PLCB3 DAGl ITPR3
ST_G_Protein_Independent_7_Transmembrane BLACK EPHB2 CXADR MAPKl SOATl ST_G_Protein_Independent_7_Transmembrane_Receptor_Signaling BLACK EPHB2 CXADR MAPKl SOATl ST_Gal2_Pathway Signalling Transduction KE PLDl RAFl EPHB2 VAVl PTK2 F2RL2 MAPK7
BTK JUN PLD3 BF F2RL3 F2 DLG4 MYEF2 PLD2 RASALl MAPKl
SRC TEC MAP2K5MAPK8 F2RL1 ST_Gal 3_Pathway Signalling Transduction KE RDX NFKBIA AKTl TBXA2RNFKBIB AKT3 PIK3CB
NFKB2 PLDl MAP2K4PDK1 AKT2 CDC42 SRF BCL2 MAP3K1 PTK2 IKBKG
SERPINA4 NFKBIL2 NFKBIE BF PLD3 ARHGEFI l ROCK2 LPA
DLG4 ROCKl MAP3K5GNA13 PRKCM PI3 PLD2 NFKBl NFKBILl MAPK8
PHKA2 ST_Gaq_Pathway Signalling Transduction KE NFKBIA AKTl VNlRl NFKBIB ITPR2 AKT3 PIK3CB
NFKB2 ITPKB PLDl ITPRl GNAQ PDKl AKT2 IKBKG NFKBIL2 NFKBIE
PITX2 ADRBKl PLD3 NFKBl PLD2 ITPKA NFKBILl DAGl
ITPR3 PHKA2 ST_GRANULE_CELL_SURVIVAL_P ATHWAY Signalling Transduction KE IL8RB CREB3 JUN
MAPK8IP2 PACAP MAPK8IP1 CASP3 CREB5 ADPRT APC MAP2K7ITPKB
GNAQ EPHB2 MAP2K4CXCL2 MAPK8IP3 CAMP CERK MAPK9 ASAHl MAPKlO
ITPKA CREBl MAPKl FOS DAGl MAPK8 STJLJ 3J3ATHWAY Signalling Transduction KE IL13 IL13RA2 JAK2 IL13RA1 TYK2 IL4R
JAKl STJntegrin_SignalingJJathway Signalling Transduction KE ANGPTL2 PAK3 GRLFl ITGA4
ILK MRAS PAK6 MAP3K11 ITGA5 TERF2IPACTR2 MAP2K7ITGA6 ABLl
EPHB2 AKT2 CDC42 ITGAlO PTK2 MAPK8IP3 GRB2 ITGA3 ROCKl CAVl
PIK3CA PLCG2 PKLR ACKl CDKN2A MAPKIOTLNI SRC ITGAl FYN
P4HB MAPK8 PAK4 ARHGEF7 ITGA2 ITGB3BP RALA ITGA8 SOSl
BCARl CRK RHO MAPK8IP2 AKTl ACTNl SOS2 MYLK MAPK8IP1
AKT3 PLCGl PAKl ITGA7 PIK3CB CSElL SHCl ARHGEF6 GRAF ITGAl 1
RAFl DDEFl ACTR3 MAP2K4BRAF MYLK2 MAPK9 PAK7 ZYX R0CK2 WAS
DOCKl VASP GRB7 MAPKl PAK2 GRF2 ITGA9 TLN2 PTEN STJnterferon_gammaJ3athway Signalling Transduction KE STATl PLA2G2A IFNG JAK2
CISH REGlA PTPRU IFNGRl JAKl STATIPl STJnterleukin ^_13J>athway Signalling Transduction KE ILl 3 IL13RA2 JAK2 IL13RA1 TYK2 IL4R
JAKl STJnterleukin_4J5athway Signalling Transduction KE PPPl Rl 3B INPP5D JAK2 SOSl IL4
IL2RG AKTl SOS2 AKT3 NR0B2 SHCl IARS IL4R RPS6KB1 AKT2
SERPINA4 GRB2 IL13RA1 STAT6 TYK2 JAKl JAK3 PIK3CA PI3 CISH
SRC STJak STAT Pathway Signalling Transduction KE JAK3 PIASl JAK2 CISH REGlA PTPRU
PIAS3 SOATl JAKl STJNK JHAPK _Pathway Signalling Transduction KE MAP3K10 DUSP8 PAPPA MAP3K7GAB1
MAP3K3JUN AKTl ATF2 MAP3K13 GADD45A NFATC3 MAP3K7IP1
NR2C2 MAP3K11 SHCl TRAF6 MAP2K7DLD MAP2K4GCK DUSPlO DUSP4
CDC42 MAP3K1 MAPK7 MAP3K2MAPK9 MAP3K9MAP3K7IP2 ZAK MAP3K5TP53
MAP3K4MYEF2 MAPK10MAP3K12 ILlRl MAP2K5MAPK8
ST JVfONOCYTE AD P ATHWAY Signalling Transduction KE RACl RHO AKTl ITPR2 APC ADRBl PTXl ITPRl GNAQ GNAIl EPHB2 KCNJ9 CAMP PITX2 PLB KCNJ5 BF HTATIP PTX3 ASAHl CAV3 DLG4 RYRl MAPKl KCNJ3 GAS DAGl ITPR3
ST_p38_MAPK_Pathway Signalling Transduction KE MAP3K10 MAP3K7MAPK14MAP2K6CREB3
AKTl MAPKl 1 EIF4E GADD45A MAP3K7IP1 EEF2K CREB5 NR2C2 TRAF6 MAPKAPK5 DUSPl MAPK13MAP2K4DUSP10 CDC42 HSPBl SRF MKNKl MAPK 12
MAP2K3 MAP3K7IP2 MKNK2 MAP3K5MAP3K4MYEF2 MAPKAPK2 NFKBl ATFl
CREBl MAPKl ILlRl ELKl ST_PAC1_RECEPTOR_P ATHWAY Signalling Transduction KE GNAQ ITPKA CAMP GAS PACAP
DAGl ITPKB ASAHl ST_Phosphoinositide_3_Kinase_Pathway Signalling Transduction KE YWHAZ Al BG PPP 1 Rl 3B
INPP5D SOSl PSCD3 RPS6KA3 YWHAE AKTl SOS2 RPS6KA2 AKT3
CSL4 GSK3A YWHAH P14 SHCl IARS RPS6KB1 FOXO1APDK1 GSK3B
AKT2 DAF IGFBPl GRB2 BTK YWHAB YWHAQ PIK3CA BAD CDKN2A
SFN RPS6KA1 TEC DAPPl PTEN YWHAG
ST STAT3 Pathway Signalling Transduction KE JAK3 JAK2 CISH SRC REGlA PTPRU
IL6 PIAS3 STAT3 JAKl IL6R
ST T Cell Signal Transduction Signalling Transduction KE LAT PAK4 ZAP70 VAVl NFKBIA
CTLA4 SOSl GRAP2 LCK LCP2 PAG PTPRC PAK3 CSK S0S2 NFAT5
NFKBIB PAK6 NCKl PLCGl PAKl ITK CD3D NFKB2 ITPKB RAFl RASGRP3
EPHB2 CBL NFKBIL2 GRB2 NFKBIE RASGRP2 PAK7 RASGRPl
ITPKA NFKBl MAPKl RASGRP4 PAK2 FBXW7 DTYMK NFKBILl DAGl
CD28
ST Tumor Necrosis Factor Pathway Signalling Transduction KE NFKBIA MAP3K7TNFRSF1A MAP3K3
JUN TNFRSFlB NFKBIB CASP3 BAG4 NR2C2 BIRC2 CFLAR RIPKl CASP8
NFKB2 TNF MAP2K4BIRC3 TRAF2 TRADD IKBKG NFKBIL2 FADD NFKBIE
HRB RALBPl NFKBl TNFAIP; S NFKBIL 1
ST_Type I Interferon Pathway Signalling Transduction KE STATl ISGF3G STAT2 REGlA TYK2
PTPRU IFNBl IFNARl JAKl
ST Wnt beta catenin Pathway Signalling Transduction KE PSENl CERl DKK4 NKDl SFRPl
LAMRl NKD2 AKTl ANKRD6 AKT3 GSK3A MVP TSHB IDAX APC
CTNNBl FRATl FSTLl GSK3B AKT2 C22orf2 AXINl DKK3 WIFl DKK2 PINl
AXIN2 CSNKlAl DVLl DKKl SENP2 LRPl PTPRA DACTl
ST Wnt Ca2 cyclic GMP Pathway Signalling Transduction KE ITPRl PDE6H CAMK2D PDE6D
CAMK2G CAMK2A PDE6C BF PDE6B TF CAMK2B NFAT5
ITPR2 PDE6A ITPKA SLC6A1: 5 PDE6G DAGl ITPR3 ITPKB stat3Pathway BioCarta JAK3 JAK2 MAPKl TYK2 MAPK3 STAT3 JAKl FRAPl stemPathway BioCarta IL2 CSF3 IL9 IL5 IL8 CD4 IL4 IL3 CSF2
CD8A ILI l IL7 CSFl EPO IL6 stressPathway BioCarta TANK NFKBIA MAPK14TNFRSF1A MAP2K6JUN RELA CRADD
IKBKB RIPKl TNF MAP2K4TRAF2 TRADD MAP4K2MAP3K1 IKBKG CHUK MAP2K3
MAP3K14 NFKBl ATFl CASP2 MAPK8 LTA tall 1 Pathway BioCarta TRAF2 TRAF5 CHUK MAPK14MAP3K14 TRAF3 RELA TNFSF 13B
TNFRSF 13C TNFRSF 13B TNFRSF17 NFKBl TRAF6 MAPK8 TNFSFI: 5 tcapoptosisPathwayBioCarta CD3E TRB@ CD3Z CD3G TNFRSF6 CCR5 TRA@ CD3D
CD4 TNFSF6 CD28 tcraPathway BioCarta TRB@ CD3E HLA-DRA ZAP70 CD3Z TRA@ LCK CD4
PTPRC CD3G CD3D FYN HLA-DRBl tcrMoleculePathway BLACK CD3E TRB@ CD3Z CD3G TRA@ CD3D tcrPathway BioCarta CD3E LAT CD3Z ZAP70 PTPN7 VAVl NFKBIA SOSl PRKCBl
PPP3CC RACl LCK RELA JUN MAPK3 CALMl NFATC3 PIK3R1 CD3G PLCGl
SYTl CALM2 MAP2K1 CD3D NFATC2 SHCl PPP3CA CALM3 RAFl TRB@ PPP3CB
MAP2K4NFATC1 RASAl MAP3K1 HRAS GRB2 PRKCA TRA@ PIK3CA NF ATC4 NFKBl
FOS FYN ELKl MAPK8 tcytotoxicPathway BioCarta TRB@ CD3E CD3Z CD2 TRA@ THYl PTPRC CD3G CD8A
ICAMl CD3D ITGB2 ITGAL CD28 telPathway BioCarta IGFlR EGFR TERT KRAS2 BCL2 PRKCA XRCC5 HSPCA POLR2A
G22P1 AKTl TEPl TP53 TERFl TNKS RBl PPP2CA MYC tercPathway BioCarta NFYC RBl SPl SP3 NFYB NFYA tertPathway BioCarta TP53 MAX HDACl SPl SP3 WTl MYC ZNF42
TGF Beta Signaling Pathway BioCarta RUNX3 LIF RUNX2 OAZ MADH4 MADH3 JUN
TGIF MAPK3 FST FKBPlA MADH6 TGFBR3 ZFHXlB TFE3 ITGB6 MADHl ENG
CTNNBl TGFBRl STAT3 SKIL SERPINEl NOG TNF MADHIPIFNG EGF
LEFl MADH7 MAPK9 TGFBR2 FOXHl STATl MADH2 THBSl INHBA SKI SPPl
NFKBl MADH5 FOS BMP4 TGFBl CREBBP tgfbPathway BioCarta EP300 MADHIPTGFB2 MADH4 MAP3K7MADH3 MADH7 MAPK3 TGFB3
TGFBR2 MADH2 CDHl MAP3K7IP1 MAP2K1 TGFBRl APC SKIL TGFBl CREBBP thlth2Pathway BioCarta IL2 IL12B HLA-DRA IFNG IL12RB1 IL12RB2 IL12A IL4
ILl 8 CD86 TNFSF5 IFNGR2 TNFRSF5 HLA-DRBl IL4R CD28 IL2RA
IFNGRl ILl 8Rl thelperPathway BioCarta TRB@ CD3E CD3Z CD2 TRA@ THYl CD4 PTPRC CD3G ICAMl CD3D ITGB2 ITGAL CD28 tidPathway BioCarta TNF IFNG JAK2 NFKBIA TNFRSFlA RELA WTl TNFRSFlB
DNAJA3 TP53 IKBKB LIN7A HSPAlA NFKBl IFNGR2 RBl USHlC IFNGRl TIP-I tnf and fas network BioCarta TNF TRAF2 TRAF5 TANK TNFRSFlA TRAF3 TNFSFlO
SMNl GAPD TNFRSFlB TRIP BIRC4 TRAFl TNFAIP3 TNFRSF6
BIRC2 DAXX BIRC5 BIRCl TNFSF6 TRAF6 ACTB tnfrl Pathway BioCarta LMNB2 MAP3K7 ARHGDIB TNFRSFlA JUN CRADD CASP3
ADPRT BAG4 PAKl RIPKl CASP8 LMNA TNF PRKDC MAP2K4TRAF2 TRADD
MAP3K1 SPTANl FADD LMNBl MADD DFFB RBl PAK2 CASP2 DFFA MAPK8 tnfr2Pathway BioCarta IKBKAP TRAF2 TANK MAP3K1 IKBKG CHUK NFKBIA MAP3K14
TRAF3 RELA TNFRSFlB IKBKB TRAFl NFKBl TNFAIP3 RIPKl DUSPl
T JL TlAA tobl Pathway BioCarta CD3E TRB@ IL2 CD3Z TGFB2 IFNG MADH4 MADH3 TRA@
IL4 TGFB3 TGFBR2 TOB2 CD3G TOBl TGFBR3 CD3D TGFBRl CD28 TGFBl
IL2RA tollPathway BioCarta PPARA TLR9 PGLYRPNFKBIA MAP3K7MAPK14MAP2K6RELA PRKR
JUN CD14 IRAKI MAP3K7IP1 IKBKB TLR2 TLR7 TLRlO MYD88 TRAF6
TOLLIP M AP2K4 SITPEC MAP3K1 IKBKG CHUK MAP2K3TLR4 MAP3K14 LY96
MAP3K7IP2 TLR3 NFKBl TLR6 FOS TIRAP ELKl MAPK8 torPathway BLACK IDHl ACOl IDH2 tpoPathway BioCarta RAFl MPL STAT5A RASAl JAK2 SOSl PRKCBl GRB2 STAT5B
HRAS PRKCA JUN MAPK3 STATl PIK3CA PIK3R1 CSNK2A1 PLCGl FOS
MAP2K1 THPO SHCl STAT3 trkaPathway BioCarta NGFB NTRKl SOSl KLK2 PRKCBl GRB2 HRAS PRKCA AKTl
PIK3CA DPM2 PIK3R1 PLCGl SHCl tRNA Synthetases BioCarta KARS DARS VARS2 LARS GARS HARSL YARS AARS QARS
KIAA1522 NARS CARS RARS EPRS SARS MARS TARS IARS WARS tspl Pathway BioCarta THBSl CD36 CASP3 MAPK14FOS JUN FYN tubbyPathway BioCarta GNAQ CHRMl GNGTl GNBl PLCBl HTR2C TUB tumor supressor BioCarta MADH4 IRFl WTl BRCA2 CDKN2D CCL26 APC TGFBRl
LCMT2 BRCAl EP300 CDKNlE i TSC2 CDKNlC CFLl TGFBR2 GAPD
VHL TP53 MSH2 RBl NF2 OPNlLW CREBBPACTB PTEN ucalpainPathway BioCarta ACTN3 ITGB3 PTK2 SPTANl VIL2 ACTN2 RACl PXN ACTAl
ACTNl CAPNl ITGBl CAPNSl TLNl SRC ITGAl CAPNS2 ARHA ureacyclePathway BioCarta GLS ASL GOTl GLUDl ARGl CPSl ASS vegfPathway BioCarta EIF2S1 EIF2B1 EIF2B4 PRKCBl PXN NOS3 PIK3R1 FLTl FLT4
PLCGl EIF2B5 EIFl SHCl EIFlA PTK2 PRKCA EIF2B2 HRAS EIF2S2 ARNT
VEGF EIF2B3 VHL HIFlA PIK3CA EIF2S3 KDR ELAVLl vifPathway BLACK HCK CXCR4 CD4 vipPathway BioCarta PRKAR2A EGR3 NFKBIA PPP3CC PRKAR2B RELA PRKARlA
CALMl PRKACG VIPR2 PLCGl SYTl CALM2 NFATC2 MYC PPP3CA CALM3
GNAQ PPP3CB NFATCl PRKACE ( MAP3K1 CHUK VIP PRKARlB NFKBl
EGR2 vitcbPathway BioCarta COL4A3 SLC2A1 COL4A1 SLC2A3 COL4A5 COL4A6 COL4A2 SLC23A2
SLC23A1 COL4A4 P4HB vobesityPathway BioCarta PPARG TNF RXRA RETN NR3C1 HSDI lBl LPL APMl
VOXPHOS BioCarta QP-C ATP5J2 NDUFS2 NDUFC2NDUFA10 NDUFB8UQCRFS1
ATP5J NDUFA2MBD3 NDUFB6UQCRC2UQCR NDUFABl MGC40084 NDUFB7
C0X15 ATP5C1 COX5A UQCRB COX6A2NDUFA6ATP5I BCSlL NDUFS7 NDUFB4 NGFRAPl NFKBIL2 CYB5 NDUFCl C0X5B ATP5B CKAPl C0X7A1 LOC56901 CYCl
CYCS NDUFS8 ATP5G3 ATP50 SDHD NDUFA5ATP5F1 ATP5G2 NDUFB2BCL2L1 COX7A2L NDUFA7NDUFB5ZNF183 NDUFSl C0X8 UQCRH COX6C NDUFA8PET112LSDHB NDUFB3 NDUFS4 NDUFA9COX4I1 ATP5L NDUFS6 COX6A1 COX7C CNOT7 NDUFB I NDUF A3 COX7A2
ATP5H SURFl NDUFS5 ATP5G1 SDHA SURF2 NDUFA4COX7B GRIM19 COXlO SDHC
C0X6B NDUFS3 HSPC051 UQCRCl COXI l ATP5E ATP5D
Wnt Signaling BioCarta WNT10AWNT4 FZD8 WNT5A WNT10BWNT2 WNT3 PRKCZ PRKCE
CTNNBl I MYC FZDlO PPP2R5C GSK3B FZD9 SFRP4 PLAU PRKCA AXINl
WNT2B PRKCM MAPK10WNT5B TCF7 FZD3 RACl CCND2 JUN WNT7A PRKCH
FZD5 CCNDl PAFAHlBl FZD6 APC FRATl PRKCQ CSNKlE DVL2 WNT7B
DVL3 WNTI l DIPA PRKCG MAPK9 FBXW2 PRKCD PPP2R5E DVLl FZD2
WNT6 CCND3 PRKCI ARHA WNTl 6 LDLR wntPathway BioCarta MADH4 MAP3K7CTBP1 WNTl MAP3K7IP1 CCNDl HDACl CSNKlD
APC CTNNBl FRATl MYC GSK3B NLK TCFl BTRC AXINl WIFl TLEl
PPARD FZDl CSNK2A1 CSNKlAl DVLl PPP2CA CREBBP
FA Manually Curated ACADL HADH2 DCI FACL2 ACAA2 HADHB NBSl DECRl ECHSl ACADM 384D8-2 HADHA CPTlB BC002942 CPTlA ACADVL CPT2 ACATl
CRAT ACADS AMACR ACADSB HADHSC
GLUCO Manually Curated PFKM FBP2 GPD2 MDHl ALDOB PGKl ALDOA ENOl ENO2
LDHB ME3 ENO3 PCK2 GPDl LDHA GAPDS MEl MDH2 GK CD4
TPIl LDHC GPT PC GPI GRCC9 PCKl ALDOC PGAM2 ME2 BID
FBPl
GLYCOGEN Manually Curated AGL PPP1R3A PYGM GSK3B SLC37A^ I PPPlCC
KIAAl 026 PPPlCB GYG2 GYS2 PYGL PPPlCA GYG C20orfl77 PPP 1R2
GYSl G6PC GBEl GAA GCKR PHKA2
GLYCOL Manually Curated PFKM GAPDS FBP2 HKl PKM2 ALDOB PGKl CD4
TPIl ENOl ALDOA PFKFB2 PGMl GRCC9 PFKFBl GPI ENO2 ENO3 ALDOC
PGAM2 BID FBPl
GO 0005739 GO DCI OKL38 FIBP ATPIFl NME4 MTHFD2 I TK2 ATP5J
PDHAl CPTlA PCK2 ACADS COX5A ATP5C1 DLD PDKl BCKDK ALDH2 MTERF
NGFRAPl S0D2 PDHX COX7A1 GPX4 CKAPl SUPV3L1 MUT SLC9A6
CPTlB UCP3 ACATE2 BCAT2 FARSL FPGS POLG BCL2L1 CRYl BID CPO
ACADL DUT MTIF2 ACP6 COX8 CYP27A1 GLYAT GATM PETl 12LGOT2
PRSS15 GCDH ENDOG SLC25A14 IDH3A ACATl CASP8 PDK3 CNOT7 MTHFDl
ACADSB COQ7 NFSl UCPl FARSl ACAA2 SLC25A12 CLPX NBSl
CPSl CS OTC SLC25A13 IDH3B BDH CYPI lB 1 COX7B COXI l
ME2 ATP5E BNIP3L DNASE2 PCCA TUFM CYPI lA 1 DLAT GA KIAA0963
DECRl IDH2 PCCB CA5B PDHB HADHA HSPA9B ARG2 BCKDHB HAXl
CYP27B1 FH DGUOK NOC4 SSBPl COX 15 CKMTl OAZIN HADHSC
ACO2 HMGCS2 BCKDHA FRDA CA5A NFKBIL2 DHODH SUCLGl
CYB5 ACADM ETFA IVD ATP5B 384D8-2 CYCl CYCS MTRFl BC002942
DBT AFG3L2 SDHD ATP5F1 WARS2 DIABLO CLN3 GPD2 PDK4 HADHB
DKFZP586D0919 SLC25A: S PMPCB SHMT2 SLC25A16 NDUFA8SDHB NDUFB3
OAT AMT ACADVL GLUDl MIPEP CYBB COX7A2 SPG7 ECHSl SDHA
POLRMT GLUD2 NT5M FDXR PC CKMT2 PDCD8 STAR SDHC MRPS31
CRAT CYBA SAST SLC25A; \ PPOX AMACR FDXl TXNRD2
GO ROSFO FOXMl CDT6 MTL5 SODl AOXl L3MBTLSGK2 DUSPl MSRA STK25
GPX3 ATOXl PDLIMl OSRl GSS NCFl SOD2 CCS PRDX2 CCL5 SCARA3
LTC4S SEPPl RPS6KA5 MPO CYBA NUDTl NCF2 human mitoDB 6 2002 Manually Curated HCLSl BZRP FIBP ATPIFl MRPSlO UQCRC2SLC25A11
ACADS DLD SHMTl PDKl NGFRAPl MRPS33 SOD2 AK3 GPX4 ACATE2
FARSL AKAPl SLC25A15 BCL2L1 CRYl TXN DIAl PYCS DUT ZNFl 83
GATM FRAPl MRPS 18A PRSS15 NDUFA9TOMM34 PDK3 ATP7B ACADSB
FARSl HSPEl SUCLA2 ACAA2 ATP5H MRPS30 CS TIMMlO SLC25A13 BDH
CYPI lB 1 ACAD8 TKl COXI l BNIP3L APAFl MCSP DNASE2 TUFM GA
MRPS 16 CA5B HADHA MRPS28 SLC25A21 MRPS35 RPL3 SSBPl NDUFABl
COX 15 NDUFB7 UQCRB HADHSC BCSlL CYB5 MRPLI l CYCS AFG3L2 ATP5F1
WARS2 TFBlM STARD3 TOMM20 CLPP SLC25A17 MCCCl NDUFB5NR3C1
NDUFSl HSD3B2 SLC25A! MRPL 15 UQCRH NDUFB3POPDC2 OGGl MRPL13 NDUFBl
SPG7 COX7A2TIMM9 GSR ECHSl HMGCL VDAC3 RPLP2 MRPLl 9 MRPL49 PC
MRPS31 PTPRA DCI NDUFS2 OKL38 MRPS 15 ETFDH SARDH UQCRFSl NDUFB8
MTHFD2 ATP5J PDHAl FACL4 LARS2 ABCB6 CPTlA GALR3 MGC40084
COX5A HSD3B1 BCKDK FACL2 TST NDUFS8 SUPV3L 1 MUT ATP5G3 UCP2
FPGS MRPS 18C FACL5 BID CPO MTCH2 CYB5-M BNIP3 GOT2 PLAB
GCDH NDUFS4 RPS3A SCP2 COX4I1 MRPL35 ATP5L CASP8 COX6A1 COX7C CNOT7
GRID2 TOMM70A MRPL2 GCK MDH2 TIMM44 ABCB8 NBSl IDH3B MRPL4
COXlO MRP63 GCAT ODCl MSCP ATP5J2 TIMM8ANDUFC2CYP11 A 1 TIMM 17A
PCCB ARG2 HSPA9B MBD3 TRAPl FH TOMM4( ) CKMTl NDUFA6HMGCS2
FRDA BCKDHA NFKBIL2 PRDX3 SUCLGl ACADM ETFA IVD MRPL33
MTRFl ABAT MAOA SDHD IMMT TFAM TAT C2orf3 BLVRA MRPL42 SLC25A3
NDUFA8AKAP10 MRPS7 SDHB OAT MFN2 AMT TIMM23 HSPAlA ACADVL
GLUDl CYBB NRFl ATP5G1 NDUFA4SLC25A1 OXCT FDXR GPT STAR
COX6B SAST MRPL39 TXNRD2OPA1 NDUFAlO TK2 MRPL48 MRPS27 ZNFI lB
PPM2C HTATSFl HCCS ATP5C1 HKl ALDH2 MTERF MRPS 17 CKAPl C10orf28
BAKl SLC9A6 UCP3 SLC25A10 MPO MUTYH NDUFB2POLG COX7A2L
ABCF2 CYPl 1B2 MTIF2 GLYAT COX8 MRPS18B C0X6C EFGl SLC25A14
ACATl ALASl SLC25A12 CLPX SLC25A20 OGDH NNT TIMM13 ATP5E
ME2 PPIF CST DLAT IDH2 PDHB BCKDHB HAXl MRPL12 NDUFB6
CYP27B1 DGUOK NDUFB4CA5A BCL2A1 DHODH COX5B ATP5B MRPS34 BC002942
GLS MPST MMRRPPLL4466 BBCCLL22LL1111 MRPL18 HADHB DKFZP586D0919 PMPCB SHMT2
SLC25A16 MRPL20 BAX NDUFS6 OXAlL ALDH4A1 SURFl VDAC2 MRPL44
MRPSI l POLRMT TXN2 PIN4 MRPL16 NDUFV2UQCRC1 SLCl A3 FDXl IDH3G ATP5D AGXT NME4 LYPLA2 CASQl ABCB7 NDUFA2HSPD1 PCK2 CYP24A1
ATP5S IVNSlABP COX6A2 ATP5I FACL6 NDUFS7 PDHX COX7A1 TOMM22
CPTlB BCAT2 PPID MRPLl 7 MRPS 14 POLG2 ACADL ACP6 CYP27A1 PETl 12L
MRPL34 DAP3 ENDOG MCFP SDS IDH3A MTCHl MTHFDl C0Q7 UCPl
NFSl RAFl GOTl CPSl OTC DNMlL COX7B PYCRl MLH3 NDUFS3 HSPAlL
AK2 PCCA KIAA0963 DECRl TIMM 17B CPT2 ME3 UQCR NOC4
OAZIN ETFB ACO2 SLC25A28 SLClAl BCL2 HLCS MRPS12 NDUFCl 384D8-2
CYCl DKFZP566E144 DBT ATP5O NDUFA5ATP5G2 UROS FECH CLN3 DIABLO
ClOorfδ GPD2 MRPS2 PDK4 NDUFA7MRPS22 DLST MAOB MIPEP NDUFA3NDUFS5
TIMM8BMRPL22 TIMM22 SDHA GLUD2 CKMT2 BAD PDCD8 FACL3 SDHC CRAT
MRPL9 CYBA MRPL24 AMACR SLC25A4 PPOX MFNl
INS Manually Curated PIGF SOSl FL0T2 CRK PRKAR2B AKTl PTPNl FLOTl NCKl INSR PIK3CB PRKCZ IRSl PDPKl AKT2 FLJ23042 CBL ARHQ INPPLl IRS4 SORBSl CD4 IGFl PTPN6 PIK3R3 NCK2 GRF2 PTEN
KET Manually Curated OXCT BCKDHB HMGCS2 BCKDHA LYPLA2 ACATl HMGCL BDH mitochondr Manually Curated BZRP FIBP ATPIFl MRPSlO FLJ20859 UQCRC2POLR1B
PEOl SLC25A11 ACADS CAD DLD PDKl NGFRAPl MRPS33 S0D2
AK3 GPX4 ACATE2 PKLR FARSL SLC25A15 BCL2L1 CRYl CABCl DIAl DUT ZNF183 GATM MRPS18A PRSSl 5 TOMM34 PECI PDK3 ACADSB DKFZP434N1235 FARSl HSPEl ACAA2 ATP5H MRPS30 SLC1A2 CS TIMMlO SLC25A13 BDH CYPI lBl TFB2M G6PD ACAD8 CASP2 COXI l BNIP3L LCAT APAFl
BIK MCSP DNASE2TUFM GA MRPS 16 CA5B HADHA MRPS28 SLC25A21 MRPS35 SSBPl NDUFABl COX15 NDUFB7UQCRB HADHSC BCSlL MAP3K1
CYB5 MRPLl 1 CYCS AFG3L2 CGI-04 ATP5F1 WARS2 TFBlM STARD3 TOMM20 SLC25A17 NDUFB5NR3C1 NDUFSl SLC25A5 MRPLl 5 UQCRH NDUFB3POPDC2 TNFRSF5 MRPLl 3 NDUFBl GNLY SPG7 COX7A2 TIMM9 ECHSl HMGCL VD AC3
MRPL19 MRPL49 PC MRPS31 PTPRA C15orfl2DCI NDUFS2 OKL38 MRPS 15 SARDH ETFDH UQCRFSl NDUFB8MTHFD2 ATP5J PDHAl LARS2 CPTlA Magmas MGC40084 COX5A MB BCKDK FACL2 TST NDUFS8 SUPV3L1 MUT ATP5G3 UCP2 LGALS3 FPGS MRPSl 8C BID CPO MTCH2 CYB5-M VAV1 YWHAE ERBB2 GOT2 GCDH NDUFS4 EHHADH COX4I1 MRPL35 ATP5L CASP8 COX6A1 COX7C CNOT7 TOMM70A MRPL2 GCK ClQBP MDH2 TIMM44 ABCB8 NBSl IDH3B MRPL4 COXlO MRP63 MSCP ATP5 J2 TIMM8 ANDUFC2 CYP 11 A 1 TIMMl 7A PCCB ARG2 HSP A9B MBD3 FH PRSS25 TOMM40 CKMTl
NDUFA6HMGCS2 FRDA BCKDHA NFKBIL2 PRDX3 SUCLGl ACADM ETFA IVD MRPL33 FXC1 MTRFl ABAT MTXl MAOA SDHD IMMT TFAM TAT C2orf3 P53AIP1 MRPL42 SLC25A3 NDUFA8MRPS7 SDHB OAT C16orf3 MFN2 AMT TIMM23 ACADVL GLUDl CYBB ATP5G1 NDUFA4POR SLC25A1
FDXR STAR COX6B GNAS SAST MRPL39 TXNRD2RPC2 NDUFAlO TK2 MRPL48 MRPS27 CYP2E1 ZNFl IB HTATSFl DCTN6 HCCS ATP5C1 PLA2G1B
HKl PYGB ALDH2 MTERF MRPS 17 TNFSFlO CKAPl BAKl C10orf28 SLC9A6
UCP3 SLC25A10 MPO NDUFB2CDC42BPB POLG ABCF2 CYPl 1B2
ADCK2 MTIF2 MT GLYAT COX8 MRPSl 8B COX6C MRPL41 EFGl SLC25A14
ACATl CAT ALASl SLC25A12 CLPX SLC25A20 NNT TIMM 13 ACAAl
ATP5E ME2 SLC30A9 SHB DLAT IDH2 PDHB YMElLl BCKDHB
HAXl MRPL12 NDUFB6CYP27B1 DGUOK SLC25A22 NDUFB4CA5A BCL2A1 DHODH COX5B ATP5B MRPS34 BC002942 CYP20A1 MPST MRPL46 MRPL18
HADHB MTX2 MTOl DKFZP586D0919 PMPCB SHMT2 SLC25A16 MRPL20 MYCBP
BAX NDUFS6 C20orfl4OXAlL ALDH4A1 SURFl VDAC2 MRPL44 MRPSI l POLRMT
TXN2 PIN4 C14orf2 MRPL16 PRKCD NDUFV2UQCRC I SLCl A3 ATP5D FDXl NME4 LYPLA2 CASQl ABCB7 NDUFA2PP HSPDl PCK2 ATP5S COX6A2ATP5I PDHX
ATPAF2 COX7A1 TOMM22 SNCA CPTlB BCAT2 PLA2G2A TP53 MRPL17
C21orf2 MRPS14 POLG2 ACADL ANXA7 MGC2615 SIRT4 ACP6 CYP27A1
PET112LNME2 FLJ10618 MRPL34 DAP3 ENDOG MCFP IDH3A MTCHl MTHFDl
COQ7 UCPl NFSl RAFl RAN CPSl MRPL3 OTC APP DNMlL COX7B CROT PYCRl NDUFS3 AK2 GRBlO PCCA KIAA0963 DECRl ECGFl CYP7A1 TIMMl 7B ME3 UQCR MRPL28 NOC4 OAZIN ETFB ACO2 SLC25A28 SLClAl BCL2 MRPS12 NDUFCl CYCl 384D8-2 DBT ATP5O NDUFA5CNNM4 ATP5G2 FECH FAM3A CLN3 DIABLO ClOorfδ GPD2 MRPS2 PDK4 NDUFA7MRPS22 MAOB MIPEP NDUFA3NDUFS5 TIMM8BMRPL22 TIMM22 SDHA FLJ20551 GLUD2 NT5M TPO CKMT2 MFTC PDCD8 SDHC CRAT MRPL9 CYBA FLJ20399 MRPL24
AMACR SLC25A4 PPOX GC Manually Curated PYGM MUC5AC DNAJDl DKFZp434O0213 NDRG4 PHYH HSPBPl
NR0B2 HSPA5 SLC25A11 ACADS DLD SHMTl HADH2 MNDA NME7 NGFRAPl
GABARAPLl S0D2 RAMP3 GPX4 GHITM CHP GNAl 3 AKAPl HMGB3 FLJl 3612 -30 PIB5PA USP8 FRAPl EROlL MRPS 18A PRSS15 MRPL40 TARBPl MAP2K1 ABCFl HSPC132 FXR2 KCNNl FARSl HSPEl SUCLA2 ME1 CS CTSF MYHI l
PSMB7 MDS029 TFB2M SFl GPI SCNlB MT2A CARHSPl DBI BNIP3L TUFM CKS2 PGKl GTPBP2 ENOl LRBA NCAMl COPS3 NDUFABl DHX16 UQCRB FLJ22555 NOLA3 UBE2B MRPLI l CYCS TCIRGl SRC FLJ 10511
CLPP PUSl ATP5A1 TBLlX NDUFB5 PGAMl SLC25A5 MRPL 15 C6orf209 LATSl
NDUFB3POPDC2 ATPlAl UPPl MRPL13 TCN2 COX7A2 HSU79266 MPP5 VDAC3
HBAl PGMl LPINl AES DFFA FAM18B MTHFD2 PDHAl SPTLC2 ULKl
NSF ITPR2 PSMA6 CPTlA FLJ20758 ITPKl KIAA0103 MARS HI l
HLA-DRA PTK9L PFKP SUPV3L1 PTGES2 EDNRA EEF1A2 E2IG5 GRCC9
DOM3Z PCKl MGC4276 BID IFRDl MTCH2 HBD CX3CL1 VIPRl CGI-128
GCHl PTDSR PLAB GCDH SLC20A1 ATP5L PSMBlO COX6 Al COX7C SlOOAl
CNOT7 MDH2 UBC F2RL2 GSS STARD7 TIMM44 GK FZD4 ARMET AKl
MRPL4 TMX2 RXRB C9orfl6 LCN7 POLR2E TIMM8AFOXM1 TIMM17A HSPA9B
PDGFRBPMMl FH SCD TOMM40 BAT3 NDUFA6S100A13 PRDX3 SUCLGl
USP2 ACADM FXCl DPYSL3 MTXl RRM2 TFRC SPINTl SPPl AGPAT3 RNF5
RTP801 DDT DRPLA GRPELl REA NDUFA8SDHB RAB31 TIMM23 SGTA LDHB
SZFl CPR2 PHLDAl DUSPl PKM2 MGC5139 SPUVE TNNI3 RPA3 OXCT
PDIP38 APBA3 KIAA0033 MGC29816 FLJ22390 MAPKAPK2 KIAA0205
UROD LSMl RANGNRF EIF4A2 GRSFl MRPL39 UMPK ABCA2 DGATl ZNFI lB
MKRN3 C7orf32 SIAT7D GOLPH3 SARA2 HCCS ATP5C1 NRPl GLRX VAMP8 MRPS 17
RTN4 TM4SF12 STK19 ACYPl GYSl DUSP6 SOD3 ADSL PDCD6 AKIP
COX8 MRPS18B SKIV2L EFGl EIF3S6IP ABHD5 FLJl 0134 HRI
FLJl 2598 GTF2H4 CDKN2D RAB40C ALASl MGC15396 TSC2 SLC25A20
CRLF3 REC14 TIMM13 IFI16 TTCl ZNF216 CKIP-I UBLl NDRG2 IDH2 COHl
C20orf45 PDHB DNAJA3 CIA30 NDUFB6AKR1B10 BACH SACM1LLCN2 ESRRA
ACTR2 STK16 MO25 COX5B MRPS34 C21orf97 SH3BGRARHD LRRFIP2MRPL46 MRPL18 COMT HADHB MTX2 DKFZP586D0919 CRMPl MRPL20 COL7A1 NPPB P4HA2 THEM2 FASTK PLA2G12 PCOLCERANGAPl PGLS GAPD TXN2 VIP32 C14orf2
NDUFV2FOS UQCRCl GBAS FDXl IDH3G ADSS ALS2CR3 ARVCF SLC2A4
SMPDl HSPDl LSM8 UNG PSCA PTPRD PPMlG RRMl COX7A1 MAL ICTl
POLR2F SLC31A1 ID2 RUVBL2PIGQ ACADL LRPPRC GATA3 PSMB5 DC13
SLC12A7 PDXK OSBPLlA FLJl 1560 MYL2 LRP5 MRPL34 SNWl
PSME3 IDH3A NFSl NFYC PTDSS2 FBSl HUMPPA CA4 KIDINS220
MGC10940 ACYP2 MGC3047 COX7B C14orf87 IINNHHBBAA NFLX CA2 ATP6V1D
APG-I NDUFS3 NINJl HSPC051 LOC123803 PPFFKKMM CHRNE ECGFl GABPA
GTPBP4 FLJl 0420 OAZIN LDHA ETFB ACO2 SSAATT GAFl PCTK3 MRPS 12
MAT2B EGLNl NDUFCl CYCl VEGF ATP2A3 CMKORl ATP5O NDUFA5FABP3
MAPK8 MRPS2 PDK4 GSTOl ARIHl SEPXl GUKl DKFZP564B167 CIAOl PCYT2
NDUFS5 BSG TIMM8B MAP2K3 SDHA TPIl PSM A5 PRDX2 ATPlBl CKMT2 PDCD8
DNAJB9 CRAT CDC34 AMACR SLC25A4 MFNl
PYR Manually Curated PPM2C PDKl PDK4 PDHA2 PDHX PDK3 PDHAl PDHB ROS Manually Curated GPXl ZNFI lB PRDX3 KIAA0963 SOD2 GPX4 PRDX6 TCA Manually Curated ACO2 SUCLA2 MDH2 SUCLGl CS IDH2 SDHA SDHB OGDH
IDH3B SDHD IDH3A FH SDHC IDH3G shhjisa Manually Curated PRKAR2A GSK3B GLI PRKACB XPOl CDK2 RASGRFl
PRKAR2B BMP2 GLI2 DYRK2 CDK8 PRKACG FGF4 DYRKlA
PTCH CCNBl GLIPRl MYC_WT Myc wild type UQCRCl YPELl KCNJlO ACTR2 KIAA0652 2 SIRT2 CASK
ZNF333 VPS45A IVNSlABP
MYC_MUT BLACK NNMT HEAB GSS RAN TIPARP
INSULIN_2F_DOWN Rome_et_al_2003 CYP4A11 MSH5 Bl TGFB2 KIAAl 117
C10orflOCNTN2 PRKR CPAl ELA3A CLTB MLL BRD4 CRYBA4FLJ10815
NIN APCL CDCl 6 TCL6 PCDH17 BCLlO KIAA0746 TOX MAD C6orf4
ALMSl FNBP3 TGM3 BCLG SH2D3C SERPINAl PRKX TRAD FBXL6 KIAA1430
MMP23B INSULIN_2F_UP Rome_et_al_2003 MSI2 PC4 UKl 14 FHL3 HK2 YWHAH ASHlL KARS
CANX PPP2R3A SCAl GLRX SARCOSIN PXMP3 ZNF9 LSM3 PAM
YWHAQ PPP1R2 GNPDAl IFITl ARCNl ATP6V1E1 HNRPDL VDACl ASCLl
NRDl SNAPAP TSGl 01 ADSL LAPTM4A SUIl PSARL SCOC DNCLl NFE2L1
PTP4A1 WBSCRl UBE2E3 FLJl 1506 AHSAl UB A2 CDK2AP1 H2AFZ
SLC25A12 BUBl TRIM32 NP220 SDBCAG84 ACP33 SH3GLB1 SET
SPS2 CLNSlA UBB TIP 120B CCL 16 GNPAT GL004 FLJl 1021 COPS5 RBXl
USP9X UBLl PRO2730 MRPS 16 QARS VPS29 HNOEL-iso ZNF44 AKAP6
PAIP2 SPARCLl MGC5508 CRIl ORF1-FL49 HADHSC CAMLG
STS OSRl NT5C3 UBE2B PTMA CMAS FAM 16AX HECTDl IL13RA1 EIF2S2 SORBSl NIFU ARPP-19PURB FEMlB IPO7 AHCYLl PGAMl PSMD 13 SDCBP UBQLNl ALDOA VIM EEFlG SNRPB2 OXAlL SERPINFl ADFP COX7A2 PDE4D HSF2
GYG GCNlLl UBE2I GMPR RPLPl GBAS NPMl ITGAE CSDA CD36 PSMD14 FNTA TIMP3 TALDOl HERPUDl JTVl HDGF C21orf7 TAF7 PRDXl S100A7 PSM A6 CAPN2 TERF2IPMGC21854 CIS PPP IRl 2A HI l FACL2 ALS2CR2
VCL TCTELl CL640 ZAK NACA CLECSF2 BTF3 PSMB4 ADHFEl TM4SF2
PLN FBP2 IHPK3 ANXA7 TM4SF3 MTCH2 G3BP DC13 UACA LAMRl GOT2 GPSN2 NDUFS4 MAP4 MORF4L2 UGP2 STARD7 ACYP2 C17orf35 RNP24 ARF4
GTF2A2 HBB SYNPO2L H2AV ODCl MAT2A ST13 YWHAG USP22 C20orfl08 PABPC4 VCP GSTA4 PRDX6 CLCN3 NCKAPl FLJ20533 UBE3A HGRG8 KIAA0830
RPL7A DREVl MGC2963 HSPC155 FLJ13456 RPL41 CFL2 USP16
SLC39A14 DPYSL3 SPOP TPMl DAGl PSMA4 ARIHl CCT8 RNFlO ATP6V0B
EPM2A LDHB LMCDl LAPTM4B UBE2V2 SLC35B1 MAOB HSPCO 16
CD59 DDXl MGC2452 SRP 14 NFIA OXCT RPS20 AKR1C2 PGRMC2 DDX48 HLA-C RAB5A BCL2L2 PUM2 LARGE PSMA3 C3orfl FLJ10081 ACTB
NFKBJNDUCED Hinata_et_al_2003 SPRRlB WNT5A MAPlB RELA ABCCl CTSE SODl CCL2 CXCL5 CFLAR TNF PLAU ILlB SOD2 FGF5 MSC RABEPl RAC2 STAT5A
IRFl ARHGDIB RACl GCHl GADD45A CXCLlO IFNAR2 GTF2H4 IL7R
CDH2 BTN3A3 CXCLl 1 KRT14 GPR37 SLC7A2 GABBRl KRTlO PMSCLl IL8 MAPK9 PTX3 TIAMl SERPINB2 ICAMl CCNBl TAPl IL6 CXCL6 ESMl ADAMTS3
FNl MMP9 EDNl CYP27B1 ITGB6 MYBLl SPTBNl EFNAl SERPINEl SELE ETSl CDH3 TNC BCL2A1 XPC OLRl SAAl TNFAIP2 NPRl ILlRN PNRCl GBPl RARRESl RELB SEC24A MMP 14 WFDC2 KRT6B IER3
NK4 CXCL3 BMP2 IL15 ILIA PLAT CSF2 FGF2 TNFAIP6 CD83 MMPl ARHE KIAA0608 HGFAC ARF6 NFKB2 CXCLl UTX KRT7 TNIPl
ERCCl RPA2 CXCL2 MAP2K3AP2B1 CCL5 CPNE5 CD9 NFKBl LITAF CCL20 TAF15 CDKNlA
NFKB_REDUCEDHinata_et_al_2003 HYALl DUSP4 RIMS2 C4BPA DAPKl RAI3 KLK6 RUNXl PPL UPKlB SULT2B1 THBSl DSG3 SCEL INA KIAA0350 CEACAM6 KLK7 ZNFl 85 RGS2 PTHLH
EMTJUP Jechlinger_et_al_2003 ADSS DCN MTHFD2 PPDDGGFFRRA/ i.DDDDRR22 SPARC ADA
VLDLR PROCR PDGFRBCD68 S100A8 CXCL5 P PTTGGSSll MMMMPP22 IIRRFF77 BCL3 GBP3 GALKl TNC COL6A2 CYPlBl CDH15 MMP12 CCMMKKOORRl1 HHIIFFllAA PRSSI l Gl P2
RRAS IFITl B2M SLC3A2 SRM SNAIl SLPI MMP 13 PLA2G7 PPIC VIM RNASET2 CDH2 PMP22 GASl UPPl CXCLl IFITM3 PCOLCE DAB2 PHGDH
SDC2 STATl CTSZ INHBA ILI l FMOl COL6A1 ASNS
EMTJDOWN Jechlinger_et_al_2003 FBP2 HMMR BCL6 FLNA STAT5A ATF3 MYH9
FOSB TIMP3 RARA IRF6 AMDl F3 PKPl EGRl TGM2 ATPlAl DUSPl
ITPRl SGK CTGF KITLG SERPINB5 ACTN4 NUMB JUP VAMP8 PADI2
KLF2 TACSTDl TGFB3 ARHGEFl NNT THBSl CDHl TIAMl GRB7
ITGB5 CTSH EGR2 HTERT_DOWN Smith_et_al_2003 ALDH7A11 PPOONN22 NME4 IDIl HEAB GM2A ABR
ALDH3A2 PTPNSl PCOLN3 RRAABBlI IIAJS L SSOORRDD KYNU FAH STAT4 POU5F1 TST
TNFSFlO SAAl A2M PAM ASAHl ILlRN GPRK5 DNA2L ATP5O TAGLN
PIK3R3 PML RIG VAV2 DUSP6 KIAA0140 CCNGl GSTOl DHCR24 UNC119
CALML3FOSB ARHGDIB GSN AKTl SRD5A1 PPP 1R7 TNFSF9 SERPINGl
EHHADH VSNLl AHCY CBRl RRAGA CD47 UGP2 TRADD XRCC5 TUBB4
PCNA APEGl ACLY AKRl C3 GAMT ANKRD 15 PGF ANX A4 TCF4 RAB40B
NID2 HTERTJUP Smith_et_al_2003 ATF3 LMO4 ch-TOG SFRSI l MTHFD2 ZNF165 HERPUDl
CCNH ZNF274 ILF2 PSMDI l HYOUl ZFP36 MADHl AHR MARS CDC6 DAF
MGEA6 TCTELl TOPl PSMD4 ICTl NFXl DRl DYRK4 SLC33A1 NFIL3
CREBBP IFRDl RBMlO TSGlOl LHFPL2 CEBPG TGIF ETV6 CCNAl MCFD2 TOMM34
SRP 19 NEK3 KIAA0063 GOTl GSS CBX5 GK STE MAPK9 R3HDM
GATA6 A2LP PYCRl DYRKlA DAP C11ORF4 XBPl ASNS RAEl
ELF4 EIF2S1 PSMD7 CTH ALKBH AARS PCCB MICA GFPTl KIAA0073
ILl 3RA2 DGUOK CDKN3 CBLB EPHA2 TNC XPC WASFl RPP30 MLHl MADH7 ILlORB COVAl EPS8 CDKN2A KIAA0092 SNRPAl NPCl BCL7B SH3BGR
EGFR CLPP PLEKHCl SCYEl ADAM8 BMP2 HlFX FGF2 SLCl A5 PPPlRI l
PIGH KLF5 DUSPl DDXlO GTF2E2 HNRPD EWSRl CXCL2 STK3 NUP88 HSF2 PPP2R2A TRPCl MRPL49 NFKBl TCEAl RDBP DCTN2 HUMAUANTIG
ANTI_CD44_UP Hogerkorp_et_al_2003 SERPINCl CAMK2D CDKL5 RGS3 ATP1A2
MAPK14ECGF1 ILIA MLLT3 STXlA SOX5 ADRB2 AQPl PLG SH3BP2 IF
ALB AFAP PYGL C18B11 GCNT2 PDE6A PIGA MITF NBLl ANTI_CD44_DOWN Hogerkorp_et_al_2003 GUCY2F SERPINAl HLCS PRDM2 PALM
EPHB3 SSTR4 MLLTlO APC PLSl LAMP2 SLC14A1 HOXA9_DOWN Dorsam_et_al_2004 IGF2 WSBl CD36 JUNB KRTl 8 SFRSI l GATA2
MAN2A2 CDC37 SBNOl SERPINB9 JUN SDCBP TPR USPl RBBP6
LYZ S100A8 SDC4 ARNTL DSIPI MYC FPRLl FCGRT GLRX SRP72 TRAP240 LYN DCT BMIl HBEl NFIA CLCN7 VHL OSBPL8 FXRl CISH DNCLI2 YWHAG
P53JJP Kannan_et_al_2001 ABCA3 ADFP APLPl ATF3 BAKl BAX BBC3 BCL6
BTG2 CDKNlA CES2 CSPG2 CTDSP2 DDB2 DGKA ENG EXT2 FEZl
FHL2 GADD45A HANI l IGFBP6 KIAA0247 LCAT MAN2B1 MDM2
NDN NHLH2 NINJl PCNA PLK3 PMAIPl POMZP3 SCGB2A2 SCRIB SMTN SURFl TMSNB TNFRSF6 ZNF7
P53_DOWN Kannan_et_al_2001 APBA2 ARL4A BIRC3 C4orf9 CCNEl CDC6 COL18A1
CPM CXADR EIF4A1 FOSL2 INA MAC30 PMP22 PPAT PURA ARL5 BRCAl GOS2 RAPJJP Peng_at_al_2002 H2BFS BARTl PLTP PDK2 DOK2 ADA CMRF35 IGL® C5orf7 APS CFLAR DAAMl TOP2A CIRBP H2AFX EIF3S6 MYC HIST2H2AA CUTLl
EMSl PDLIMl ALDH2 JUND SMAP TAFlO MEG3 ATP6AP1 CD48 CD37
BRD8 HDAC5 BRFl P8 TP53 LOC51035 ARHGAPl C6orf80 UCP2
GCN5L1 MUTYH IFITl POLD4 KCNMBl LTA ASCLl PSG7 UBE2J1 BCL6
CCNGl MS4A1 BCL7A PRKCBl TNFRSFlA SLC35E2ZFP36L1 IL2RG GMDS PPP2R5A RGSlO STAT2 HLA-DQAl IL4R EDG5 CRHR2 CAMKl GPX6 MAP4K2CENPF
NOTCH4MUSK RQCDl KIFAP3 KIAA0342 TBClDl GRINLlA KIAA1536 hnRNPA3 GNB3 CLOCK JAKl IGHG3 HIST1H2BK SPOCK2 PTK2B TKl
LRMP IGSF4 BNIP3L PIK3CG PTPN18 RWl HMMR SASHl DRAPl QSCN6 DDX46 HSRNAFEV IDH2 ASS BTG2 BASPl TCLlA TCF20 YF13H12 MGC2650 RGS13 IGLJ3 IFNGR2 HMG20B ATP6V0A2 DMBTl HAGH C5orfl3 HIST1H2BI
SSTR2 URKLl CTDSP2 MS4A2 FKBP8 HMGCS2 RASGRP3 BC-2 FLJl 3052
CBLB BCKDHA MYOlF AP4M1 HLA-F ATP2A3 EPS15 ROCKl TAZ CNAPl
UROS RELB LANCLl TNFRSF7 POU2F2 HLA-DPBl Rabl l-FIP3 CD53
EPB49 FAIM2 IGHM SLC25A6 PSCDl AKR7A2 LY86 ACADVL TNFRSF5 BRD3 RHBDLl ACINUS FANCG RTN2 HIST1H3H XK FUCAl KIAA0746
ENPP2 ERCCl CDTl TXNIP SURFl PTPRH ARPC3 EVERl HIST1H2BN HMGCL CSNKl G2 RP A3 KCNH2 HBPl KIAA0076 MTMR2 HEC POU2AF1
LKAP CD22 DVLl MDM4 GNGlO TOP3B GMPR TRO SLC38A6 CRAT
RBMS3 LAPTM5 AES RAP_D0WN Peng_at_al_2002 UMPK IFI30 RPS26 ETFl RNU3IP2 PSMDI l PSMD5
HYOUl HSPA5 ADRMl HCCS TARS TRIP13 SF3A3 HADH2 SNRPC DKFZP564F0522 ACAT2 NPM3 RTN4 FARSL TRAl TTS-2.2 EMP3 NXFl PAPOLARABGGTB AATF WBSCR22 NDUFA9CALU FKBP4 AHSAl PSMC2 CD47 CTSC HSPEl
TCPl FASN HRMT1L2 EIF4G1 FNBP3 FLJ12443 MLF2 DDX21 LIMK2 COXI l RAB14 XBPl PPIF TGDS PGKl SLC29A1 KIAA0218 PSMD8
NOL5A BYSL ARFl JTB MRPL12 ATP6V0E MGC5508 P5 KIAA0179
SSBPl HSPCl I l KPNB2 DKFZp434K1815 BCSlL DNAJAl FAM 16AX GCN5L2
CHERP PIP5K1ACYCS SSA2 DDX3X PTDSSl HB-I SNRPAl SRM CHCl HSPA8 RTCDl PITPNB PGAMl P2RX5 RBBP6 CCT4 MYCBP SLCl A5 XPO6 CAPZA2 DDX19 CTPS TDG CSElL CCNC RPP20 GORASP2 RNASEHl ALDH4A1
CCT2 KIAA0007 BCAP31 YARS PPP2R2A EBNAl BP2 BTK WDRl 8
PPIB EXTL3 CDK4 AFlQ PSMD14 GLO1 EIF2B4 WNT10BNME1 ATF5 DPH2L2 C8FW AMDl PHB NARS PA2G4 MARS UCHLl RBPlLl EIF3S9 FLJl 1126 ATP5G3 ICTl BMPl EEFlEl POLR2F ATP6V0C NUP98 ID2 RAB9P40 USPlO S100A4 SQLE HBD PSMB5 HSPCA SIT PTMS RABlA GOT2 GCDH
DAP3 NMP200 RARS IDH3A MORF4L2 SLC7A5 POLR2B GSPTl TXNL ATP 1B3
ClQBP NOLI UBE2M TIMM44 COPB2 ARMET IDH3B PTBPl COX7B RNP24 GTF2A2 NDUFS3 HBB AK2 ASNS RAEl PFKM UBE2L3 IDIl VCP TIMM 17A GM2A KPNA3 ZNF259 HSPA9B CCT6A NP C2F TUBGl CCT5 SCD TOMM40 HSPCB SREBFl CHUK PRDX3 CDC25A MRPS 12 STAU ETFA SYNCRIP CYCl
SLC39A14 HSPA4 TFRC MMP 15 ZNF294 ACVRLl SLC3A2 TEBP EIF4G2 GTF3C1
DHCR24 SAFB SDHB KIAAOl 17 PTPNl LOC84549 LDHB GARP PICALM
EBP EIF2B2 INPP5E MAPKAPK3 NMTl PTRF RNH GLUTJJP Peng_at_al_2002 PTPRT DKFZp586I1420 HEXA BARTl TRIO SSH3BP1 LGALS3BP CLN2 TOP2A TARS BHC80 MAP1LC3B NDP52 PYGB ALDH2
SMAP LPP AIMl TYK2 ACTAl VPS45A BRD8 TERF2 HDAC5 STK19 BLK C6orf80 CNIH GCN5L1 C21orf33 POLD4 RBM5 UBE2J1 CCNGl BCL7A SERPINIl RNPC2 EGFL5 VAPB KIAA0725 SUIl HRMTlLl PPP2R5A NFE2L1
RAB3GAP ADD3 CUL4B TES BTGl HMGB2 GLBl OGT PMAIPl NOTCH4 TSC2 NITl PHGDH SDBCAG84 PJA2 SF4 GNB3 PLCL2 IGHG3 KIAA0376
PQBPl PRKCI SLC30A9 SMARCBl BNIP3L CDS2 DKFZP547E1010 ATP6V0A1 RWl LRPlO HOXC5 IDH2 AARS GABARAP NCF4 CLIC4 SlOOAI l BCKDHB
HAXl IGLJ3 ENO2 HAGH GRHPR COL9A2 HADHSC CTDSP2 GSTTl BC-2
CBLB SPAG9 NFIC ZNF161 BACHl SLC43A1 KIAA0907 SARS BCL9
TNFRSF7 STXBP2 NR3C1 KIAA0053 KIAA0663 SLC1A5 HSFl PSCDl SIAHl SLC1A4 IARS P4HA2 DSIPI LYSALl KIAA0746 SLC16A3 SURFl
BMIl YARS LY96 PSCD2 HSRTSBETA TXN2 HEC ACPI FLJ21439 KIAA1055 DKFZP566A1524 ASMTL DVLl RDBP TOP3B PTPRA CLASP2 GPLDl
JMJD2 SEC14L1DOK4 VAMP3 DDX23 ATF4 ZNF297 MTHFD2 ATF5 ADA
SMTN PTPRC CPNEl IGL@ APS ITPR2 C6orfl30DAAMl PCK2 CIRBP GCHFR CLASPl RNF103 MARS ATP5S PPP3R1 HIST2H2AA MEF2B KDELRl CUTLl XPOT
ATPAF2 MGEA6 KIAA0635 CARS FRAGl CCNG2 BCAT2 ATRX MEF2A PLXNB2
MADH5 GNS SNPH LTA APBB3 IFRDl NCORl CDW52 SLC35E2GSN SP2 20D7-FC4 POLR2C FLOTl STC2 KIAA0141 GlO CDKI l WRB SLC7A5
GSTZl IL4R WARS CHRNA5 CAMKl CDKNlB MAP4K2WIRE PXRl ALDH6A1 CAP350 CDKNlC KIFAP3 KIAA0342 hnRNPA3 P29
C20orfl8 PYCRl ZNF36 NFIX ASNS IGSF4 BMP7 SAS DRAPl DDX46 DECRl KIAA0652 ASS KIAA1025 BTG2 YF13H12 MGC2650 PPP1R15A
PEXl IB DKFZP586P0123 UQCR MAPK13PPP2R5C RASGRP3 CREG SPONl
SLITl FLJ13052 BCKDHA LAPlB C14orfl l XPC DKFZP434J154 TCF12 SPINT2 GGTl VEGF EPS15 MMP15 KIAA0339 PIPPIN BAI2 RTP801 CLN3
SLC3A2 PEXlO ARRB2 EIF3S1 CABINl TRRAP KIAA0355 KATNBl CDC25 C IGHM
GOLGIN-67 AKR7A2 LY86 ACADVL IGBPl BIRC5 DRILl TM9SF1 FOXOlA
FUCAl CEBPB PHF2 RASAl FCGRT MAP2K3KIAA1037 RASGRP2 RAB6IP1
CSNK 1G2 ASXLl BARDl CBFA2T3 NANS LKAP ABCB9 LAPTM5 PNOC ITPR3 DDB2
GLUT_DOWN Peng_at_al_2002 UMPK IFI30 RPS26 UBE2G2 SYNGR2RNU3IP2 ILF2
PSMDI l HSP A5 COG2 FKBP2 ADRMl CAD TRIP 13 KARS FUS KHSRP MI lSl DKFZP564F0522 GOLGA1PSMD3 MLP DDX18 ACAT2 LMNBl PSMD12 TOP1 ERF BMSlL FARSL PTPN6 PPP1R10SLC19A1 SRPKl TRAl VDACl ARS2 EIF5 EMP3 SFRSl GCSH C7orfl4 RABGGTB CCNDl ICSBPl ZAP MYD88 FKBP4
ABCFl AHSAl CTSC HSPEl INHBC TCPl XPOl PRPSl FASN HRMT1L2 SRRMl EIF4G1 FNBP3 ADCY3 HNRPL SFRS2 SFl FLJ12443 MLF2 DDX21
LIMK2 XBPl ME2 TNRCI l PPIF SFPQ SLC5A6 MGC2749 PRODH CHD4
SLC29A1 NOL5A PSMD8 CELSR2 BYSL PABPNl MRPL12 COPS3 METTLl MGC5508 MAP3K11 P5 KIAA0179 SSBPl HSPCl I l KPNB2 C16orf34BOPl
DNAJAl PDCD4 CYCS HSGP25L2G KIAAOl 16 SMARCCl PTDSSl CGI-48
SNRPAl DNAJBl TGFBl ALG3 SRM PIK3R2 SURF5 HSPA8 PGAMl HSA9761 ALDOA GJBl RBBP6 CLICl SACS TUBB5 DDX 19 TDG CTPS NDUFS6 CSElL MYSTl SNRPB2 RPP20 RNASEHl EWSRl CCT2 PRPF4 TXNIP ARHG BCAP31 RANGAPl XRCC5 PPP2R2A EBNA1BP2 BTK PAICS RPLP2 PPIB
ALG8 IDHl AFlQ DOK4 SF3B4 EIF2B4 Cl lorf9 RRP4 NMEl DPH2L2 C8FW AMDl HS6ST1 PHB PSMB3 SNRP70 PRDXl IMPDHl PSMA6 PA2G4 EIF2B5 MAZ EIFlA DLEUl RBPlLl PFKP NUDC HRAS LAMB3 OGFR PRKCBPl UNRIP
FLJl 1126 ATP5G3 NOLCl EEFlEl HNRPAB ZNF207 PIK3R3 NUP98 ADAM19 FLJ12671 RAB9P40 FDFTl RUVBL2SQLE PSG7 HBD MPHOSPHlO
SLC4A7 G3BP HSPCA PSMB6 PTMS GCDH POLR2C NMP200 IDH3A MORF4L2 TUBAl MTHFDl GSPTl ATP1B3 PWP2H ClQBP NOLI UBE2M RQCDl MEP50
SSB IFRD2 MRPL3 ARMET ATR STATl SLC29A2 ATP2A2 SEC61B DYRKlA
PCBPl TAPl CCNBl PSMDl AK2 ODCl GMPS ERH IDIl ZMPSTE24 VCP TIMM 17A SNRPF HNRP A2B1 PSMFl CCT6A FBL NP DHCR7
C2F TMP21 CCT5 TUBGl C10orf7 SCD UBE2N DHX9 MRPL28 TOMM40 L3MBTLPFN1 HSPCB LDHA PRDX4 DKCl HPRTl RRSl RBM14 CDC25A GRIN2A MRPS12 BZW1 SYNCRIP PSGI l YIFl CYCl RNF126 HSP A4 BAZlA CBF2
TFRC KPNA2 MMP15 EIF4G2 CALR TBL3 VARS2 DHCR24 SARAl UMPS KIAAOl 17 SGTA LOC84549 SC4MOLLDHB NICE-4 MRPL23 YPELl GARP PRKCABP
CDC20 PSME4 EBP EIF5A DDXl NUP160 PESl MAPRE2NCL CTAGl DNAJB6 ACLY TCEBl MGC5178 IF2 DDX48 HSU15552 NMTl DHX15 TARDBP
D10S170 LEUJJP Peng_at_al_2002 ATF4 MTHFD2 CLCN6 ATF5 ISG20 APS SSR2 DAAMl PCK2 GCHFR CIRBP MARS MEF2B TNNTl MAP1LC3B CUTLl TFF3 KHSRP
XPOT ALDH2 AIMl PRKCBPl MGEA6 MIDORI HDAC5 C22orfl CARS BMPl
LOC51035 CδorfBO PLXNB2 APOBEC3G ERCC2 APBB3 GBFl NCORl UNCI 19
ITGB3BP BCL7A SUIl INS GCDH SIATl NFE2L1 101F6 KIAA0889
GlO RAB3GAP WARS CAMKl HIST1H2BE PHGDH hnRNPA3 A2LP FCER2 IGHG3 ANKRD15 PYCRl MT2A LRMP ASNS BNIP3L CKB BMP7
MUC3A POU2F3 RWl HMGAl KIAA0922 DDX46 DECRl AARS LCK IDH2 BTG2 RERE ASS CLIC4 SlOOAl I PSPH HAXl MGC2650 UBE2N CD6
PPP2R5C RASGRP3 SPAG9 PDCD4 SHOC2 IRF2 MTXl PSAP BACHl
SLC43A1 SWAP70 PCBP3 SARS SLC3A2 TNFRSF7 SIAT4C MAG VPS39
MGST2 IGHM PRELP SLC1A5 PSCDl SLC1A4 KIF2C DRILl PRKCABP CEBPB PDE6D TXNIP SURFl BMIl YARS SLC6A11 CSNK1G2 CPNE5 CD22
GPLDl LAPTM5 CDKNlA PNOC
LEU_DOWN Peng_at_al_2002 SF3B4 DHRSl PM5 PSMD14 GLO1 EIF2B4 Cl lor©
HUMGT198A AMDl DOC-IR ETFl PSMDI l HSP A5 FKBP2 ADRMl CAD RBPlLl TRIP13 UNG DKFZP564F0522 KIAA0601 KIAA0150 PSMD3 ACAT2 OGFR MCM4 FDPS TOPl EMD FARSL PTPN6 NUP98 ILF3 PIK3R3 TRAl POLG
SQLE VDACl HBD EIF5 EMP3 NXFl TNFRSFlA HSPCA PAPOLA WDRl
PTMS NME2 PSMD2 GCDH DNCLl KIAA0152 KIAA0290 FKBP4 TUBAl
MTHFDl AHSAl GSPTl CTSC HSPEl TCPl NOLI UBC C0PB2 VRKl
BST2 SSB FASN CCNA2 MRPL3 PSMB7 HRMT1L2 ARMET EIF4G1 FNBP3 PTBPl FLJ10737 SFRS2 SEC61B DYRKlA FLJ12443 CCNBl TKl
MLF2 NUTF2 DDX21 PSMDl LIMK2 NBLl ME2 PFKM ERH IDIl PGKl TIMM17A SLC29A1 GGA2 NOL5A PSMFl BYSL CCT6A NP MRPL12
ERP70 BACH MGC5508 CCT5 DHX9 UBE2N SCD KIAA0179 MRPL28 P5
TOMM40 HSPCB HSPCl I l LDHA DKFZp434K1815 DNAJAl HPRTl PDCD4 RBM14 MRPS12 CYC1 SPINT2 CYCS E2-EPF HSPA4 RNF126 EI24 CBF2 TFRC
KPNA2 MMP15 SNRPAl TCFL4 RASSF2 TGFBl SRM EIF4G2 TEBP CHCl CALR HSPA8 DHCR24 PGAMl UMPS KIAAOl 17 ALDOA CCT4 TUBB5 XPO6 LDHB
NICE-4 TDG CSElL GARP TRIP15 CDC20 PSME4 CCT2 EBP DDXl KIAA0007 XRCC5 MAP2K3NCL PSMA5 DNAJB6 POLRMT PPIB ALG8 TCEBl KIAAl 055 NMTl AFlQ PSMA7 GART BRD2 STK6
GLUCOSEJJP Peng_at_al_2002 POU2F2 DRAPl UNC119 MS4A1 COROlA AARS IDH2
GM2A CLCN6 ATF5 ADA MGST2 TCF20 24432 IGHM CROC4 SC4MOLPRB4 FLJ22531 FKBP2 PCK2 TOMM40 WARS OCLN URKLl CEBPB MS4A2
GPX6 EMSl MYB AF038169 MAP2K3ACTA1 KIAA0685 CARS BCAT2 PYCRl PLOD ASNS MFNG GART LTBR HNRPDL
GLUCOSE_DOWN Peng_at_al_2002 DKK4 HEAB FZRl EIF2B4 ELMOl ATP5J PHB
ILK SLA CALMl SSTR5 PDAP2 NMU UCHLl DAPK2 KIAA1041 AGL
RAPlA TNNTl FUS SF3A3 HLF ARPC5 KIAA0150 PRKCBPl ADCYAPl
TERF2 BMPl TEGT MSH2 SCN4A NUP98 ID2 POLG ITGB7 NAPlLl MYCN CCNGl CAPZAl G3BP KIAA0284 SFRSl MRPSl 8B ELL RABlA EIF3S3
GC20 PPP2R5A PTGER3 GCDH MAP4 DPYSL2 SMC4L1 WBSCRl ARTN
RAB2 HIPlR CD47 ASFlA TRAF5 DVL3 ADNP RAB9A ZFY CDC2 AAMP SFRS2 ATP2A2 ARF4 DYRKlA ERALl GTF2A2 VNN2 RBl RRBPl NFYB
H2AV DKFZp434I1916 POGZ IFI16 DKFZP547E1010 USP33 FUBPl EHDl HSRNAFEV MAD2L1 ESPLl GABARAP TIMM17A SH2B GJB5 MGC8721 ABO
ECE2 UBE2N SSBPl FOLRl DNAJAl BCL2 PDCD4 BFSP2 RNF6 PURB PAPSSl BAZlA MKI67 ClorfS ACKl MICB CREM COMT SIAT4C DEK USP12 SLC25A5 KIAA1093 MTVRl HTRlB EDG4 ATP6V0B CCT4 CD86 RAB31 E2F4
TUBB5 WEEl MAGEDl RANBP2 ARHGEF6 BPAGl PICALM PRKCABP GORASP2 RBBP4 SMC5 Ll TXNIP E2F1 KIFI l XRCC5 HNRPR PSMA5 SEC24C
DNAJB6 RPA3 CDC7 GPR3 RPLP2 RAB5A MYEF2 SFN ZFR SLC12A4 AFlQ GMPR FOSL2 OIP5 STK6
BRCA_UP Welcsh_et_al_2002RDX VAMP3 TITFl ID4 STCl IL16 CITED2 CLTB
SERPINBl COP9 SEC23 A PPPlRlA WRB MAP2K1 FSTLl TSNAX NFYC ZNF138 KIF2 PBP ENPP2 KCNKl HlFO ZNF148 CALDl P2RX1 GALNT3 HTATIP
APP JAKl STATl LAMA3 CCNG2 MGAT2 IDHl RRM2 ADDl LIMSl LIPA SEPPl EXTL2 TFPI2
BRCA_DOWN Welcsh_et_al_2002RXRA NDRGl BOPl GCN5L2 NUP214 CHD4 SKIV2L EIF4G1 HSFl CCNDl SLC19A1 Cl lorfB MYC FRASOR_ER_UP Frasor_et_al_2004 GREBl EGR3 EPB41L3AP1G1 IGFBP4 RAB31 SLC22A5
ADCY9 AREG TOP2A MYBLl PEGlO CXCLl 2 CDC6 CA12 GLRB PDZKl SLC39A6 SPUVE CALCR PTGES RASGRPl SDC2 MAPT Cl lorfS TFFl SIAH2 WISP2
RET FOS NRIPl RFC4 FRASOR_ER_DOWN Frasor_et_al_2004 BIK STCl KIAA0922 TGFB2 LlCAM IFI30 INHBB ARNT2 LAMBl KRTHBl ASB9 CD24 STXBPl BLNK EFNAl MYOlB CLU
HIST2H2AA COPEB MB KYNU TM4SF1 APM2 GNE SELENBPl TGFB3
HIST2H2BE BCASl ABCC5 NELL2 CBX6 GNS BMP4 RTP801 ENCl D2S448
RAPlGAl MXD4 ANXA3 EPOR PVALB DBNl PIB5PA LHFPL2 ECHl MADH3
RAI3 IER3 IRF6 ERBB2 FM05 SNK ARHE CTSL TRG@ SLIT2 FOLHl DUSPl KRT7 NDRGl ALDH4A1 DUSP4 MMD PPP1R3C PRPSl LAMB2
ASPH NFRKB MATN2 LITAF CTSH ILlRl ABCGl LOC92912 ANDROGENJJP GENES na UAPl IDIl KRTl 9 CPD SNAP25 PHYH SORD SCD
ADRMl ELL2 INPP4B SAT UGDH MERTK TMPRSS2 KLK3 AKAP12 SMS
B4GALT1 ID2 ITGAV AZGPl B2M RBMlO DHCR24 MAF LIM ORM2
ACTNl APPBP2 DCTN3 SRP19 IQGAP2 HMGCSl ABCC4 HPGD ALDH1A3 HERC3 SEC24D FKBP5 SGK GUCY1A3 NDRGl LMANl HlFO KLK2 CAMKK2
GSR KLF4 PPAP2A ANKH TMEPAI TPD52 VAPA DNAJB9 SEPPl LIFR DBI PTPN21 SLC26A2 ANDROGEN_GENES_FROM_NETAFFX na R κOυDuHri L J_ΛC-.NIN7 / R KWWDlJDJJll A ARK.SaDu C KsYXPr1i9nAj* U1
CRISPl GPX5 AKRlBlO NR1I3 TTGGFFBBllIIll CC66oorrf Ωl0055 HHSSDDl111BE 122 SSTTSS HHSSDD33BB11 RODH-4 NCOA4 FLJ21934 RDHI l SCGB2A1 APRIN UGT2B15 AKRlDl
TMPRSS2 RNF14 SHBG UGT2B4 HSDl IBl NR3C2 ABHD2 CRSP2 CYPl 1B2
SULT2A1 NR3C1 KIAA1093 HSD3B2 SRD5A1 SULT2B1 HSDl 7B8
RDH5 PPARBP VDRIP HSDl 7B3 C20orfl4FXR2 FGF8 PARTl FKBP5 RAN ARSE AKR1C4 PPAP2A AR Clδorfl NSDl CYPI lBl TMEPAI HSDl 7B2 UGT2B17 SRD5A2 UGT2B28 CRSP6 TNRCI l
AR_ORTHOS_MAPPED_TO_U133_VIA_NETAFFX na MANlAl GJB3 ADRA2CALPL ADAM7 PTPRO ISG20 GSTMl MYOM2 ISYNAl FKBPI l MTND5 BTG3 TPMT GPX5 SC4MOLERP70 GPCl GLUL CYB561 PEMT ARAFl NUCB2 FKBP5 EBP CA4 KCNKl KIAA0251 RAMP3 RRMl KCNK7 FDPS GLDC ACE STMNl AGP AT3 CA2 AGR2 FDFTl GFRAl NCF2 INDO KLRBl ENPPl TCF7 ADCY8
AR MOUSE na MANlAl GGJJBB33 ADRA2CALPL ADAM7 PTPRO ISG20 GSTMl
MYOM2 ISYNAl FKBPI l MTND5 BTG3 TPMT GPX5 SC4MOLERP70 GPCl GLUL
CYB56! I PEMT ARAFl NUCB2 FKBP5 EBP CA4 KCNKl KIAA0251 RAMP3
RRMl KCNK7 FDPS GLDC ACE STMNl AGPAT3 CA2 AGR2 FDFTl GFRAl
NCF2 INDO KLRBl ENPPl TCF7 ADCY8
AR_MOUSE_PLUS_TESTO_FROM_NETAFFX na MANlAl GJB3 ADRA2CCYP2B6
PTPRO ISG20 ISYNAl BTG3 GPX5 TPMT ERP70 GPCl CLU CYP2A13
CYB561 ARAFl FLJ21934 RAMP3 RRMl UGT2B15 FDPS CYP3A5 GLDC
ACE AGPAT3 AGR2 UGT2B4 EAF2 FDFTl GFRAl IINNDDOO KKLLRRBBll EENNPPPPll TCF7
ALPL ADAM7 GSTMl M YOM2 CYP3A4 FKBPI l MTND5 SSCC44MMOOLI ,GGLLUULL PPEEMMTT FKBP5
NUCB2 EBP CA4 KCNKl KIAA0251 AR KCNK7 CYP3A43 STMNl
UGT2B17 CA2 CYP2A6 UGT2B28 NCF2 CYP2C9 CYP3A7 ADCY8
XINACT MERGED na ARSD ATP6AP2 CA5B DDX3X EIFlAX EIF2S3 GRPR
INEl OFDl PCTKl PIR PRKX RPS4X SMCX STS TBLlX TMSB4XUBE1
USP9X UTX ZFX
TESTIS_GENES_FROM_XHX_AND_NETAFFX na MCSP TSGAlO SCMLl WDRlO SLC6A8
HLC-8 ADAM29 WTl DNALIl FAMl 2B TCTE IL DNA JC4 BRDT GRB14 ISYNAl
CRISPl PRM2 CYLC2 CHODL RNASEl ADAM2 PTGDS MAP7 USP2 PSORSlCl TCTELl DDX3Y DDX4 TFDP2 TEX13A TSKS CXADR DDX3X CLGN AMH NUP98 SOX30 TEX14 TCPI l PPP2R1B DKFZP434P211 DKFZp434H2215 TF BAT2
BGR DMRTl HSD17B3 STK22B SPACAl TTTY2 SOX5 GAPDS GPRl 35 SPINLWl
EIFlAY FLJ36166 MNSl TSC SSX2IP COIL TEX15 TTTY15 NROBl TUBA4
ALG8 POMZP3DDX43 CTAG2 HSPAlL CRAT KCTD13 ACE2 TZFP
GNF_FEMALE_GENES na HRB2 WSBl RPS27A RPS3 PTGIS RPL36AL EFEMPl CLIC4 TMODl RPS24 TCTElL TGFBR3 SRY EIF3S6 RPL21 HTR2B NNMT IGFBPl
SFRP4 NS3TP2 FTL RPL9 RPL35A RPLl 5 RPS4X GYPC RPS6 CREB3L2
CLECSF2 IGFBP5 MITF PRGl LRPl RPL7 SLC24A3 CCL21 NAPlLl
HNRPDL DHRS8 CYR61 RPL5 RPL39 HNRPAl MFGE8 AEBPl TPM4 IGFBP4
RPL6 CDHI l RBMSl IGFBP3 SH3BP5 IFITM2 RPL34 SERPINGl RPS3A RPL26 TGM2 ISLR GASl RPLl 7 ITPRl CEBPB OGT RPS 17 TXNIP COL6A3 STOM
GBP2 RPL36A GAB2 GATA6 RPL31 THBSl ADAMTSl PROSl RPLlO CACNG2
XIST EEF1B2 LAPTM5ADAM22 COL6A1 RPL24 IFI16
GATA1_WEISS Weiss_et_al_2003 HBZ MAFG TFR2 KLFl GYPA HMBS NFE2 ANKl
MAFK HEBPl FTL HB A2 SERPINIl MAFF EPB49 MAFB HEBP2 TFRC BACHl SLCl 2A5 UROS GSTT2 HBB PPOX
HEMO_TF_LIST_JP Manually Curated EE22FF22 KLFl LHX2 PAX6 FLIl HHEX MEISl
WTl HLXl FOXD3 NFYA NOTCHl PBXl MLL HOXC6 MAFB KLF3 EGRl
GFIl HOX A5 ZNFNlAl NFIB MYC ETSl EP300 TCF3 MYB HOXD13
NFIC PAX8 MAFK GBX2 HIFlA ELFl EPASl TALI NFl GATAl KLF13 HMGB3 SPIl TFAP4 BMP4 HOXB3 CREBBP POUl Fl GATA3 STAT5A NFE2 IRFl
GATA2 RUNXl ETV6 JUN DLX4 LMO2 PRRXl HOXAlOTF AP2A SP3 CEBPA
ETS2 NFKB2 STAT3 ETV4 ZNF42 CEBPB SRF E2F1 EED BMIl HOXB8
USF2 PHCl HOXA7 MEFV HOXD3 STATl H0XA9 NFKBl NFIX PAX5 P0U2F1
CEBPE HOXB6 XBPl HOX_LIST_JP Manually Curated HOXC8 HOXA6 SCMLl CBX8 LHX2 HOXD10HHEX HOXB5
MEISl HLXl HOXDl I PBXl HOXB13 HOXA5 SCML2 HOXD9 EZHl HOXA2 HOXCI l HOXD13 SCMH1 YYl GBX2 HOXA4 PHC2 HOXCl OHOXAl I HOXCl 3 HOXAl HOXDl CBX4 HOXD12HOXB3 HOXA3 EZH2 DLX4 PRRXl RNFI lO HOXA10HOXB2 HOXD4 RINGl HOOKl HOXB7 HOXC4 JJAZl EED BMIl HOXA7 PHCl HOXD3 HOXBl ASXLl HOXB9 HOXA9 HOXB6 HUMAN_CD34_ENRICHED_TF_JP Manually Curated BTEBl ZNFl 84 NT5C TANK ATF3 RUNX2 PC4 GTF2H1 ATF2 NFYA ILF2 TFCP2 E2F3 BAZ2B GTL3 NHLHl SHOX2 FHL5 MTERF JUND PITX2 ZFP161 ZNF278 ZNF9 ZNF187 GTF2H3 GATAl SPIl ILF3 CNOT8 ATBFl ZNF268 SNAIl PAXIPlL CEBPG ZNF482 GTF2H2 ETS2
SRF BAZ2A TCF2 RRN3 TCEALl ZNF324 TCF4 GTF3A SP4 SKPlA DATFl NFKBIB TCF21 ZNF205 MYB NFIC TTFl STAT5B STAT6 ZFD25 ZNF76 HIFlA
BACHl MITF FOXF2 CIZl TFAP4 MGCl 1349 C21orf96TCF7 ZNF505 POU2F2
DEK TCEA2 NFKBIA TFDPl CNOT4 ZNF281 ZNF282 CHFR CNOT2 ZNF146 STAT3 RINGl FOXFl HEYl TCFLl HSF2 BMIl TRIMlO GTF2F1 CTCF ZNF212 NFKBl TCEAl CNOT3 POU2F1 ZFP95 ELKl RNF3 ZNFl 74 ATF4 ZNFl 65 RELA ATF5 ZNF177 ZNF200 BLZFl MAZ ZNF167 UBTF ZNF22 MYC ELF3 MEF2B ZNF232
NAB2 ID3 POU5F1 PHFl ZNF262 GTF3C4 IDl MHC2TA DRl BTF3
MEF2A NCOR2 FOXGIBNCORI MAFG ID4 JUNB NONO FOXJl MTFl VENTX2 HIVEPl ZNF175 PBX2 ZNF228 CNOT7 FOXDl CITEDl MKRNl MAFF GTF2I STATl GTF2A2 NFIX FOXE3 NFYB POU6F1 ELF4 FOXMl ZNF35 MYBL2 TFE3 MYBLl LZTFLl HSF2BP SREBFl CHUK SPIB ZNF16 SNDl TCF12 RNF6 TCF7L2 FOXCl
RNF25 RNF5 ZNF294 RELB ZNF14 BAZlB TFAM CIR CGRRFl RUNX3 FLJ12985 CITED2 RUNXl E2F5 JUN THRA MAF E2F4 ISGF3G RNF13 IKBKB ATF6 ZNF42 RNF7 FOXOIACEBPB TLE2 PBX3 E2F1 MEF2C NHLH2 TCEBl REST SKI PROLIF_GENES Manually Curated IL9 TCF8 CTNNBIPl SSRl TSHR REGL CD5
SSTR5 CDK9 GPC4 CDK5RAP3 BUB3 CTFl EML4 TBC1D8 CDC27 EGR4
CAPNSl CLK4 SYK CYR61 MXD4 CTBP2 OSMR TXN CHRM5 EMP3 USP8 CXCLlO EDG5 ADRAlA BTGl RPS27 ELN SIPAl LDOCl IL7 EMPl
PRKR MET FRK ELF5 TOBl PTCH FSCNl NPDCl TGFBlIl ENPEP MS4A2 BOPl HELLS WIT-I PRKCA TGFB3 ARHGEFl DNAJA2 IGF1 KRT16 NFl
CDC14A SNFlLK DDXI l TGFBl IL2 NDN ANP32B LRPAPl CUL5 TNFRSF8 TPX2 FGF2 RBBP6 TNFRSF5 CSElL CUL3 KIF2C PRKRA PRL PRKRIR
FGG GFER RBBP4 GPNMB FES AKRl C3 SFN SON CDKNlA PCAF
CDC2L5 DLECl IL13 FANCL MKRN2 TP53I11 CCL23 C22orfl8CD33 NMEl ICOSL HDGF CAPNl PRDXl PA2G4 RBM9 MSTlR CDC16 MYC ERBB4 MASl ILlB
BTC LGIl TIEG EDNRA IL6R ANP32C IL8RB VIPRl ERBB2 OSM WARS IL12RB1 CDKNlC MCTSl APEGl CDK5R1 CDKlO SLC29A2 ILI l TNFSF5
GCG MATK DLG3 MDK IGFlR SAS TCFL5 FGF 18 QSCN6 IL4 EMP2 EREG BTG3 EDNl SIL C10orf7 CLKl IL2RA CDKN3 BINl ETSl MXIl DKCl REGlB SNDl IFNBl NR6A1 IGFBP6 EPS15 VHL ANP32E CDKN2A
CSRP2 CGRRFl POUlFl PPBP SSTR3 RUNX3 LIF FABP6 IL15 CUL4A PDGFA CUL2 LMOl COL4A3 CD86 NPY TNFSF9 BHLHB3 CXCLl TM4SF9 FGF8 TNFSF7 CDKN2C ILl 5RA MAPRE2CDK5RAP1 VEGFC CDC7 GAS6 CBFA2T3
SESNl IRS2 TSPAN-I DCTN2 FGF6 CSFlR C6orfl088D6A TAFl FGF7 CHEKl FGB CSF3 MNT CRIPl FLT3LG EGF CDK2 ADRA1BRPS4X PDAPl
ERF TACSTD2 EVI5 CHRM4 TNFRSFI lA SSTR4 CTBPl INSL4 IL2RG
HGS CDKN2D ARTN ADRAlD SKBl SIPAlLl KHDRBSl IL12RB2
BST2 IL8 GLP2R PTN TGFA TIEG2 PPMlD SPOCK TGFB2 FIGF SlOOAI l BAPl PYY RBBP7 IRF2 ANP32A TGFBR2 PRTN3 MDM2 EPS8 MKI67 TNFSF12 EGFR FGFRlOP FGF3 MAGOH IGFBP4 ILIA PAWR FTHl TOB2 CSFl
SCGF TTK SERPINFl PRG4 PCNA KLF4 IL3 TNFRSF9 INGl
PGF CDK4 MDM4 KNSL7 THPO NCK2 FLT3 IGF2 FGA RARRES3 IGFBP7 CXCL5 TIMPl DUSP22 CD81 IL5RA MT3 NAB2 NUDC FGF5 APRIN VIP TNFSF4 HDGFRP3 LAMAl COLl 8Al ADAMTS8 LRPl CD 160 ILlO NAPlLl BCL6 FZD3 GRPR GABl TM4SF4 NME2 ZFP36L2RFP FLTl
AREG PMP22 GSPTl RAFl CDKNlB MAPlA MAD NOLI IL5 IFRD2
S100A6 TNFRSF17 GNRHl APPL PTK2B DHPS ADRA2A PTHLH CD28
DTR PRDM4 CD3E VEGFB PDGFRAl -Dec BTG2 PSPH GML FABP7 TPD52L2 NDP SSTR2 IL12B KITLG BCL2 TM4SF8 CULl GRN CDC25B HOXClO IFITMl UMOD VEGF CMKORl MLLT7 BAIl TALI AIFl RARRESl MTCPl
FABP3 EVI2A JAG2 CDKN2B LAMP3 HTRlA SlOOB FGF9 TNFSF8 CHRNAlO
MAPRE1 LY86 MIA SKP2 PDGFB CD164 UBE2V2 SHCl GASl MPL CIAOl INSIGl PLG DRIM SIRPB2 DAB2 TSPAN-2 PRDX2 ILl 8 E4F1 ADAM' PTEN DOWNREG_BY_HOXA9 Manually Curated IGF2 CD36 WSBl JUNB KRTl 8 GATA2 SFRSI l MAN2A2 SERPINB9 SBNOl CDC37 JUN TPR SDCBP RBBP6 SDC4 ARNTL DSIPI MYC FCGRT GLRX SRP72 LYN DCT HBEl BMIl CLCN7 VHL OSBPL8 FXRl CISH DNCLI2
UPREG_BY__HOXA9 Manually Curated ACHYLl ADD3 ALDHlAl ARHGAPl IA ARL3
ARPC5 CALBl CDK7 CTH CUGBPl DHX8 ETS2 GNGlO GTPBPl HMGN2 HNRPU INPPLl MAFG MAN2A2 MYB NLK OSBPL9 PCMTl PHOX2APKNOX1 RAB31 RAPlB RNF103 RPL27A SFRSI l STl 3 TDE2 VIM YESl PIMl
KRAS_TOP100_CONTROL Cordero_et_al_2005 TNFRSFlOD FOSLl H3F3B LBR INHBB
FLJ20241 PARD6B BENE LRP8 BYSL TPSDl CRISPl WNT2 CXCL5 HMGA2
GPDl PPP1R3A CHITl PTMA MRPS 12 RNF6 RRM2 ETV5 UTY DKKl
TCFL4 SSPPRREEDD22 FFLLJJ220011330I 0 POLR3K ATP6V1B2 CXorfl EIF5 TLOCl EPHB3
IGF2AS MGC4606 HH22AAFFYY ARL7 SEMA6BSSX2 CTSL CEACAM6 SSRPl
CALU PHLDAl UPPl BBEEXXll PDZK2 PDE4C SKBl DUSP4 KRAS2 RAB40C EPB42
HAT EBNA1BP2 EENNTTPPDDi6 APP TEPl PARD6ASLC9A3R2 ALDH3A1
IRS2 RGS2 ODCl FF22RRLL11
KRAS TOPlOO KNOCKDOWN CCoorrddeerroo_et_al_2005 ADCY7 TGFB2 TIMP3 MUC3B C8orf4
ACVR1BSOX4 EVL SSPPAARRCC DICERl ULKl MAP3K8GPR56 TUFTl CCL2 COL4A2
IGFBP7 HGD MYL9 CCGGII--I1 K 16 SERPINEl CIS MGEA5 EPHB2 INPP4B HSPBl
GABARAPLl CALDl DDKKFFZZJp*434P162 WASPIP TGFBI DKK3 DFNA5 TNS NALPl
CMKORl BMPl SSEERRPPIINNE2 HSPG2 WISP2 TAGLN ADAM19 TPMl
MSC ITGAV LAMP2 SSTT55 COLlAl SNAIl PLEKHCl CHST3 CLDN4 DNAJB2
BHLHB2JUNB PDXK AATTPP22BB44 JUN IGFBP3 COL7A1 SLC22A5 P4HA2 GLIPRl
COL5A1 SGK COL4A1 RSUl NPTXl ECEl PGLS CDH4 JAKl KIAA0992
TMEPAI GADD45B FLRT2 MATN2 SLC16A4 LBH NCK2 IGSF4 NCF2
ARK5 SPOCK
RAR UP Manually Curated MXD4 SIAT4C ANXA6 CASPl DGATl DCN SNXlO NR2F1 NETl
GSTA4 DHRS3 OGN CTSB SLC12A2 ABCAl SSRl LBP MSLN HS3ST1 CP
CASP3 RNASEl COL4A5 AGT ENPP2 MARCKS C3 IVD VEGFC RBl
HSDI lBl FDFTl NRIPl DIO2 LAMP2
ADULT LIVER vs FETAL LIVER GNF2 Manually Curated RODH CYP4A11 ASL ABCC3
IGFALS HLA-DQBl C6orfl08 CYP2B6 CYP2E C8G APCS RARRES2
SIGIRR NRTN WARP GPDl CD81 PTGDS DKFZP586B1621 RODH-4 NNMT ACYl
APOC4 IFITMl IGFl PKLR SLC25A10 SLC22A1 G1P2 ClR HAMP
PCKl HSDI lBl GPR30 DCPS AZGPl ABHD2 CES2 COMT CLPP
DKFZp451J0118 HPD CESl NDUFA7RAB26 SHMT2 CYP27A1 STAP2 ΓΠH4
CD151 FLJ13798 CD14 NKG7 GSTMl ENDOG SLC27A5 HGFAC PPPlRlA
SDS CYP1A2 HLA-DQAl GSTZl M MYYHH77IB KIAAl 847 GSTM2 FLJl 0847
LGALSl MGC10334 ECHSl DEXI AAQQPP99 CYP2C8 ADHlC CYP2A6 UQCRCl MUCDHL
CYP2C9 IGLC2 TXNRD2
FETAL LIVER HS ENRICHED TF JP MMaannuuaallllyy CCuurraatteedd HKR3 EGR3 RBXl ZNF238 NCO A3
HHEX MLL ILF2 EGRl NNMMII SSMMAARRCCDl TFE3 IFI35 GFIl UBTF
ETSl DBP MYC HLF HHPP11--BBPP7744 SPIB SMClLl HMGBl PHC2 RNF14
ELFl SPOP ETV5 SOX13 MMEEFF22AA SSPPIIll PHTFl BAZlB H2AFY2 SIRT2 STAT5A
ID4 GTF2IRD1 HISTl H4A MMYYSSTT33 GATA2 TCERGl FOSB RUNXl TGIF
ELK3 HMGN2 ZNF282 BRD4 PROXl EEVVIIll HDACl PMFl ELK4 NR2C2 DSIPI
RNF4 MED6 RNF7 RRFFXXAANNEK . FFOOXXOOllASRF NRFl SOX15 MEF2C H2AFZ
TCFLl ZFP64 SPlOO MMDDFFII HHTTAATTIIPP DDNNMMTT:3B NSDl HCNGP DNMT3A
DDIT3 NFKBl PQBPl FFOOSS ZZNNFF443355 NNRR11HH33
CBF LEUKEMIA DOWNING AML Manually Curated MMNNll BAALC MANlAl ADCY7 PGDS
NCALD " "CACNA2D2 PTGER2 TPKl AABBRR SPARC TRIO ROBOl PURA ISG20
DUSP2 CYLN2 WFDCl RCBTBl RASA4 TTRRHH IL5RA PIK4CA TRIM8 EGLNl CBFB
WASPIP SYNGRl MKNK2 MHC2TA HHIIFFllAA CAVl CLECSF5 ADARB 1DUSP6
CBFA2T1 CRIP2 DDHHRRSS88 CCll IIoorrff2211 BBLLVVRR^A CDW52 JUNB HLA-DPAl HLA-DPBl
GALNT14 ITGB4 CCDD5588 AATTPP22BB44 NNAARRFFLL HOMER2 TBXA2RPRAME POU4F1
OGGl EGFL7 DISCI SSIIPPAAllLLll MMGGCC33222222 PMAIPl PTGIR HYAL2 IL15RA MYHI l
DEXI DNMT3B SSLLCC2255AA11 i VVAAMMPP;5 BAIAP3 HLA-DMB CD34
DKFZP434H132 PGMl CCCCNNDD33 TTPPSSBB22 WWBBSSCCIR5
1 2-Dichloroethane degradation 11_ 22--DDiicchh lloorrooeetthhaannee ddeeggrraaddiation ALDH2 ALDH3A2 ALDH1A2 ALDHlBl ALDHlAl
ACE-Inhibitor_pathway_PharmGKB ACE-Inhibitor_pathway_PharmGKB AGT AGTRl NOS3 BDKRB2KNG1 REN AGTR2 ACE
ATP synthesis ATP synthesis ATP6V1C2 ATP6V1B1 ATP6V0C ATP6V0A1
ATP5O ATP6V0B ATP6V0E ATP6V1B2 ATP6V1F ATP6V1A
ATP6V1C1 ATP6AP1 ATP6V1E1 ATP6V1G1 ATP6V1D ATP6V0D1
ATP6V1G2 ATP5E ATP6V0A4 ATP6V1H ATP6V1G3
Acetylcholine_Synthesis Acetylcholine Synthesis PDHAl PCYTlA CHKA ACHE SLC 18 A3
PEMT PDHA2 CHAT MAP3K15 ATP6V1C1 ATP6V0A1 ATP6V1B1 ATP6AP1 ATP6V1E1 ATP6V1G1 ATP6V1D ATP6V0D1 ATP6V0E
ATP6V1G2 ATP5O ATP5E ATP6V0A4 ATP6V1H ATP6V1G3 ATP6V0C
Alanine and aspartate metabolism Alanine and aspartate metabolism GOTl GAD2 NARS
GOT2 AARS DARS ADSL PC ASL ASNS GADl CRAT ASPA ABAT
GPT ASS DDO ADSS AGXT2 ATP6V1C1 ATP6V1G3 ATP6V0E
ATP6V1G1 ATP6V0D1 ATP6V0C Alkaloid biosynthesis I Alkaloid biosynthesis I TAT TYR GOTl GOT2 ABPl
AOC3 DDC AOC2 ESD CESl ABAT CRAT ADSL GAD2 ADSS DDO
AGXT2 ASNS DARS ATP6V1C1 ATP6V1G3 ATP6V0E ATP6V1G1
ATP6V0D1 ATP6V0C Alkaloid biosynthesis II Alkaloid biosynthesis II ABPl AOC3 A0C2 ESD CESl
TAT GOTl DDC ABAT CRAT ADSL GAD2 ADSS DDO AGXT2 ASNS
DARS ATP6V1C1 ATP6V1G3 ATP6V0E ATP6V1G1 ATP6V0D1
ATP6V0C Aminoacyl-tRNA biosynthesis Aminoacyl-tRNA biosynthesis WARS2 CARS NARS
KARS WARS SARS EPRS AARS TARS RARS MARS DARS HARS LARS2 IARS GARS HARSL YARS QARS
Aminophosphonate metabolism Aminophosphonate metabolism PCYTlA WARS SARS
KARS EPRS AARS TARS RARS MARS DARS HARS CARS LARS2 IARS GARS HARSL YARS QARS WARS2
Aminosugars metabolism Aminosugars metabolism CYB5R3 HEXA GFPTl HKl HEXB
HK2 GNE HK3 RENBP PGM3 GCK CMAS IARS GARS HARSL YARS CARS MARS QARS WARS2 SARS RARS TARS KARS DARS LARS2
Androgen and estrogen metabolism Androgen and estrogen metabolism CYPI lBl STS
HSDl 1B2 HSD3B1 UGT1A9 SRD5A1 HSD17B2 HSDI lBl ARSE UGT1A6
SULT2A1 HSD3B2 UGT2B4 ARSD SRD5A2 HSD17B3 AKRlDl UGTlAl UGT2B15
UGT1A3 HSD17B8 CYPl 1B2 SULTlEl UGT1A8
Apoptosis Apoptosis IRF6 COPl BCL2L11 CASP8 PRFl TP73
BCL2L2 BIRC5 IRF2 CRADD BCL2L1 TNFRSFlOB SFRS2IP TRADD BAD MCLl
JUN NFKBIA TP53 DAXX NR3C1 BIRC2 MYC IRFl FADD IRF3 TNFSFlO
CASP3 MAP2K4DFFA TNFRSFlB BCL2 BAKl NFKBIE CASP9 PTPN13 TRAF2
BID IKBKE IRF4 FAS MAPKIOAPAFI CD40 MAP3K14 MDM2 CASPlO
IRF5 TRAF6 TRAFl BCL2A1 NGFR CASPl BIRC4 DFFB NGFB HRK LTA
TNF CASP7 TNFRSFlA CD40LG CASP2 TRAF3 IRF7 BAX NTRKl PARPl
CYCS NFKBl CASP4 IKBKB CHUK CASP6 RELA IKBKG RIPKl GZMB BIRC3
TNFRSF25 FASLG NFKBIB TNFRSF21 MAP3K1 PLEKHG5 TFG HELLS
BOK BNIP3L Apoptosis_GenMAPP Apoptosis_GenMAPP CASP8 PRFl BCL2L1 TRADD MCLl
JUN NFKBIA TP53 BIRC2 MYC FADD TNFSFlO CASP3 MAP2K4 TNFRSF IB BCL2 BAKl CASP9 TRAF2 BID FAS MAPKIOAPAFI MAP3K14 MDM2
TRAFl BIRC4 TNF CASP7 TNFRSFlA CASP2 BAX PARPl CYCS NFKBl
CASP6 RELA IKBKG RIPKl GZMB BIRC3 FASLG MAP3K1 BAD SFRS2IP CHUK
CRADD CASPl BIRC5 TNFRSFlOB CASPlO TNFRSF25 IKBKB NR3C1 CASP4
NFKBIB IKBKE TNFRSF21 CD40 DAXX PLEKHG5 IRF4 TFG HELLS TP73 BOK BNIP3L TRAF3 BCL2L11 DFFA TRAF6 IRF5 IRF2 PTPN13
ApoptosisJCEGG ApoptosisJCEGG COPl CASP8 BCL2L2 CRADD BCL2L1 SFRS2IP TRADD
BAD MCLl NFKBIA DAXX NR3C1 FADD CASP3 DFFA TNFRSFlB BCL2
CASP9 PTPN13 TRAF2 IKBKE FAS APAFl CD40 CASPlO TRAF6 TRAFl BCL2A1
NGFR CASPl DFFB NGFB HRK LTA TNF CASP7 TNFRSFlA CD40LG
CASP2 TRAF3 BAX NTRKl CYCS NFKBl CASP4 CASP6 RIPKl FASLG TFG
BOK TNFRSF25 TP53 BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1
PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPKlO
IRF5 MYC IRF2 IKBKG Arginine and proline metabolism Arginine and proline metabolism GAMT NOSl MAOB P4HA1 KIAA0377 P4HB GOTl GOT2 ODCl CKB GLUDl AMDl RARS
ALDH2 OAT SMS ALDH3A2 PYCRl CKMTlB SAT ABPl ALDH4A1
ARG2 MAOA ASL CKM AOC3 CPSl CKMT2 NOS3 ARGl DAO ALDH1A2
AOC2 ASS OTC ALDHlBl NOS2A GLUD2 ALDHlAl AGMAT CATSPER2
CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS
BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPNl 3 TNFRSF25 TP53
FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4
HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2
IKBKG Ascorbate and aldarate metabolism Ascorbate and aldarate metabolism ALDH2 ALDH3A2
ALDH 1A2 ALDHlBl ALDHlAl P4HB GOT2 ODCl CKB GLUDl AMDl RARS OAT SMS PYCRl CKMTlB SAT ABPl ALDH4A1
ARG2 MAOB MAOA ASL CKM AOC3 CPSl CKMT2 GAMT NOS3 ARGl DAO A0C2 ASS OTC NOSl P4HA1 GOTl N0S2A GLUD2 AGMAT CATSPER2 CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS
BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53
FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4
HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2
IKBKG Benzoate degradation via CoA ligation Benzoate degradation via CoA ligation ACATl SDS ECHS 1
GCDH EHHADH ACYPl ACYP2 HADHA AMDl RARS ALDH2 OAT SMS
ALDH3A2 PYCRl CKMTlB SAT ABPl ALDH4A1 ARG2 MAOB
MAOA ASL CKM A0C3 CPSl CKMT2 GAMT N0S3 ARGl DAO ALDH1A2 A0C2 ASS OTC NOSl P4HA1 GOTl ALDHlBl NOS2A GLUD2 ALDHlAl AGMAT GLUDl CATSPER2 CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1
CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl
MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Benzoate degradation via hydroxylation Benzoate degradation via hydroxylation HADHB
ACAA2 ACAAl MYO5B ACYPl ACATl SDS ACYP2 GCDH HADHA AMDl RARS ALDH2 OAT SMS ALDH3A2 PYCRl CKMTlB SAT ABPl ALDH4A1
ARG2 MAOB MAOA ASL CKM A0C3 CPSl CKMT2 GAMT NOS3 ARGl DAO ALDH1A2 AOC2 ASS OTC NOSl P4HA1 GOTl ALDHlBl
NOS2A GLUD2 ALDHlAl AGMAT GLUDl CATSPER2 CASPl CASP6 APAFl
NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L
BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Bile acid biosynthesis Bile acid biosynthesis CEL HADHB ALDH2 ACAA2 ACAAl
ALDH3A2 CYP27A1 SRD5A1 ADHlC BAAT SRD5A2 ALDH1A2 AKRlDl
CYP7A1 ADH6 ADHlA ADHlB ALDHlBl ADH7 ALDHlAl ADH4 ADHFEl MY05B A0C3 CPSl CKMT2 GAMT NOS3 ARGl DAO AOC2 ASS OTC
NOSl P4HA1 GOTl NOS2A GLUD2 SAT ALDH4A1 MAOA AGMAT GLUDl
CATSPER2 RARS MAOB CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1
CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl
MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3
MAPKl 0IRF5 MYC IRF2 IKBKG
Biogenic_Amine_Synthesis Biogenic_Amine_Synthesis TPHl GAD2 DXYS 155E MAOA
GADl DDC ACHE PAH DBH PNMT HDC SLCl 8 A3 AANAT TH COMT ARVCF CHAT LOC138948 CPSl CKMT2 GAMT NOS3 ARGl DAO
ALDH1A2 A0C2 ASS OTC NOSl P4HA1 GOTl ALDHlBl N0S2A
GLUD2 ALDH3A2 SAT ALDH4A1 ALDHlAl AGMAT GLUDl CATSPER2
RARS MAOB CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25
TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5
IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC
IRF2 IKBKG Biosynthesis of steroids Biosynthesis of steroids SQLE FDPS LSS MVD NQO2 MVK IDIl FDFTl SC5DL ZNF646 VKORCl CHAT DXYS155E TPHl
LOC138948 DDC GAD2 PAH CPSl CKMT2 GAMT N0S3 ARGl DAO
ALDH1A2 AOC2 ASS OTC NOSl P4HA1 GOTl ALDHlBl NOS2A
GLUD2 ALDH3A2 SAT ALDH4A1 ALDHlAl MAOA AGMAT GLUDl
CATSPER2 RARS MAOB CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA
CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl
MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3
MAPKl 0IRF5 MYC IRF2 IKBKG Biotin metabolism Biotin metabolism BTD HLCS IDIl FDFTl SQLE LSS SC5DL
ZNF646 MVK FDPS VKORCl CHAT DXYS155E TPHl LOC138948 DDC GAD2 PAH CPSl CKMT2 GAMT NOS3 ARGl DAO ALDH1A2
AOC2 ASS OTC NOSl P4HA1 GOTl ALDHlBl NOS2A GLUD2 ALDH3A2
SAT ALDH4A1 ALDHlAl MAOA AGMAT GLUDl CATSPER2 RARS
MAOB CASPl CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6
CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25
TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5
IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC
IRF2 IKBKG Blood group glycolipid biosynthesis-lactoseries Blood group glycolipid biosynthesis-lactoseries ST3GAL3
FUT6 FUTl FUT2 FUT5 FUT3 ABO IDIl FDFTl MVK CHAT DXYS155E
TPHl LOC138948 DDC GAD2 PAH CPSl CKMT2 GAMT NOS3 ARGl
DAO ALDH1A2 A0C2 ASS OTC NOSl P4HA1 GOTl ALDHlBl
NOS2A GLUD2 ALDH3A2 SAT ALDH4A1 ALDHlAl MAOA AGMAT GLUDl CATSPER2 RARS MAOB CASPl CASP6 APAFl NR3C1 BAX CASPlO
BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3
DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA
PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl
MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Blood group glycolipid biosynthesis-neolactoseries Blood group glycolipid biosynthesis-neolactoseries
ST8SIA1 FUTl FUT2 GCNT2 ABO B3GNT1 FUT6 FUT3 ST3GAL3 IDIl
FDFTl MVK CHAT DXYS155E TPHl LOC138948 DDC GAD2 PAH
CPSl CKMT2 GAMT NOS3 ARGl DAO ALDH 1A2 AOC2 ASS OTC NOSl P4HA1 GOTl ALDHlBl NOS2A GLUD2 ALDH3A2 SAT ALDH4A1
ALDHlAl MAOA AGMAT GLUDl CATSPER2 RARS MAOB CASPl CASP6
APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS
DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD
TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4 HELLS TP73
BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Blood_Clotting_Cascade Blood_Clotting_Cascade FI l SERPINEl PLAT VWF
F8A1 SERPINB2 F5 FGB SERPINF2 PLAU FlO FGA F2 F8
F12 F9 F7 F13B PLG FGG DDC GAD2 PAH CPSl CKMT2 GAMT NOS3 ARGl DAO ALDH1A2 AOC2 ASS OTC NOSl P4HA1
GOTl ALDHlBl N0S2A GLUD2 ALDH3A2 SAT ALDH4A1 ALDHlAl
MAOA AGMAT GLUDl CATSPER2 RARS MAOB CASPl CASP6 APAFl NR3C1
BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG
BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2 NFKBIB
TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L BCL2L11
BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Butanoate metabolism Butanoate metabolism ACATl SDS PDHAl GAD2 BDH
ECHSl ALDH2 ALDH3A2 ACADS HMGCL OXCTl ALDH5A1 EHHADH GADl ABAT ALDH 1A2 HADHA PDHB ALDHlBl ALDHlAl PDH A2
ACSMl AACS MAP3K15 NOS2A GLUD2 SAT ALDH4A1 MAOA CPSl
AGMAT NOS3 GLUDl CATSPER2 RARS NOSl MAOB CASPl CASP6 APAFl
NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX
TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2 BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG BID MDM2
NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4 HELLS TP73 BNIP3L
BCL2L1 1 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
C21 -Steroid hormone metabolism C21 -Steroid hormone metabolism CYP 11 B 1 CYP 17A 1
HSDl 1B2 CYPI lAl HSD3B1 HSDI lBl HSD3B2 AKRlDl CYP21A2 CYPl 1B2 OXCTl ALDH5A1 EHHADH GADl ACATl SDS ABAT
GAD2 ALDH1A2 HADHA PDHB ALDHlBl ALDH3A2 BDH ALDHlAl
PDHA2 ACSMl AACS MAP3K15 PDHAl NOS2A GLUD2 SAT ALDH4A1
MAOA CPSl AGMAT N0S3 GLUDl CATSPER2 RARS NOSl MAOB CASPl
CASP6 APAFl NR3C1 BAX CASPlO BCL2L1 CASP8 CASP4 SFRS2IP IKBKE CD40 FAS DAXX TFG BOK TRAF3 DFFA CASP2 RIPKl TRAF6 CYCS BCL2
BAD TRAFl CASP3 NFKBl TNFRSFlA PTPN13 TNFRSF25 TP53 FASLG
BID MDM2 NFKBIB TNFRSF21 PRFl MAP3K1 PLEKHG5 IRF4 HELLS
TP73 BNIP3L BCL2L11 BIRC4 BIRC3 MAPK10IRF5 MYC IRF2 IKBKG
Calciurn_regulation_in_cardiac_cells Calcium_regulation_in_cardiac_cells GNB5 RGS7 RGSI l ADCY7 GNG12 RGS5 GNG4 GNG2 PRKCBl SLC8A1 CAMKl ATP1A4 LOC440698
PRKCH CHRM3 PRKCA RGS6 SLC8A3 ITPRl PRKCE GNG7 BCL2L1 RGS20 PRKCZ PLN GNBl C14orf91 PRKARlA CALM3 CALMl YWHAQ PEA15 GNB2 CALR ANXA6 YWHAH GNAI2 GNAI3 ITPR3 ATPlBl SARAl GJAl RGS2 PRKCD GNAQ ITPR2 PKIG PRKACB PRKACA GRK6 RGSl MYCBP ARRB2 PRKAR2B
RGS3 GNAI l RGS14 ATP 1B2 RGSlO RGS19 RGS4 GRK5 ADCY9 PKIA ATP2B2 GNAOl PRKAR2A GJA4 GJBl GNAZ RYRl GJB3 FXYD2 PRKDl USP5
GNB3 GJB5 ADRB2 PRKCG RYR3 CACNAlA RGS9 ADCY8 ADRB3 CACNBl
GJA 12 ATP2B3 KCNJ3 GNG5 CACNAlB GNGTl CALM2 CASQ2 ATP2A3 RYR2
ADRA1BCAMK2A CACNAlD CACNAlC ADRBl GRK4 KCNJ5 CACNAlE
YWHAB ATPl B3 ATP2A2 ADCY6 SFN ATP2B1 ADCY3 RGS 16 CACNB3CAMK2B PRKCQ CAMK4 ADRAlD KCNBl ADRAlA PRKARlB CAMK2G
ADCY2 ADCYl PLCB3 GJA5 NME7 LOC346329 CACNAlS ARRBl MGCl 1266
CASQl RGS17 GNG13 BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS18 CAMK2D ADCY5 C6orf204 C6orfl 25 RTDRl ADCY4 GJB6 CHRMl WDR42A
Caprolactam degradation Caprolactam degradation AKRlAl RGSI l ADCY7 GNG12 RGS5
GNG4 GNG2 PRKCBl SLC8A1 CAMKl ATP1A4 LOC440698 PRKCH CHRM3 PRKCA
GNB5 RGS6 SLC8A3 ITPRl PRKCE GNG7 BCL2L1 RGS20 PRKCZ PLN GNBl C14orf91 PRKARlA CALM3 CALMl YWHAQ PEA15 GNB2 CALR ANXA6 YWHAH
GNAI2 GNAI3 ITPR3 ATPlBl SARAl GJAl RGS2 PRKCD GNAQ ITPR2 PKIG
PRKACB PRKACA GRK6 RGSl MYCBP ARRB2 PRKAR2B RGS3
GNAI l RGS14 ATP 1B2 RGSlO RGS19 RGS4 GRK5 ADCY9 PKIA ATP2B2 GNAOl PRKAR2A GJA4 GJBl GNAZ RYRl GJB3 FXYD2 PRKDl USP5 GNB3
GJB5 ADRB2 PRKCG RGS7 RYR3 CACNAlA RGS9 ADCY8 ADRB3 CACNBl GJA12 ATP2B3 KCNJ3 GNG5 CACNAlB GNGTl CALM2 CASQ2 ATP2A3 RYR2 ADRA1BCAMK2A CACNAlD CACNAlC ADRBl GRK4 KCNJ5 CACNAlE
YWHAB ATP1B3 ATP2A2 ADCY6 SFN ATP2B1 ADCY3 RGS16 CACNB3CAMK2B
PRKCQ CAMK4 ADRAlD KCNBl ADRAlA PRKARlB CAMK2G
ADCY2 ADCYl PLCB3 GJA5 NME7 LOC346329 CACNAlS ARRBl MGCl 1266
CASQl RGS17 GNG13 BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGS 18 CAMK2D AADDCC\Y5 C6orf204C6orfl25 RTDRl ADCY4 GJB6 CHRMl WDR42A
Carbon fixation Carbon fixation FBP2 GOTl GOT2 PGKl TPIl ALDOA MDHl
PKM2 ALDOC MEl MMEE33 ALDOB GPT PKLR MDH2 FBPl TAF9L CALM3
CALMl YWHAQ GNBl PPEEAAl1:5 GNB2 CALR ANX A6 YWHAH GN AI2 GNAI3 ITPR3
ATPlBl SARAl GJAl PPRRKKCCZ RGS2 PRKCD GNAQ ITPR2 PKIG PRKACB
PRKACA GRK6 RRGGSSll MYCBP ARRB2 PRKAR2B ITPRl ADCY7 RGS3
GNB5 GNAI l RGS14 AATTPPI1lB2 RGSlO RGS19 RGS4 CAMKl GRK5 ADCY9 PKIA
ATP2B2 GNAOl PRKAR2A GJA4 PLN GJBl GNAZ GNG4 RYRl GJB3
FXYD2 PRKDl USP5 GNB3 PRKCH RGSI l GJB5 ADRB2 PRKCE PRKCG RGS7
RYR3 CACNAlA RGS9 BCL2L1 ADCY8 ADRB3 GNG7 PRKCA CACNBl GJA12
ATP2B3 SLC8A1 KCNJ3 GNG5 CACNAlB GNGTl CALM2 CASQ2 ATP2A3 RYR2 ADRAl BCAMK2A PRKCBl CACNAlD CACNAlC ADRBl GRK4 KCNJ5
CACNAlE YWHAB ATP1B3 RGS5 ATP2A2 ADCY6 SFN ATP2B1 ADCY3 RGS 16
CACNB3CAMK2B PRKCQ RGS20 RGS6 CAMK4 AADDRRAAll]D D KCNBl ADRAlA GNG12 PRKARlB CAMK2G ADCY2 ADCYl PPLLCCBB33 GGJJAA55 CHRM3 NME7
LOC346329 CACNAlS ARRBl MGCl 1266 CASQl RGS17 GNG13 BP75
CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNG2 CAMK2D
ADCY5 C6orf204C6orfl 25 RTDRl ADCY4 GJB6 CHRMl WDR42A SLC8A3 PRKARlA
Cell_cycle_KEGG Cell_cycle_KEGG ATM HDAC4 MAD2L1 RBL1 CDKNlA SMClLl
CDC25A TBC1D8 MADlLl EP300 SMAD4 CCND2 CDC14A CDC25C CDH1 PCNA HDACl
BUB3 MCM3 CCND3 TP53 MCM5 HDAC2 CDC25B MCM6 MCM2 ABLl PLKl
CDK4 E2F4 HDAC5 CCNB2 E2F1 CDC20 TGFBl RBl CDC2 ORC4L CCNA2
VPS16 PTTGl SKP2 E2F3 GADD45A BUBlB E2F6 CDC6 CCNH CDC45L
TFDPl ASK CDK2 CDC7 ESPLl ORC2L ORC5L CCNE2 ORClL MDM2 CHEKl
CCNAl HDAC6 CDKN2A E2F2 MPL CDC14B PTTG3 PRKDC MCM7 BUBl
GSK3B ORC3L CHEK2 MCM4 WEEl MPEGl EXOSC9 CCNEl PTTG2 CCNBl PTPRA
HDAC3 HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8
CDANl CCNB3 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ
PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A
ADC Y2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329
ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl
RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3
GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl
PRKCBl ADCY5 ITPR3 C6orf204 CACNA ID GNG7 ADRBl C6orfl 25 CALM2 ATP 1B3
RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE
PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS 16 SLC8A3 PRKARlA
ADRAlA ANXA6 SFN CACNB3RGS14 GJA4 CholesterolJBiosynthesis Cholesterol_Biosynthesis SQLE DLX6 FDPS DHCR7 LSS
CYP51A1 HMGCR MVD PMVK MVK IDIl HMGCSl FDFTl SC4MOL
NSDHL SC5DL ClOorfl lO CDK4 E2F4 CDKNlA HDAC5 SMAD4 CCNB2
E2F1 CDC20 TGFBl RBl CDC2 ORC4L MAD2L1 CCNA2 VPS16 PTTGl SKP2 E2F3 GADD45A BUBlB E2F6 CDC6 CCNH CDC45L TFDPl HDAC4 ASK
CDK2 CDC7 TBC1D8 CDC25A ESPL1 ORC2L MADlLl ORC5L CCNE2 ORClL CDC25C CDC14A RBL1 MDM2 CHEKl CCNAl HDAC6 CDKN2A E2F2 MPL CDC14B
ATM PTTG3 PRKDC MCM7 BUBl GSK3B BUB3 ORC3L CHEK2 TP53 MCM4 WEEl MPEGl EXOSC9 CCNEl EP300 PTTG2 CCNBl PTPRA MCM5 HDAC3 SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 CDANl
CCNB3 MCM6 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A
ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA
GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl
RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3
GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl
PRKCBl ADCY5 ITPR3 C6orf204 CACNA ID GNG7 ADRBl C6orfl25 CALM2 ATP 1B3
RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA
ADRAlA ANXA6 SFN CACNB3RGS14 GJA4
Chondroitin / Heparan sulfate biosynthesis Chondroitin / Heparan sulfate biosynthesis HS3ST3B1
XYLT2 B3GAT3 HS3ST1 HS3ST2 HS3ST3A1 B4GALT7 XYLTl IDIl SC4MOL
SQLE NSDHL FDFTl LSS SC5DL MVK CYP51A1 FDPS ClOorfl lO HMGCSl CDK4 E2F4 CDKNlA HDAC5 SMAD4 CCNB2 E2F1 CDC20
TGFBl RBl CDC2 ORC4L MAD2L1 CCNA2 VPS16 PTTGl SKP2 E2F3 GADD45A BUBlB E2F6 CDC6 CCNH CDC45L TFDPl HDAC4 ASK CDK2 CDC7 TBC1D8 CDC25A ESPLl ORC2L MADlLl ORC5L CCNE2 ORClL CDC25C CDC14A RBL1 MDM2 CHEKl CCNAl HDAC6 CDKN2A E2F2 MPL CDC14B ATM PTTG3 PRKDC MCM7 BUBl GSK3B BUB3 ORC3L CHEK2 TP53 MCM4 WEEl MPEGl EXOSC9
CCNEl EP300 PTTG2 CCNBl PTPRA MCM5 HDAC3 SMClLl HDAC7A ORC6L
FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 CDANl CCNB3 MCM6 SLC8A1
KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKAR IB CAMK2G
ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGS18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3 C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJA4 Circadian_Exercise Circadian_Exercise CBX3 RHOQ GENX-3414 EIF4G2 BTGl ETV6 MAP3K7IP2 HERPUDl SUMO3 DAZ AP2 GSTPl DNAJAl PPP2CB AZINl ZFR
TUBB3 GSTM3 TOBl PERl PSMA4 KLF9 SF3A3 PURA PPP1R3C CLDN5
IDIl CLOCK PIGF PER2 UGP2 GFRAl MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL NCOA4 CEBPB CRY2 G0S2 HLA-DMA ClOorfl lO
CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RBl HDAC6 CDK2 CCNE2 MDM2 MPL MCM4 TFDPl WEEl MPEGl EXOSC9
CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl
HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B
PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3
C6orf204 CACNA ID GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJ A4 Citrate cycle (TCA cycle) Citrate cycle (TCA cycle) IDHl ACO2 MDHl SDHA IDH3B
IDH3A IDH3G SDHB FH PC ACOl PCKl CS MDH2 DLD IDH2 DLSTP SUCLGl SDHAL2 TFRC KLF9 SF3A3 GENX-3414 PURA PPP1R3C
CLDN5 IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB
DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO TOBl CBX3 GSTM3 RHOQ PERl CDC 14A PRKDC CDC2 SKP2 ATM MCM7
CDKN2A ORC5L TP53 CDC14B RB1 HDAC6 CDK2 CCNE2 MDM2 MPL
MCM4 TFDPl WEEl MPEGl EX0SC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31
RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1
ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A
PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6or£204 CACNAlD
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS 14 GJ A4 Complement_Activation_Classical Complement_Activation_Classical C2 CIS DAF
ClQB C7 C5 C8A MASPl C9 C8B C4B C6 ClR C4A C3
ClQA ClQG C2F TFRC DLD MDHl IDHl KLF9 SF3A3 GENX-3414 PURA PPP1R3C CLDN5 IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl
MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA
EIF4G2 ClOorfl lO TOBl CBX3 GSTM3 RHOQ PERl CDC14A PRKDC CDC2
SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RBl HDAC6 CDK2 CCNE2 MDM2 MPL MCM4 TFDPl WEEl MPEGl EXOSC9 CCNEl EP300 PTTG2
CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001
E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l
RYR2 GJ A5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2
PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl
YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC
PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3 C6orf204 CACNAlD
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS 16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS 14 GJA4 Cyanoamino acid metabolismCyanoamino acid metabolism ATP6V0C GGTl SHMTl SHMT2
GGT2 MASPl ClR C4A C3 ClQA ClQG C2F C7 DAF TFRC
DLD MDHl IDHl KLF9 SF3A3 GENX-3414 PURA PPP1R3C CLDN5
IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO
TOBl CBX3 GSTM3 RHOQ PERl CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RBl HDAC6 CDK2 CCNE2 MDM2 MPL
MCM4 TFDPl WEEl MPEGl EXOSC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl
SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A
PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNAl D
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3 RGS 14 GJA4 Cysteine metabolism Cysteine metabolism CARS GOTl LDHA GOT2 LDHB
MPST CTH LDHC SHMTl MASPl ClR C4A C3 ClQA ClQG C2F C7
DAF TFRC DLD MDHl IDHl KLF9 SF3A3 GENX-3414 PURA PPP1R3C CLDN5 IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl
Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO
TOBl CBX3 GSTM3 RHOQ PERl CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RB1 HDAC6 CDK2 CCNE2 MDM2 MPL MCM4 TFDPl WEEl MPEGl EX0SC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl
MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31
RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNA ID
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS14 GJA4 D-Arginine and D-ornithine metabolism D-Arginine and D-ornithine metabolism DAO
GOTl LDHA GOT2 LDHB CARS MPST CTH LDHC SHMTl MASPl ClR C4A C3 ClQA ClQG C2F C7 DAF TFRC DLD MDHl IDHl
KLF9 SF3A3 GENX-3414 PURA PPP1R3C CLDN5 IDIl CLOCK PIGF
PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl Clorfl HSP A8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3
G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO TOBl CBX3 GSTM3
RHOQ PERl CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L
TP53 CDC14B RB1 HDAC6 CDK2 CCNE2 MDM2 MPL MCM4 TFDPl WEEl MPEGl EX0SC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8
GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARl B CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2
ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329
ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl
RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3
GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl
PRKCBl ADCY5 ITPR3 C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE
PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA
ADRAlA ANXA6 SFN CACNB3RGS14 GJA4
D-Glutamine and D-glutamate metabolism D-Glutamine and D-glutamate metabolism GLS2
GLUDl GLS GLUD2 ClR MASPl C4A C3 ClQA ClQG C2F C7 DAF TFRC DLD MDHl IDHl KLF9 SF3A3 GENX-3414 PURA PPP1R3C
CLDN5 IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO
TOBl CBX3 GSTM3 RHOQ PERl CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RBl HDAC6 CDK2 CCNE2 MDM2 MPL
MCM4 TFDPl WEEl MPEGl EX0SC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7 A ORC6L FLJ14001 E2F5 RPL31
RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A
PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2
CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3 C6orf204 CACNA ID GNG7 ADRBl Cόorfl 25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS 14 GJA4 DNA polymerase DNA polymerase POLA POLE POLD2 POLG POLDl POLB POLQ
GLS GLUD2 ClR MASPl C4A C3 ClQA ClQG C2F C7 DAF
TFRC DLD MDHl IDHl KLF9 SF3A3 GENX-3414 PURA PPP1R3C
CLDN5 IDIl CLOCK PIGF PER2 UGP2 ETV6 GFRAl MYF6 UCP3 NCKAPl Clorfl HSPA8 VAPA CRYl NR1D2 ARNTL MAP3K7IP2 NCOA4 AZINl CEBPB DAZAP2 CRY2 ZFR TUBB3 G0S2 HERPUDl HLA-DMA EIF4G2 ClOorfl lO
TOBl CBX3 GSTM3 RHOQ PERl CDC14A PRKDC CDC2 SKP2 ATM MCM7 CDKN2A ORC5L TP53 CDC14B RBl HDΛC6 CDK2 CCNE2 MDM2 MPL
MCM4 TFDPl WEEl MPEGl EX0SC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl MCM5 HDAC3 CDC25C SMClLl HDAC7A ORC6L FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl
SMAD4 MCM6 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQPRKAR1B CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A
PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNAlD
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS14 GJA4
DNA replication Reactome DNA replication Reactome RFC2 PRIM2A POLA POLE RPS27A
UBB NACA P0LD2 PCNA RPAl MCM3 MCM5 RP A2 MCM6 MCM2 POLD4 RFC5 ORC4L POLDl CDC6 RFC4 CDC45L RFC3 ASK CDK2 POLA2 CDC7
ORC2L ORC5L PRIMl ORClL DIAPH2 P0LE2 RFCl MCM7 UBC RP A3 CDTl ORC3L MCM4 POLD3 EPAG GMNN ORC6L MCMlO RPA4 UBA52 LOC388720 CBX3 UGP2 ETV6 IDIl Clorfl MAP3K7IP2 GSTM3 RHOQ VAPA PPP1R3C AZINl PERl PER2 ZFR CDC14A PRKDC CDC2 SKP2 ATM CDKN2A TP53 CDC14B RB1 HDAC6 CCNE2 MDM2 MPL TFDPl WEEl MPEGl EX0SC9
CCNEl EP300 PTTG2 CCNBl PTPRA BUBl HDAC3 CDC25C SMClLl HDAC7A FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4
HDAC5 CCNB3 CCNB2 MADlLl SMAD4 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNGl 2 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADC Y2 ADCYl CAMK2B PLCB3
GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7
ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3
C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJA4 Eicosanoid_Synthesis Eicosanoid Synthesis PTGS2 ALOX 15B TBXASl PLA2G2A
ALOX5AP ALOX5 PLA2G6 PTGSl DPEPl LTC4S GGTl ALOX12 ALOX 15 PTGES
PTGIS LTA4H PTGDS GGT2 IPLA2(GAMMA) RPA3 CDTl ORC3L MCM7 ORC5L UBC CDK2 MCM4 POLD3 PRIM2A POLE P0LD2 MCM5 UBB EPAG GMNN ORC6L MCMlO RPA4 UBA52 NACA RFC3 DIAPH2 MCM6 LOC388720 RPS27A CBX3 UGP2 ETV6 IDIl Clorfl MAP3K7IP2 GSTM3 RHOQ VAPA PPP1R3C
AZINl PERl PER2 ZFR CDC14A PRKDC CDC2 SKP2 ATM CDKN2A TP53 CDC14B RB1 HDAC6 CCNE2 MDM2 MPL TFDPl WEEl MPEGl EXOSC9 CCNEl EP300 PTTG2 CCNBl PTPRA BUBl HDAC3 CDC25C SMClLl HDAC7A FLJ14001 E2F5 RPL31 RIN3 MAD2L2HDAC8 GSK3B E2F2 CDANl HDAC4 HDAC5 CCNB3 CCNB2 MADlLl SMAD4 ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l
CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR
ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3
GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7
ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3
C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3RGS14 GJA4
Electron_Transport_Chain Electron_Transport_Chain SLC25A27 ATP5S NDUFAlO
NDUFS4 ATP5H NARGl ATP5J2 COX17 NDUFB6 NDUFS 1 ATP5O TATDNl COX4I1 SLC25A5 UQCRC2COX6A1 SDHA COX7C NDUFB8COX7A2L NDUFA5ATP5B COX6B1 QP-C
COX7A2NDUFS3 CD14 COX6C NDUFS5 UQCRC 1 NDUFS2 NDUFA6 SDHC SDHD NDUFABl UQCR COX7B UQCRH NDUFAl ATP5J COX5B SDHB NDUFA7SLC25A4 NDUFB7
NDUFV2NDUFS8 NDUFB3 NDUFCl COXI l NDUFS6 NDUFB5 COX5A ATP5D SURFl COX7A1 SLC25A14 ATP5C1 UQCRB COX6A2 NDUFBl ATP5I UCP3 ATP5G3 ATP5L NDUFVl
ATP5G2 CYCS UQCRFSl NDUFA9ATP5G1 UCP2 IK NDUFA2RNF113A
NDUFS7 ATP5F1 SLC25A6 ATP5A1 15E1.2 RPAl NDUFA4ATP5E NDUFC2NDUFA8 UCRC NDUFB2NDUFB4NDUFA3KBTBD4ATPIF1 POPDC2 UCP1 SDHAL2NDUFB9NDUFB10
SCOl NDUFA12 PTPMTl NDUFV3TFRC LOC257177 CDKLl SMAD4 HDAC7A
MDM2 MCM6 FLJ14001 PTPRA SMClLl MAD1L1HDAC3 ATM HDAC4 RPL31
ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNA ID
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS14 GJA4 Fatty acid biosynthesis (path 1) Fatty acid biosynthesis (path 1) ACACB ACACA FASN
MT ATP5J2 COX17 NDUFB6 NDUFS 1 ATP5O TATDNl COX4I1 SLC25A5 UQCRC2
COX6A1 SDHA C0X7C NDUFB8 COX7A2L NDUFA5ATP5B COX6B1 QP-C COX7A2
NDUFS3 CD14 C0X6C NDUFS5 UQCRC 1NDUFS2 NDUF A6 SDHC SDHD NDUFABl UQCR C0X7B UQCRH NDUFAl ATP5J C0X5B SDHB NDUFA7SLC25A4 NDUFB7 NDUFV2NDUFS8 NDUFB3 NDUFCl COXI l NDUFS6 NDUFB5 COX5 A ATP5D SURFl C0X7A1
SLC25A14 ATP5C1 UQCRB COX6A2NDUFB1 ATP5S ATP5I UCP3 ATP5G3 ATP5L
NDUFV1ATP5G2 CYCS UQCRFSl NDUFA9ATP5G1 UCP2 IK NDUFA2NDUFS4
RNFl 13A ATP5H NDUFS7 ATP5F1 SLC25A6 ATP5A1 15E1.2 RPAl NDUFA4
ATP5E NDUFAlO NDUFC2NDUFA8UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP1 SDHAL2 NDUFB9NDUFB10 SCOl NDUFA12 PTPMTl
NDUFV3TFRC SLC25A27 LOC257177 CDKLl SMAD4 HDAC7A MDM2
MCM6 FLJ14001 PTPRA SMClLl MAD ILl HDAC3 ATM HDAC4 RPL31 ORC5L
GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5
PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNAlD
GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A
CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS14 GJA4 Fatty acid biosynthesis (path 2) Fatty acid biosynthesis (path 2) ACATl SDS HADHB
ECHSl ACAA2 ACAAl EHHADH HADHA MY05B UQCRC2COX6A1 SDHA COX7C
NDUFB8COX7A2L NDUFA5ATP5B COX6B1 QP-C COX7A2NDUFS3 CD 14 COX6C
NDUFS5 UQCRC 1NDUFS2 NDUF A6 SDHC SDHD NDUFABl UQCR COX7B UQCRH
NDUFAl ATP5 J C0X5B SDHB COX4I1 NDUFA7SLC25A4 NDUFB7NDUFV2ATP5J2 NDUFSl NDUFS8 NDUFB3 NDUFCl COXI l NDUFS6 NDUFB6NDUFB5 COX5A COX17 ATP5D
SURFl COX7A1 SLC25A14 ATP5C1 UQCRB COX6A2 NDUFBl ATP5S ATP5I UCP3
ATP5G3 ATP5L NDUFV1ATP5G2 CYCS UQCRFSl NDUFA9ATP5G1 UCP2 IK
NDUFA2NDUFS4 RNF113A ATP5H NDUFS7 ATP5F1 SLC25A6 ATP5A1 15E1.2
RPAl ATP5O NDUFA4ATP5E NDUFAlO NDUFC2 NDUF A8 UCRC NDUFB2NDUFB4 NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP1 SDHAL2 NDUFB9 NDUFB 10 SCOl
NDUFA12 PTPMTl NDUFV3TFRC SLC25A27 LOC257177 CDKLl SLC25A5 SMAD4 HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MAD1L1 HDAC3
ATM HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1
CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJA4 Fatty acid metabolism Fatty acid metabolism CYP2E 1 CYP2 A6 CYP 19 A 1 CYP4A 11 ACATl CYP4B1 SDS ACOXl ACSL4 DLX6 HADHB ECHSl ALDH2 ACSL3 ACSLl
ACAA2 ACAAl ALDH3A2 CYP51A1 ACADS ACADM GCDH CPTlA CPT2
CYP2J2 EHHADH ACOX2 CYPlAl CYP3A5 CYP3A7 CYP3A4 ACADL ADHlC CYP2B6
ALDH1A2 CYP2D6 ADH6 CYP1A2 CYP2A7 ADHlA CYP2F1 CYP2C18 CYP2C8
HADHA ADHlB ALDHlBl DCI CPTlB CYP2B7P1 ADH7 CYP4F8 ALDHlAl CYP3A5P2 CYP2C9 CYP2C19 ACSL5 ADH4 ADHFEl MYO5B UCRC NDUFB2
NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl SDH AL2 NDUFC2 NDUF A2 NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl COX6A1 NDUFV3NDUFA10
ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl NDUFS8 NDUFSl ATP5S LOC257177
CDKLl SLC25A5 UQCRC2NDUFS7 NDUFB 1 SMAD4 HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MAD1L1 HDAC3 ATM HDAC4 RPL31 ORC5L GSK3B
TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA
CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6
CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH
ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75
CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3 C6orf204 CACNAlD GNG7 ADRBl
C6orfl25 CALM2 ATP 1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4
GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3RGS14
GJA4 Fatty_Acid_Degradation Fatty Acid Degradation ACSL4 ACADVL TPIl HADHB
HADHSC ACSL3 ACSLl MGC5139 ACADS ACADM LPL CPTlA SLC25A20 CPT2 ACADSB CRAT ACADL HADHA GPD2 CPTlB ACSL6 GK2 ACSL5
MYO5B CYP2D6 ADH6 CYP 1A2 ACOXl CYP2A7 ADHlA CYP2F1 CYP2C 18 CYP2C8
CYP3A4 GCDH ADHlB ALDHlBl DCI CYP2E1 CYP4B1 CYP2B7P1 ADH7
ALDH3A2 CYP4F8 CYP4A11 CYP2A6 CYP3A7 ALDHlAl CYP3A5P2
ACAAl CYP2C9 CYP2C19 CYP51A1 CYP2B6 ADH4 ADHFEl CYP 19Al CYP3A5 UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl
SDHAL2NDUFC2NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl
COX6A1 NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl
NDUFS8 NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFBl
SMAD4 HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MADlLl HDAC3 ATM HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5
RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1
CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B
PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3
C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJA4 Fatty Acid Synthesis Fatty_Acid_Synthesis ACACB PRKAA 1 PRKAB2 ACACA SCD
HADHSC ACLY PRKAGl PRKABl PC PRKAA2 SLC25A1 FASN PRKAG2
PRKAG3 MYO5B ACSL5 ACSL6 GPD2 ACADSB HADHA ACSL3 CYP2D6 ADH6 CYP1A2 ACOXl CYP2A7 ADHlA CYP2F1 CYP2C18 CYP2C8 CYP3A4 GCDH ADHlB
ALDHlBl DCI CYP2E1 CPTlB CYP4B1 CYP2B7P1 ADH7 ALDH3A2 CYP4F8 CPTlA CYP4A11 CYP2A6 CYP3A7 ALDHlAl CYP3A5P2 ACAAl
CYP2C9 CYP2C19 CYP51A1 CYP2B6 ADH4 ADHFEl CYP 19Al CYP3A5
UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl SDHAL2 NDUFC2NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl COX6A1 NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl NDUFS8
NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFB 1 SMAD4
HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MADlLl HDAC3 ATM
HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKAR IB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3
GNAl 1 RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7
ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3
C6orf204 CACNAlD GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA
ANXA6 SFN CACNB3RGS14 GJA4 Flagellar assembly Flagellar assembly ATP6V1C2 ATP6V1B1 ATP6V0C ATP6V0A1
ATP5O ATP6V0B ATP6V0E ATP6V1B2 ATP6V1F ATP6V1A
ATP6V1C1 ATP6AP1 ATP6V1E1 ATP6V1G1 ATP6V1D ATP6V0D1
ATP6V1G2 ATP5E ATP6V0A4 ATP6V1H ATP6V1G3 PRKAA2ACACA
HADHSC ACSL5 ACSL6 MYO5B GPD2 ACADSB HADHA ACSL3 CYP2D6 ADH6 CYP 1A2 ACOXl CYP2A7 ADHlA CYP2F1 CYP2C 18 CYP2C8 CYP3A4 GCDH
ADHlB ALDHlBl DCI CYP2E1 CPTlB CYP4B1 CYP2B7P1 ADH7 ALDH3A2
CYP4F8 CPTlA CYP4A11 CYP2A6 CYP3A7 ALDHlAl CYP3A5P2 ACAAl
CYP2C9 CYP2C19 CYP51A1 CYP2B6 ADH4 ADHFEl CYP 19Al CYP3A5
UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl SDHAL2 NDUFC2NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl COX6A1
NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl NDUFS8
NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFBl SMAD4
HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MADlLl HDAC3 ATM
HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR
ATP2A3 PRKAR2A PRKCA CAMK2A ADC Y2 ADCYl CAMK2B PLCB3
GNAIl RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7
ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS 17 GNG 13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGS 18 GNAQ GNG2 CAMK2D ADC Y3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3
C6orf204 CACNAlD GNG7 ADRBl C6orfl25CALM2 ATP 1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANX A6 SFN CACNB3RGS14 GJA4
Folate biosynthesis Folate biosynthesis ALPL DHFR FPGS GGH GCHl ALPP ALPI
ALPPL2 ATP6V1A ATP6V1C1 ATP6V0A1 ATP6V1B1 ATP6AP1
ATP6V1E1 ATP6V1G1 ATP6V1D ATP6V0D1 ATP6V0E ATP6V1G2
ATP5O ATP5E ATP6V0A4 ATP6V1H ATP6V1G3 ATP6V0C PRKAA2 ACACA HADHSC ACSL5 ACSL6 MYO5B GPD2 ACADSB HADHA ACSL3
CYP2D6 ADH6 CYP 1A2 ACOXl CYP2A7 ADHlA CYP2F1 CYP2C 18 CYP2C8 CYP3A4
GCDH ADHlB ALDHlBl DCI CYP2E1 CPTlB CYP4B1 CYP2B7P1 ADH7
ALDH3A2 CYP4F8 CPTlA CYP4A11 CYP2A6 CYP3A7 ALDHlAl CYP3A5P2
ACAAl CYP2C9 CYP2C19 CYP51A1 CYP2B6 ADH4 ADHFEl CYPl 9Al CYP3A5 UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl
SDHAL2NDUFC2NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl
COX6A1 NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl
NDUFS8 NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFBl
SMAD4 HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MAD ILl HDAC3 ATM HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5
RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKAR IB CAMK2G ATP2B1
CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B
PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13
CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADC Y5 ITPR3
C6orf204 CACNA ID GNG7 ADRBl C6orfl25 CALM2 ATP 1B3 RTDRl ADCY4 GJB6
CHRMl KCN J3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3RGS14 GJA4
Fructose and mannose metabolism Fructose and mannose metabolism FBP2 HKl TPIl
ALDOA PFKP AKRlBl SORD ALDOC MPI HK2 PMM2 PMMl ALDOB FPGT KHK HK3 PFKFBl FBPl PFKM GCK GMPPA GMPPB MARKl ATP6V0D1 ATP6V0C PRKAA2 ACACA HADHSC ACSL5 ACSL6 MY05B GPD2 ACADSB HADHA ACSL3 CYP2D6 ADH6 CYP1A2 ACOXl CYP2A7 ADHlA CYP2F1 CYP2C18
CYP2C8 CYP3A4 GCDH ADHlB ALDHlBl DCI CYP2E1 CPTlB CYP4B1 CYP2B7P1
ADH7 ALDH3A2 CYP4F8 CPTlA CYP4A11 CYP2A6 CYP3A7 ALDHlAl
CYP3A5P2 ACAAl CYP2C9 CYP2C19 CYP51A1 CYP2B6 ADH4 ADHFEl
CYP19A1 CYP3A5 UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl SDHAL2 NDUFC2NDUFA2NDUFB9 NDUFBlO SCOl NDUFA12
UQCR PTPMTl COX6A1 NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27
NDUFCl NDUFS8 NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7
NDUFBl SMAD4 HD AC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MADlLl
HDAC3 ATM HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNG12 BCL2L1 ATP2A2 YWHAQ PRKAR IB CAMK2G
ATP2B1 CALR ATP2A3 PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B
PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3
NME7 ATP2B2 PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS
PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB
RGS18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3
C6orf204 CACNAl D GNG7 ADRBl C6orfl25 CALM2 ATP1B3 RTDRl ADCY4 GJB6
CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH
GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3RGS14 GJA4
G13_Signaling_Pathway G13_Signaling_Pathway SH3MD2CFL1 ARHGDIB RHOA
WASL CDC42 DIAPHl ARHGEFl RACl PIK3R2 ROCKl CALM3 PFNl CALMl
IQGAPl PPPlCB SARAl PKNl MCRSl ROCK2 IQGAP2 PIK3CD MAP3K4RPS6KB1 LIMKl PIK3CA MAPKlOWAS PIP5K2AMYBPH PDIA2 ARHGDIG GNA13 CALM2 MYLl PIK3CB CIT PAK3 CFL2 RTKN RHPN2 CYP2B6 CYP4A11 CYP2C9
ACSL5 ADH4 ADHFEl ACOXl CYP19A1 HADHA ACSL3 MYO5B CYP3A5 CYP3A7
UCRC NDUFB2NDUFB4NDUFA3KBTBD4 ATPIFl NARGl POPDC2 UCP3 UCPl SDHAL2 NDUFC2NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 UQCR PTPMTl COX6A1
NDUFV3NDUFA10 ATP5G3 CYCS COX5A TFRC SLC25A27 NDUFCl NDUFS8 NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFB 1 SMAD4
HDAC7A MDM2 MCM6 FLJ14001 PTPRA SMClLl MADlLl HDAC3 ATM
HDAC4 RPL31 ORC5L GSK3B TFDPl ESPLl E2F4 SLC8A1 KCNJ5 GNB5 RGSI l GNG12 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3
PRKAR2A PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5 RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2
PRKACA PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl
YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC
PRKCZ BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGSl 8 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNA ID GNG7 ADRBl C6orfl25 ATP1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB
CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4
GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3RGS14
GJA4 Gl_to_S_cell_cycle_Reactome Gl_to_S_cell_cycle_Reactome ATM CREBLl PRIM2A RBLl CCNG2 CDKNlA CDC25A MYT1 MNATl POLE CCND2 NACA PCNA
RPAl MCM3 CCND3 TP53 MCM5 RPA2 MCM6 MCM2 CDK4 E2F4 MYC E2F1 RBl ORC4L TFDP2 E2F3 GADD45A E2F6 CCNH CDC45L TFDPl
CDKN2C CDK2 POLA2 ORC2L ORC5L CCNE2 PRIMl ORClL MDM2 CCNAl
POLE2 CDKN2A E2F2 CDKN2B CCNDl MCM7 CDKNlB CREB3 RPA3 ORC3L CDKN2D CDK7 MCM4 WEEl CREB3L1 CDKNlC
CCNEl CCNBl ORC6L FLJ14001 E2F5 GBA2 CREB3L4 CREB3L3
C20orf36NDUFA2NDUFB9NDUFB10 SCOl NDUFA12 ATPIFl UQCR KBTBD4
PTPMTl COX6A1 NDUFV3NDUFB2 NARGl NDUFAlO UCRC ATP5G3 NDUFB4CYCS
COX5A TFRC SLC25A27 NDUFCl NDUFS8 NDUFSl ATP5S LOC257177 CDKLl SLC25A5 UQCRC2NDUFS7 NDUFBl SM AD4 HDAC7A PTPRA SMClLl MADlLl
HDAC3 HDAC4 RPL31 GSK3B ESPLl SLC8A1 KCNJ5 GNB5 RGSI l CALMl GNGl 2 BCL2L1 ATP2A2 YWHAQ PRKARlB CAMK2G ATP2B1 CALR ATP2A3 PRKAR2A
PRKCA CAMK2A ADCY2 ADCYl CAMK2B PLCB3 GNAI l RYR2 GJA5
RGS6 CHRM3 CACNAlA GJB3 ADCY9 ATP2B3 NME7 ATP2B2 PRKACA
PRKCE RGSl ITPRl LOC346329 ADRB3 CACNAlS PRKDl YWHAB RGS5 PRKCH ARRBl MGCl 1266 CASQl RGS3 RGS17 GNG13 CACNAlC PRKCZ
BP75 CHRM2 CHRM5 CHRM4 GNG3 GJB2 GNB4 PKIB RGS 18 GNAQ GNG2 CAMK2D ADCY3 PKIA ATPlBl PRKCBl ADCY5 ITPR3 C6orf204 CACNAl D
GNG7 ADRBl C6orfl25 CALM2 ATP 1B3 RTDRl ADCY4 GJB6 CHRMl KCNJ3 RYR3 PRKACB CACNAlB CACNAlE PRKCG YWHAH GNBl PRKCQ WDR42A CAMK4 GRK4 RGS16 SLC8A3 PRKARlA ADRAlA ANXA6 SFN CACNB3
RGS 14 GJA4 GPCRDB_Class_A_Rhodopsin-like GPCRDB_Class_A_Rhodopsin-like BRS3 HTR6 GPR6
P2RY10 PTGFR OR8B8 HRH3 RGR PTGIR OR10A5 ADORA2A OR2H1 CMKORl
P2RY5 CCBP2 CHRM3 HTR4 CHML ORlCl ORlQl CX3CR1 BCL2L1 F2R P2RY13 GNB2L1 GALT EDNRB EDNRA PTGER4 CCRl FPRl GPR109B AGTRl MClR
ADORAl HRHl BDKRB2ADORA2B BLRl ADRA2CADRB2 ADORA3
GPRl 7 GPR4 AVPRl AP2RY2 PTAFR CCR7 GPR44 F2RL1 RHO OPRLl CNR2 DRD2 PTGER2 P2RY14 HTR2B F2RL2 ADRB3 OXTR NTSR2 GPR23 GPR161 CCR2 CCR6 CCR5 IL8RB GPR37L1 HTR2A F2RL3 LHCGR AGTR2 HTR2C NMBR NTSRl HTRlD HCRTR2NPY5R HTRlE CCR9 P2RY1 BDKRBl OPRKl TBXA2R ADRAlB
HCRTRl PTGERl GPR171 CMKLRl CXCR3 OPRDl HTR7 GRPR CNRl OPRMl
OPNlSW CCR8 OR5V1 AVPR2 MASl ADRBl DRD4 AVPR1B OR7A5 CCR3
GPR50 RRH P2RY6 SSTRl DRD5 MTNRlB MC5R GPR39 CXCR4 GPR37
ADRA2A C3AR1 ELA3A LTB4R GPR35 GPRl 8 CCKBR NPY6R GPR30 NPY2R FPRLl HTRlB PPYRl ADRAlD CCKAR GPR45 FSHR GALR2 GPR68 CCRL2
TRHR ADRAlA DRD3 LYPDl AGTRLl GPR65 P2RY11 FPRL2 SSTR2 GPR3
DRDl PTGDR LOC93164 CYSLTRl 0R7C1 0PN3 GPR85 GPR87 C5R1
CCRLl GPR75 CCRlO HRH2 CYSLTR2 GALRl GPR63 GPR77 GPRl 73 GPR27
CHRM2 ORI lAl CHRM5 HTRlA GPR24 CHRM4 GHSR HTR5A MTNRlA NMURl GPR42 GPR147 ORlFl OR12D3 MC3R HTRlF GPR83 GPR34 SUCNRl NMUR2 P2RY 12
GPR81 GPR74 GPR174 EIF4E3 GPR92 CHRMl GPRlO PHGDHLl Rgr GPR82
GALR3 GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS17 CAMK2G ATP2A2 ITPRl WDR42A CAMK2D CALMl CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 PRKARlA CACNAlD RYR2
GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GNAI l GJA4
GPCRDB_Class_A_Rhodopsin-like2 GPCRDB_Class_A_Rhodopsin-like2 GPRl 09B GPRl 61
GPR171 GPR39 GPR18 GPR45 GPR68 LYPDl GPR65 CYSLTRl GPR75 CYSLTR2
GPR42 GPR34 GPR81 PHGDHLl GPR82 P2RY13 GNB2L1 GALT F2R EDNRB EDNRA PTGER4 ADORA2A CCRl FPRl AGTRl MClR ADORAl HRHl
BDKRB2ADORA2B CX3CR1 CHML BLRl ADRA2CADRB2 ADORA3 PTGIR
GPR17 GPR4 AVPR1AP2RY2 PTAFR CCR7 GPR44 F2RL1 RHO OPRLl CNR2 DRD2 PTGER2 P2RY14 HTR2B BCL2L1 F2RL2 ADRB3 OXTR CCBP2 NTSR2 HTR6 GPR23 CCR2 CCR6 CCR5 IL8RB GPR37L1 RGR HTR2A PTGFR F2RL3 LHCGR AGTR2 HTR2C NMBR NTSRl HTRlD BRS3 HCRTR2NPY5R HTRlE CCR9
P2RY1 BDKRBl OPRKl TBXA2RHTR4 ADRAIBHCRTRI PTGERl CMKLRl CXCR3
OPRDl HTR7 GRPR CNRl OPRMl OPNlSW CCR8 OR5V1 AVPR2 MASl
ADRBl DRD4 AVPRlB OR7A5 CCR3 GPR50 RRH P2RY6 SSTRl DRD5 MTNRlB MC5R CXCR4 GPR37 ADRA2A C3AR1 ELA3A LTB4R GPR35 CCKBR NPY6R GPR30 NPY2R FPRLl HTRlB PPYRl ADRAlD CCKAR FSHR GALR2 CCRL2
TRHR ADRAlA DRD3 CMKORl AGTRLl P2RY11 FPRL2 CHRM3 SSTR2
GPR3 P2RY10 DRDl GPR6 PTGDR LOC93164 OR7C1 0R2H1 P2RY5 OPN3
GPR85 GPR87 C5R1 CCRLl HRH3 CCRlO HRH2 GALRl GPR63 GPR77 GPR173 GPR27 CHRM2 ORI lAl CHRM5 HTRlA GPR24 CHRM4 GHSR HTR5A MTNRlA NMURl GPR147 ORlFl OR12D3 MC3R HTRlF GPR83 SUCNRl NMUR2 P2RY 12 GPR74
GPR174 EIF4E3 GPR92 CHRMl GPRlO Rgr GALR3 GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 ITPRl WDR42A CAMK2D CALMl CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 PRKARlA CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS 14 GNAI l GJA4
GPCRDB_Class_B_Secretin-like GPCRDB_Class_B_Secretin-like SCTR CD97 LPHNl
VIPRl PTHRl VIPR2 GPR64 CALCRLPTHR2 LPHN2 EMRl ADCYAPlRl EMR2 GHRHR CALCR CRHR2 GIPR GLPlR CRHRl LPHN3 ELTDl GLP2R HRHl BDKRB2 ADORA2B CX3CR1 CHML BLRl ADRA2CADRB2 AD0RA3 PTGIR GPRl 7
GPR4 AVPR1AP2RY2 PTAFR CCR7 GPR44 F2RL1 RHO OPRLl CNR2 DRD2 PTGER2 P2RY14 HTR2B BCL2L1 EDNRB F2RL2 ADRB3 OXTR CCBP2 NTSR2 HTR6 GPR23 GPRl 61 CCR2 CCR6 CCR5 IL8RB GPR37L1 RGR HTR2A PTGFR
F2RL3 LHCGR AGTR2 HTR2C NMBR NTSRl HTRlD BRS3 HCRTR2NPY5R HTRlE CCR9 P2RY1 BDKRBl OPRKl TBXA2RHTR4 ADRA IBHCRTRl PTGERl GPRl 71 CMKLRl CXCR3 OPRDl HTR7 GRPR CNRl OPRMl AGTRl OPNlSW CCR8 OR5V1
AVPR2 MASl ADRBl DRD4 AVPRlB OR7A5 CCR3 GPR50 RRH P2RY6 SSTRl DRD5 MTNRlB MC5R GPR39 CXCR4 GPR37 ADRA2A C3AR1 ELA3A
LTB4R GPR35 GPR18 CCKBR NPY6R GPR30 NPY2R FPRLl HTRlB PPYRl ADRAlD CCKAR GPR45 FSHR GALR2 GPR68 CCRL2 TRHR ADRAlA DRD3 LYPDl CMKORl AGTRLl GPR65 P2RY11 FPRL2 CHRM3 SSTR2 GPR3 P2RY10 DRDl
GPR6 PTGDR LOC93164 ADORAl EDNRA CYSLTRl 0R7C1 0R2H1
P2RY5 0PN3 GPR85 GPR87 P2RY13 C5R1 CCRLl HRH3 GPR75 CCRlO HRH2 CYSLTR2 GALRl GPR63 GPR77 GPR173 GPR27 CHRM2 ORI lAl CHRM5 HTRlA
GPR24 CHRM4 GHSR HTR5A MTNRlA NMURl GPR42 GPR147 ORlFl OR12D3 MC3R HTRlF GNB2L1 GPR83 GPR34 SUCNRl NMUR2 P2RY 12 GPR81 GPR74 GPR174
EIF4E3 GPR92 CHRMl GPRlO GALT PHGDHLl Rgr ADORA2A GPR82
GALR3 GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS17 CAMK2G ATP2A2 ITPRl WDR42A CAMK2D CALMl CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 PRKARlA CACNAlD RYR2
GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GNAI l GJA4
GPCRDB_Class_C_Metabotropic_glutamate_pheromone GPCRDB_Class_C_Metabotropic_glutainate_pheromone GRM8 GPR51 GRM5 GPRC5A GABBRl GPRC5B GRM3 GRMl GRM7 GRM2 GRM4 CASR GPRC5C GPRC5DMGC35048 CALCRLLPHN3 LPHNl HRHl BDKRB2ADORA2B CX3CR1 CHML BLRl ADRA2CADRB2 ADORA3 PTGIR GPR17 GPR4 AVPRlA
P2RY2 PTAFR CCR7 GPR44 F2RL1 RHO OPRLl CNR2 DRD2 PTGER2 P2RY14 HTR2B BCL2L1 EDNRB F2RL2 ADRB3 OXTR CCBP2 NTSR2 HTR6 GPR23 GPRl 61 CCR2 CCR6 CCR5 IL8RB GPR37L1 RGR HTR2A PTGFR F2RL3 LHCGR
AGTR2 HTR2C NMBR NTSRl HTRlD BRS3 HCRTR2NPY5R HTRlE CCR9 P2RY1 BDKRBl OPRKl TBXA2RHTR4 ADRAIBHCRTRI PTGERl GPR171 CMKLRl CXCR3
OPRDl HTR7 GRPR CNRl OPRMl AGTRl OPNlSW CCR8 OR5V1 AVPR2
MASl ADRBl DRD4 AVPRlB OR7A5 CCR3 GPR50 RRH P2RY6 SSTRl DRD5 MTNRlB MC5R GPR39 CXCR4 GPR37 ADRA2A C3AR1 ELA3A LTB4R
GPR35 GPR18 CCKBR NPY6R GPR30 NPY2R FPRLl HTRlB PPYRl ADRAlD CCKAR GPR45 FSHR GALR2 GPR68 CCRL2 TRHR ADRAlA DRD3 LYPDl
CMKORl AGTRLl GPR65 P2RY11 FPRL2 CHRM3 SSTR2 GPR3 P2RY10 DRDl
GPR6 PTGDR LOC93164 ADORAl EDNRA CYSLTRl OR7C1 OR2H1
P2RY5 0PN3 GPR85 GPR87 P2RY13 C5R1 CCRLl HRH3 GPR75 CCRlO HRH2 CYSLTR2 GALRl GPR63 GPR77 GPR173 GPR27 CHRM2 ORI lAl CHRM5 HTRlA GPR24 CHRM4 GHSR HTR5A MTNRlA NMURl GPR42 GPR147 ORlFl OR12D3
MC3R HTRlF GNB2L1 GPR83 GPR34 SUCNRl NMUR2 P2RY 12 GPR81 GPR74 GPR174 EIF4E3 GPR92 CHRMl GPRlO GALT PHGDHLl Rgr AD0RA2A GPR82
GALR3 GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 ITPRl WDR42A CAMK2D
CALMl CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 PRKARlA CACNAlD RYR2
GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GNAI l GJA4
GPCRDB_Other GPCRDB_0ther LGR7 PTGFR OR2A9P CHRM3 GPRl 33 EMR3 OR5E1P
OR2M4 0R8G1 GNRHR F2R CELSR2 EDNRA CELSRl EDGl GPRl 62 CELSR3 EBI2 ADORA3 GPR17 GPR56 GPR GPR143 LPHN2 CCR2 CCR5 IL8RB GRMl
NTSRl EMR2 CXCR3 GHRHR GRPR DRD4 CCR3 FY LPHN3 TSHR ELA3A
GPR18 CCKBR FSHR GPR135 GPRl 16 P2RY11 SSTR2 MASSl OR7E24 OR7E47P LOC441453 SMO ALG6 P2RY13 C5R1 LTB4R2 GPR88 RLN3R1 GPR132 GPR77
HRH4 CIDEB CHRM2 VNlRl TAAR5 GPR84 GPR145 GPR61 LGR6 PHGDHLl GPR73L1 CNRl OPRMl AGTRl OPNlSW CCR8 0R5V1 AVPR2 MASl
ADRBl AVPR1BOR7A5 GPR50 RRH P2RY6 SSTRl DRD5 MTNRlB MC5R
GPR39 CXCR4 GPR37 ADRA2A C3AR1 LTB4R GPR35 NPY6R GPR30 CMKLRl
NPY2R FPRLl HTRlB PPYRl ADRAlD CCKAR GPR45 GALR2 GPR68 GPR4
CCRL2 TRHR HTR2C ADRAlA TBXA2RHTR2A DRD2 DRD3 PTAFR BCL2L1 LYPDl CMKORl F2RL1 AGTRLl GPR161 PTGERl GPR65 FPRL2 GPR3 P2RY10
DRDl GPR6 LHCGR PTGDR LOC93164 ADORAl CYSLTRl GPR44
OR7C1 BLRl HRHl 0R2H1 HTR4 ADRB3 P2RY5 OPN3 GPR85 GPR87 CCRLl HRH3 GPR75 CCRlO HRH2 CYSLTR2 GALRl GPR63 GPR173 GPR27 ORI lAl
CHRM5 HTRlA GPR24 CHRM4 GHSR HTR5A MTNRlA NMURl GPR42 GPR147 ORlFl OR12D3 MC3R HTRlF GNB2L1 AGTR2 GPR83 GPR34 SUCNRl NMUR2 P2RY 12
GPR81 GPR74 GPR174 EIF4E3 F2RL2 GPR92 CHRMl GPRlO GALT Rgr HTR7 ADORA2B ADORA2A CCR7 GPR82 GALR3 GNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17 CAMK2G
ATP2A2 ITPRl WDR42A CAMK2D CALMl CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 PRKARlA CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GNAI l GJA4
G_Protein_Signaling G_Protein_Signaling PDE7A PDE8A GNB5 PDElC PDE4D
SLC9A1 PDE8B ADCY7 PRKD3 GNG12 AKAP12 GNG4 RHOA PPP3CA PRKCBl PDElA AKAP6 KRAS AKAP8 PRKCH PRKCA ARHGEFl ITPRl SBF2 PRKCE GNG7 PRKCZ GNBl PRKARlA CALM3 CALMl GNB2 GNAI2 GNAI3 SARAl AKAPl
LOC552891 PRKCD GNAQ CSDEl NRAS PRKACB PALM2-AKAP2 PRKACA
AKAPI l PRKAR2B PDE4B GNAI l ADCY9 PDE4A GNAOl PRKAR2A GNAZ
AKAPlO GNA15 AKAP7 PRKDl USP5 GNB3 PRKCG GNAL PDElB PDE4C ADCY8 GNAl 3 PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 AKAP3 AKAP5 AKAP9 ADCY6 ADCY3 PRKCI PRKCQ PRKARlB RRAS HRAS ADCY2 ADCYl
PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13
GNA12 GNG3 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 GNA14
WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2
CACNAlB CACNAlE YWHAH KCN J5 RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Galactose metabolism Galactose metabolism G6PC GALE HKl PFKP AKRlBl
GLBl PGMl GAA HK2 GALT GALKl GALK2 HK3 MGAM LCT LALBA PFKM GCK GLA FLJ32800 MARKl ITPRl PPP3CA SBF2 PRKCE GNG7
PRKCZ GNBl RHOA PRKARlA CALM3 CALMl GNB2 GNAI2 GNAI3 SARAl
AKAPl LOC552891 PRKCD GNAQ CSDEl NRAS PRKACB PALM2-AKAP2 PRKACA ARHGEFl AKAPI l PRKAR2B PDE4B ADCY7 AKAP8 GNB5
KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A GNAZ AKAPlO GNG4
GNA15 AKAP6 AKAP7 PRKDl USP5 GNB3 PRKCH PRKCG GNAL PDElB PDE4C ADCY8 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2
PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 PRKCI PRKCQ AKAP12 PRKD3 GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl
PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13
GNA12 GNG3 PDE7A GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC 144363 GNGT2
GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2
CACNAlB CACNAlE YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Ganglioside biosynthesis Ganglioside biosynthesis GALGT ST3GAL1 ST8SIA1 ST3GAL5
B3GALT4 ST6GALNAC4 HK3 MGAM LCT G6PC LALBA PFKM GCK
GLA FLJ32800 GALT MARKl GLBl ITPRl PPP3CA SBF2 PRKCE GNG7
PRKCZ GNBl RHOA PRKARlA CALM3 CALMl GNB2 GNAI2 GNAI3 SARAl
AKAPl LOC552891 PRKCD GNAQ CSDEl NRAS PRKACB PALM2-AKAP2 PRKACA ARHGEFl AKAPI l PRKAR2B PDE4B ADCY7 AKAP8 GNB5
KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A GNAZ AKAPlO GNG4
GNA15 AKAP6 AKAP7 PRKDl USP5 GNB3 PRKCH PRKCG GNAL PDElB PDE4C ADCY8 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2
PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 PRKCI PRKCQ AKAP12 PRKD3 GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl
PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13
GNA12 GNG3 PDE7A GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2
GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2
CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Globoside metabolism Globoside metabolism NAGA HEXA ST3GAL1 ST8SIA1
HEXB FUTl FUT2 GLA GBGTl PFKM GCK FLJ32800 GALT MARKl GLBl ITPRl PPP3CA SBF2 PRKCE GNG7 PRKCZ GNBl RHOA PRKARlA CALM3 CALMl GNB2 GNAI2 GNAI3 SARAl AKAPl LOC552891 PRKCD GNAQ
CSDEl NRAS PRKACB PALM2-AKAP2 PRKACA ARHGEFl AKAPI l
PRKAR2B PDE4B ADCY7 AKAP8 GNB5 KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A GNAZ AKAPlO GNG4 GNA 15 AKAP6 AKAP7 PRKDl USP5
GNB3 PRKCH PRKCG GNAL PDElB PDE4C ADCY8 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl
PDElA ADCY6 ADCY3 SLC9A1 PRKCI PRKCQ AKAP12 PRKD3 GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13 GNA12 GNG3 PDE7A GNGlO ADCY5 RTDRl
ADCY4 AKAP8L LOC144363 GNGT2 GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4 Glucocorticoid_Mineralocorticoid_Metabolism Glucocorticoid_Mineralocorticoid_Metabolism CYP 17Al HSDl 1B2 CYPI lAl HSD3B1 HSDI lBl HSD3B2 CYP11B2 ST3GAL1
FUT2 ST8SIA1 FUT1 GLA HEXA GBGTl PFKM GCK FLJ32800 GALT
MARKl GLBl ITPRl PPP3CA SBF2 PRKCE GNG7 PRKCZ GNBl RHOA PRKARlA CALM3 CALMl GNB2 GNAI2 GNAI3 SARAl AKAPl LOC552891 PRKCD GNAQ
CSDEl NRAS PRKACB PALM2-AKAP2 PRKACA ARHGEFl AKAPI l PRKAR2B PDE4B ADCY7 AKAP8 GNB5 KRAS GNAI l PDE4D ADCY9 PDE4A
GNAOl PRKAR2A GNAZ AKAPlO GNG4 GNA15 AKAP6 AKAP7 PRKDl USP5
GNB3 PRKCH PRKCG GNAL PDElB PDE4C ADCY8 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl
PDElA ADCY6 ADCY3 SLC9A1 PRKCI PRKCQ AKAP12 PRKD3 GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl PLCB3 MPPEl LOC346329 CHMPlB
IL18BP MGCl 1266 PDE7B GNG13 GNA12 GNG3 PDE7A GNGlO ADCY5 RTDRl
ADCY4 AKAP8L LOC144363 GNGT2 GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS 14 GJA4 Glutamate metabolism Glutamate metabolism GCLC GFPTl CAD GLS2 NADSYNl
GOTl GAD2 GLUL GOT2 EPRS GLUDl GSS GLS ALDH5A1 ALDH4A1
GCLM CPSl GADl ABAT GPT PPAT GLUD2 GMPS QARS PALM2-AKAP2 PRKACA ARHGEFl AKAPl 1 PRKAR2B PDE4B ITPRl ADCY7 AKAP8
GNB5 KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A GNAZ AKAPlO GNG4 GNA15 AKAP6 AKAP7 PRKDl USP5 GNB3 PRKCH PRKCE PRKCG GNAL
PDElB PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3
SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PRKD3 GNAQ GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A
CSDEl GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC 144363 GNGT2 PRKACB
PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4 Glutathione metabolism Glutathione metabolism IDHl GCLC MGSTl GPXl GSTPl
GPX4 GPX3 MGST3 GSS G6PD GSTM3 GPX2 ANPEP GSTA4 GSTTl GSTA2 GCLM GSTM4 MGST2 GSTM2 GSTMl GSTT2 GSTM5 GGTl GSTZl IDH2 GGT2 GSTAl GSTA3 GSTO2 NADSYNl GMPS CPSl GLS GLUL GAD2 PPAT
GLUD2 PALM2-AKAP2 PRKACA ARHGEFl AKAPI l PRKAR2B PDE4B ITPRl ADCY7 AKAP8 GNB5 KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A
GNAZ AKAPlO GNG4 GNA15 AKAP6 AKAP7 PRKDl USP5 GNB3 PRKCH PRKCE (S) PRKCG GNAL PDElB PDE4C ADCY8 GNG7 GNAl 3 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA
ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP 12 AKAPl SARAl PRKD3 GNAQ GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl PLCB3 MPPEl LOC346329 CHMPlB IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12
GNG3 PDE7A CSDEl GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2
PRKACB PPP3CA GNB1 SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2
GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS 14 GJA4 Glycerolipid metabolism Glycerolipid metabolism DGKH DGKB DGKE LIPC AGP AT3
DGKG AKRlBl ALDH2 GLBl AKRlAl ALDH3A2 DGKA LPL DGATl PNLIP
ADHlC PNLIPRPl ALDH1A2 GK ADH6 DGKZ DGKQ ADHlA DGKD
PPAP2A PPAP2B PPAP2C ADHlB ALDHlBl ADH7 PNLIPRP2 ALDHlAl
GLA AGPATl LIPG ADH4 ADHFEl AKAP 8 GNB5 KRAS GNAI l PDE4D ADCY9 PDE4A GNAOl PRKAR2A GNAZ AKAPlO GNG4 GNA15 AKAP6 AKAP7 PRKDl
USP5 GNB3 PRKCH PRKCE PRKCG GNAL PDElB PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3
AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PRKD3 PDE4B ITPRl GNAQ GNG12 PDE8A PRKARlB RRAS HRAS ADCY2 PDE8B ADCYl PLCB3 MPPEl AKAPI l PRKACA LOC346329
CHMPlB IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A
CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2
PRKACB PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2
GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75
ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCN J5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3 CAMK2B RGS14 GJA4
Glycerophospholipid metabolism Glycerophospholipid metabolism DGKH DGKB DGKE
PCYTlA AGP AT3 GPDl DGKG PAFAHlBl CDIPT LYPLA2 PISD LYPLAl DGKA
PLA2G2A CHKB CHKA LCAT LYPLA3 PLA2G6 PAFAH2 ACHE AGPS CDSl
PLA2G5 CLC PLA2G1B DGKZ DGKQ PEMT DGKD PPAP2A PPAP2B PPAP2C CPTlB PLA2G4A CDS2 AGPATl ETNKl LGALS13 PLA2G3 CHAT USP5
GNB3 PRKCH PRKCE PRKCG GNAL PDElB PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3
AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP 12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO
GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA LOC346329 AKAP6 PRKDl
CHMPlB ILl 8BP MGCl 1266 PDE7B GNG 13 PRKCZ GNAl 2 GNG3 PDE7A
CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2
PRKACB PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
Glycine_serine and threonine metabolism Glycine_serine and threonine metabolism GAMT
ATP6V0C MAOB SARS TARS PISD ABPl CHKA AMT MAOA GLDC
AOC3 PSPH GCAT ALASl CTH BHMT DAO AGXT AOC2 PEMT GARS DLD SHMTl ALAS2 SHMT2 AGXT2 DMGDH CDS2 GPDl AGPATl LYPLA2 PL A2G5
PLA2G6 DGKB LCAT ETNKl AGP AT3 LGALS 13 PLA2G3 CHAT PCYTlA AGPS
CDSl DGKQ PPAP2B DGKG DGKZ PAFAHlBl USP5 GNB3 PRKCH PRKCE
PRKCG GNAL PDElB PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP 12 AKAPl SARAl PDE4D
PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS
AKAPI l ADCY9 PRKACA LOC346329 AKAP6 PRKDl CHMPlB ILl 8BP
MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2
GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS 14 GJA4 Glycogen_Metabolism Glycogen_Metabolism PPP2R5C PHKA2 PPP2R2B
PPP2R2C PPP2R5E PPP2R3B CALM3 CALMl PPP2R1A PPP2CB PYGB SARAl GYG GYSl PGMl PPP2R5A GSK3A PPP2R2A PPP2R5D
PHKB PPP2R1B PYGL GBEl AGL PHKG2 PPP2R5B PHKAl UGP2
PYGM PPP2R4 CALM2 PHKGl PPP2R3A PPP2CA LOC441485 GSK3B GYG2
GYS2 SUMF2 PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 PRKCI PRKCQ AKAP 12 AKAPl PDE4D PRKD3 AKAP7 PDE4B ITPRl
GNAQ PDE4A GNG 12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2
PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB PRKCH IL18BP MGCl 1266
PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl
SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGSl 7 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4 Glycolysis / Gluconeogenesis Glycolysis / Gluconeogenesis G6PC PDHAl FBP2 ALDH3B1 LDHA HKl PGKl TPIl PGAMl ALDOA LDHB PFKP ENOl PKM2 ENO2
ALDH2 AKRlAl PGMl ALDOC ALDH3A2 HK2 ALDH1A3 BPGM SNRPF
ENO3 ALDOB ALDH3B2 ACYPl ALDH3A1 HK3 ADHlC ACYP2 ALDH1A2
LDHC ADH6 ADHlA PKLR GPI PDHB DLD ADHlB ALDHlBl FBPl
ADH7 PFKM DLAT GCK ALDHlAl GAPDH PDHA2 TAF9L ADH4 ADHFEl EXOSCl MAP3K15 MARKl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA
PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3
AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG 12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6
PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12
GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41
GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2
CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Glycolysis_and_Gluconeogenesis Glycolysis_and_Gluconeogenesis G6PC PDHAl NIFIE 14
FBP2 GOTl LDHA HKl GOT2 PGKl TPIl PGAMl ALDOA MDHl LDHB PFKP PFKL TNFAIPl ENOl PKM2 ENO2 ALDOC HK2 PDHX SNRPF PC
ENO3 ALDOB PGAM2 HK3 LDHC GAPDHS PKLR GPI PCKl PDHB MDH2 DLD FBPl LDHAL6B PFKM DLAT GCK GAPDH PDH A2 PGK2
TAF9L EXOSCl MAP3K15 MARKl ADH4 ADHFEl ALDH3B1 BPGM AKRlAl
PPP2R5B PDE4C ADCY8 GNG7 GNAl 3 PRKCA PPP3CC AKAP4 GNB5 KCNJ3
GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA
ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS
PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB PRKCH
ILl 8BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-
AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG
PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4
Glycosaminoglycan degradation Glycosaminoglycan degradation ARSB IDS HEXA
GLBl HEXB GUSB GNS NAGLU IDUA GALNS ALDOB PGAM2 HK3 FBP2 G6PC LDHC GAPDHS PKLR GPI PCKl GOTl PDHB MDH2 DLD FBPl LDHAL6B PFKM PFKL DLAT GCK GAPDH TPIl LDHB PKM2
PDHA2 ALDOA PGK2 ENOl PGKl TAF9L MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C
ADCY8 GNG7 GNAl 3 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ
PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B
ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE
LOC346329 AKAP6 PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B
GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2
PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92
GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl
Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39
SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2R RGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4 Glycosphingolipid metabolism Glycosphingolipid metabolism SPTLCl ASAHl GLBl SPTLC2 GALC ARSA UGCG GAL3ST1 ARSE ARSD NEU3 NEUl GBA
PPAP2A PPAP2B SMPDl PPAP2C GLA NEU2 NEU4 DLAT GCK ALDOB GAPDH TPIl MDH2 LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3B1
BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9
PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl
KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl
PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB
PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24
CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4 Glyoxylate and dicarboxylate metabolism Glyoxylate and dicarboxylate metabolism MTHFDlL
ACO2 MDHl GRHPR MTHFDl ACOl CS MDH2 HAOl HA02 PPAP2C
GBA PPAP2A ASAHl GALC PPAP2B GLA NEU3 SPTLC2 SMPDl NEU2 UGCG NEU4 ARSD ARSA GLBl DLAT GCK ALDOB GAPDH TPIl LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3 Bl BPGM AKRlAl PPP2R5B PDE4C
ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNGl 2 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE
LOC346329 AKAP6 PRKDl CHMPlB PRKCH ILl 8BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2
PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92
GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39
SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2R
RGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16
SLC8A3 CACNAlD RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJA4
Heme_BiosynthesisHeme_Biosynthesis UROS HMBS FECH CPOX PPOX ALASl UROD
ALAS2 ALAD PPAP2C GBA PPAP2A ASAHl GALC PPAP2B GLA NEU3 SPTLC2 SMPDl NEU2 UGCG NEU4 ARSD ARSA GLBl DLAT GCK ALDOB GAPDH TPIl MDH2 LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3B1
BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4
GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9
PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl
KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB
PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl
PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB
PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
High-mannose type N-glycan biosynthesis High-mannose type N-glycan biosynthesis MAN IAl
MANlBl FECH CPOX PPOX ALASl UROD ALAS2 ALAD UROS PPAP2C
GBA PPAP2A ASAHl GALC PPAP2B GLA NEU3 SPTLC2 SMPDl NEU2 UGCG NEU4 ARSD ARSA GLBl DLAT GCK ALDOB GAPDH TPIl MDH2 LDHB
PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3B1 BPGM AKRlAl
PPP2R5B PDE4C ADCY8 GNG7 GNAl 3 PRKCA PPP3CC AKAP4 GNB5 KCNJ3
GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3
AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS
PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l
ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB PRKCH
IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2- AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG
PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPRl 61 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5
RGSl 7 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3
RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B
RGS14 GJA4 Histidine metabolism Histidine metabolism HNMT MAOB ALDH3B1 ALDH2 HARS ALDH3A2 ALDH1A3 ABPl MAOA A0C3 ALDH3B2 DDC
ALDH3A1 ASPA HAL ALDH1A2 AOC2 HDC HARSL ALDHlBl
ALDHlAl CNDPl ARSD PPAP2B ARSA SPTLC2 GLBl DLAT GCK ALDOB
GAPDH TPIl MDH2 LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4
GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9
PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB
PRKCH ILl 8BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP 8L LOC 144363 GNGT2 PRKACB
PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24
CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANX A6 SFN CACNB3
CAMK2B RGS14 GJA4 Hypertrophy_model Hypertrophy_model ATF3 ADAMlO WDRl CYR61
EIF4E IFRDl ILlRl DUSP14 JUND HBEGF ANKRDl IL18 GDF8 MYOG
NR4A3 ILIA VEGF TCF8 EIF4EBP1 SPTLC2 GLBl DLAT GCK ALDOB
GAPDH TPIl MDH2 LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl PDHAl ADH4 ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA
PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3
AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP 12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6
PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12
GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41
GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2
CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Indole and ipecac alkaloid biosynthesis Indole and ipecac alkaloid biosynthesis DDC WDRl CYR61
EIF4E IFRDl ADAMlO ATF3 ILlRl DUSP14 JUND HBEGF ANKRDl
IL18 GDF8 MYOG NR4A3 ILIA VEGF TCF8 EIF4EBP1 SPTLC2 GLBl
DLAT GCK ALDOB GAPDH TPIl MDH2 LDHB PKM2 PDHA2 ALDOA PGK2 ENOl PGKl TAF9L DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl
PDHAl ADH4 ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C ADCY8
GNG7 GNA13 PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP 12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B
ADCYl PLCB3 AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE
LOC346329 AKAP6 PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B
GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92
GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl
Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 AD0RA2B AD0RA3 GPR39
SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2R
RGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4
Inflammatory_Response_Pathway Inflammatory_Response_Pathway CD80 ZAP70 COLlAl
FNl LAMCl THBSl LAMBl COL3A1 LAMC2 IL4R TNFRSFlB IL2RG VTN LCK CD40 IL2RB CD86 IL2RA CD28 IL4 TNFRSFlA IL2 CD40LG
IL5RA IL5 THBS3 LAMA5 LAMB2 GAPDH PKM2 TAF9L PGKl DLD GPI MDHl EXOSCl ENO3 MAP3K15 ALDOA MARKl ENOl PDHAl ALDOB ADH4
ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13
PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ
AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3
AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329
AKAP6 PRKDl CHMPlB PRKCH ILl 8BP MGCl 1266 PDE7B GNG 13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L
LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT
CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13
LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A
HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS17 CAMK2G ATP2A2
WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Inositol metaboHsmlnositol metabolism TPIl ALDOA ALDOC C14orf45 ALDH6A1 ALDOB
TNFRSFlB IL2RG VTN LCK CD40 IL2RB CD86 IL2RA CD28 CD80 LAMC2 IL4 TNFRSFlA IL2 CD40LG IL5RA IL5 THBS3 LAMA5 FNl
COL3A1 LAMBl ZAP70 THBSl LAMB2 IL4R LAMCl GAPDH PKM2 TAF9L PGKl DLD GPI MDHl EXOSCl ENO3 MAP3K15 MARKl ENOl PDHAl ADH4
ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13
PRKCA PPP3CC AKAP4 GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9 PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ
AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl PLCB3
AKAPlO GNAI l MPPEl KRAS AKAPI l ADC Y9 PRKACA PRKCE LOC346329
AKAP6 PRKDl CHMPlB PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8L
LOC144363 GNGT2 PRKACB PRKCG PPP3CA GNBl SBF2 PRKARlA
GNA14 WDR41 GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT
CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13
LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1
ATP2B2 CACNAlB CACNAlE YWHAH KCNJ5 RGS 17 CAMK2G ATP2A2
WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Inositol phosphate metabolism Inositol phosphate metabolism PIP5K2BPIK3C2A ITPKB INPP5A PLCG2 INPP4B INPPLl PLCGl INPPl IMPAl OCRL PLCB4 PLCB2
PIK3CA PIK3C2BINPP4A PLCDl ITPKA PIK3CG PIK4CA PLCBl PIK3CB PLCB3 LOC375133 PIK3C2G MIOX SERPINDl LAMA5 COL3A1 THBSl FNl LAMBl TNFRSFlA
IL4R LAMCl CD40 GAPDH PKM2 TAF9L PGKl DLD GPI MDHl EXOSCl ENO3 MAP3K15 ALDOA MARKl ENOl PDHAl ALDOB ADH4 ADHFEl ALDH3B1 BPGM AKRlAl PPP2R5B PDE4C ADCY8 GNG7 GNA13 PRKCA PPP3CC AKAP4
GNB5 KCNJ3 GNG5 GNGTl PRKACG CALM2 PDElC AKAP3 AKAP5 AKAP9
PRKCBl PDElA ADCY6 ADCY3 SLC9A1 CALMl PRKCI PRKCQ AKAP12 AKAPl SARAl PDE4D PRKD3 AKAP7 PDE4B ITPRl GNAQ PDE4A GNG12 PDE8A PRKARlB RRAS HRAS PRKAR2A ADCY2 PDE8B ADCYl AKAPlO GNAI l MPPEl KRAS AKAPI l ADCY9 PRKACA PRKCE LOC346329 AKAP6 PRKDl CHMPlB
PRKCH IL18BP MGCl 1266 PDE7B GNG13 PRKCZ GNA12 GNG3 PDE7A CSDEl
PALM2-AKAP2 GNGlO ADCY5 RTDRl ADCY4 AKAP8LLOC144363 GNGT2 PRKACB
PRKCG PPP3CA GNBl SBF2 PRKARlA GNA14 WDR41 GPR161 FPRL2 GPR24
CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B
ADORA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RRGS3 RYR3 SLC8A1 ATP2B2 CACNAlB CACNAlE
YWHAH KCN J5 RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3 CAMK2B RGS14 GJA4
Integrin-rnediated_cell_adhesion_KEGG Integrin-mediated_cell_adhesion_KEGG SDCCAG8
ITGBl FLJ14825 ITGAL ITGAI l PAK6 ITGA9 ITGB2 CDC42 SOSl ITGB6
SRC PAK2 FYN SORBSl PTK2 ITGAD ITGAX ITGB8 DOCKl DKFZp434E1119 RACl PIK3R2 ROCKl CAPNSl CAPNl ZYX RAPlB VCL PXN ITGB5 ILK ITGA5 SEPPl SHCl ITGA3 ITGA6 VASP CRK CSK ITGAV MAP2K2MAP2K1
ROCK2 CAPN6 CAVl PAK4 TLNl CAV2 CAPN7 PDPKl RAPGEFl ITGB3
MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE CAPN5 VA V2 MAP2K6ITGB7 ITGAM ITGA4 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO MAPK6 AKTl MAPK7 RAC2 MAP2K3 CAPNI l CAPN9 CAV3 CAPN2 PAKl ITGA7 CAPN3 AKT3 PAK3 ITGA8 SNAPC5 GRB2 VAV3 TNSl CAPNlO BCARl MGC17301 FLJ40125 MYLK2
DKFZP564G2022 TAFlO EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Irinotecan_pathway_PharmGKB Irinotecan_pathway_PharmGKB ABCCl UGTl A9 BCHE
CYP3A5 CYP3A4 UGT1A6 ABCC2 CES4 UGTlAl UGT1A3 CESl CES2 ABCG2 CYP3A5P2
SRC DKFZp434E1119 RACl PIK3R2 ROCKl CAPNSl CAPNl ZYX RAPlB VCL
PXN ITGB5 ILK ITGA5 SEPPl SHCl ITGA3 ITGA6 VASP CRK CSK
ITGAV MAP2K2MAP2K1 ROCK2 ITGB2 CAPN6 CAVl PAK4 DOCKl TLNl CAV2 CAPN7 PDPKl RAPGEFl ITGB3 MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE
CAPN5 VAV2 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12
SHC3 RHO ITGA2B ITGAlO MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l
CAPN9 ITGB6 CAV3 CAPN2 CDC42 PAKl ITGA7 FYN ITGAX CAPN3 SORBSl
ITGBl AKT3 SOSl ITGAL PAK3 ITGA8 SNAPC5 GRB2 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301 SDCCAG8 FLJ40125
MYLK2 DKFZP564G2022 TAFlO EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161
FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH
SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Keratan sulfate biosynthesis Keratan sulfate biosynthesis FUT8 ST3GAL3 B4GALT5
ST3GAL1 B3GNT1 UGTl A6 CYP3A5 SRC DKFZp434El 119 RACl PIK3R2 ROCKl
CAPNSl CAPNl ZYX RAPlB VCL PXN ITGB5 ILK ITGA5 SEPPl SHCl
ITGA3 ITGA6 VASP CRK CSK ITGAV MAP2K2MAP2K1 ROCK2 ITGB2 CAPN6 CAVl PAK4 DOCKl TLNl CAV2 CAPN7 PDPKl RAPGEFl ITGB3 MAPK4
MAPK10GIT2 ITGB4 ITGA2 ITGAE CAPN5 VAV2 MAP2K6ITGB7 ITGAM ITGB8
ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO MAPK6 AKTl
MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 CAPN2 CDC42 PAKl
ITGA7 FYN ITGAX CAPN3 SORBSl ITGBl AKT3 SOSl ITGAL PAK3 ITGA8 SNAPC5 GRB2 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301
SDCCAG8 FLJ40125 MYLK2 DKFZP564G2022 TAFlO EPHAl KIAA0470
LOC441708 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl
PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92
GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39
SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2R
GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3
PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl
PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4
Krebs-TCA_Cycle Krebs-TCA_Cycle OGDH PDHAl PDK4 AC02 MDHl SDHA IDH3B
SDHC SDHD IDH3A IDH3G PDK2 SDHB SUCLA2 FH PDHX WDR50 PC
PDK3 PDKl CS PDHB MDH2 DLD IDH2 DLAT SUCLG2 PDHA2 RPAl DLSTP SUCLGl PPM2C SDHAL2 TFRC PDP2 MAP3K15 LOC257177 CAPN7
PDPKl RAPGEFl ITGB3 MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE CAPN5
VAV2 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3
RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l
CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 FYN ITGAX CAPN3 ROCK2 SORBSl PXN ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2
PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl
CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301 SDCCAG8 ITGA3
FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022
TAFlO ITGB2 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2
GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75
AD0RA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCN J3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADC Y3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3 CAMK2B RGS14 GJA4
Limonene and pinene degradation Limonene and pinene degradation SDS ECHSl ALDH2
ALDH3A2 EHHADH ALDH1A2 HADHA ALDHlBl ALDHlAl FH PDHX WDR50 PC PDK4 PDK3 PDKl CS PDHB MDH2 DLD IDH3B
IDH2 DLAT SUCLG2 PDK2 SDHB IDH3G PDHA2 RPAl DLSTP SDHC SUCLGl PPM2C SDHAL2 TFRC PDP2 MDHl MAP3K15 LOC257177 OGDH PDHAl
CAPN7 PDPKl RAPGEFl ITGB3 MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE
CAPN5 VAV2 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2
CAPNl 1 CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 FYN ITGAX CAPN3 ROCK2 SORBSl PXN ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK
DKFZP564G2022 TAFlO ITGB2 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAH GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Lysine biosynthesis Lysine biosynthesis KARS AADAT ALDH3A2 EHHADH SDS
ALDH1A2 HADHA ALDHlBl ALDHlAl FH PDHX WDR50 PC
PDK4 PDK3 PDKl CS PDHB MDH2 DLD IDH3B IDH2 DLAT SUCLG2
PDK2 SDHB IDH3G PDHA2 RPAl DLSTP SDHC SUCLGl PPM2C SDHAL2 TFRC PDP2 MDHl MAP3K15 LOC257177 OGDH PDHAl CAPN7 PDPKl RAPGEFl
ITGB3 MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE CAPN5 VAV2 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPKl 2 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 FYN ITGAX CAPN3 R0CK2 SORBSl PXN ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2PAK3 ITGA8 SNAPC5
SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3
GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
Lysine degradation Lysine degradation ACATl SDS ATP6V0C PLODl ECHSl ALDH2 ALDH9A1 ALDH3A2 GCDH EHHADH BBOXl ALDH1A2 HADHA
ALDHlBl SHMTl AASS ALDHlAl SHMT2 DLSTP AADAT PDK2 SDHB FH
IDH3G PDHA2 SUCLG2 RPA1 SDHC SUCLGl PPM2C PDK3 SDHAL2 PDK1 TFRC DLD PDP2 MDHl MAP3K15 LOC257177 OGDH PDHAl CAPN7 PDPKl
RAPGEFl ITGB3 MAPK4 MAPK10GIT2 ITGB4 ITGA2 ITGAE CAPN5 VAV2 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO
ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 FYN ITGAX CAPN3 R0CK2 SORBSl PXN ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VA V3 TNSl CAPNlO PAK6 ITGAI l BCARl FLJ14825 MGC17301 SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 EPHAl KIAA0470 LOC441708 AKAP8L PRKARlA PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3 CAMK2B RGS14 GJA4
MAPK_Cascade MAPK_Cascade MAPKl MBP KRAS MAP3K2RAF1 JUN TIMPl
ARAF MAP2K2MAPK14CSDE1 NRAS MAP2K1 MAP2K4MAP3K3ELK1 SIPAl MAPKlO MAP3K12 MAP2K6BRAF MAPK12RASA3 MAP2K3MAP2K7MAP2 MAPK3 RRAS
HRAS PLCB3 SNAPC5 MAP3K1 MGC10986 LOC144363 LYK5 ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6
AKTl MAPK7 RAC2 PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK
DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8L
PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Matrix_Metalloproteinases Matrix_Metalloproteinases MMP21 MMP2 MMP 14 TIMP3 TIMPl
ARAF TIMP2 MMP 15 MMPI l MMP9 MMP7 MMPl MMP 19 MMP 12 MMPlO MMP3 MMP13 MMP17 TIMP4 MMP16 TNF MMP23A MMP8 MMP20 MMP25 MMP24 BSG TCF20 MMP28 MMP26 MMP27 SYN2 KRAS SNAPC5 MAP3K1 MAP2K3MAP2K7
MGC10986 MAP3K2CSDE1 MAP2 RASA3 MAP3K3LOC144363 MBP BRAF
LYK5 MAPK10MAP2K2RAF1 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 PTK2 CAPNl 1 CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3
SOSl ROCKl SRC ITGAL PAK3 ITGA8 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO P AK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl
VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8L PRKAR1A PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2
ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS 14 GJA4 Methane metabolism Methane metabolism ATP6V0C PRDX5 PRDX6 PRDX2
CAT MPO PRDXl ADH5 SHMTl LPO SHMT2 TNF MMP23A MMP8
MMP20 MMP25 MMP16 MMP24 BSG TCF20 MMP14 MMP28 MMP26 MMP27 TIMP2 SYN2 MMPI l TIMP3 MMP15 KRAS SN APC5 MAP3K1 MAP2K3MAP2K7 MGC 10986 MAP3K2CSDE1 MAP2 RASA3 MAP3K3 LOC144363 MBP BRAF LYK5 MAPKlO MAP2K2RAF1 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12
SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITG A7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VA V3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2
CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB
MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D
WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCN J3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
Methionine metabolism Methionine metabolism AHCY MARS DNMTl MTR MATlA
CTH BHMT MAT2B DNMT3A DNMT3B SHMT2 PRDX2 CAT SHMTl
PRDX5 PRDX6 TNF MMP23A MMP8 MMP20 MMP25 MMP 16 MMP24 BSG TCF20 MMP14 MMP28 MMP26 MMP27 TIMP2 SYN2 MMPI l TIMP3 MMP15 KRAS
SNAPC5 MAP3K1 MAP2K3MAP2K7MGC10986 MAP3K2CSDE1 MAP2 RASA3 MAP3K3
LOC144363 MBP BRAF LYK5 MAPK 10MAP2K2 RAFl MAP2K6ITGB7 ITGAM
ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN
ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8L
PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Mitochondrial_fatty_acid_betaoxidation Mitochondrial_fatty_acid_betaoxidation ACSL4
ACADVL HADHSC SCP2 ACSL3 ACSLl MGC5139 ACADS ACADM
CPTlA SLC25A20 CPT2 EHHADH ACADL HADHA DCI PECR MMP14
MMP28 MMP26 MMP27 TIMP2 SYN2 MMPI l TIMP3 MMP15 KRAS SNAPC5 MAP3K1 MAP2K3MAP2K7MGC10986 MAP3K2CSDE1 MAP2 RASA3 MAP3K3 LOC 144363 MBP BRAF LYK5 MAPKlO M AP2K2 RAFl MAP2K6ITGB7 ITGAM ITGB8 ITGA4
PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 PTK2 CAPNl 1 CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825
RAPGEFl VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA
GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D
CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN
CACNB3CAMK2B RGS14 GJA4
Monoamine_GPCRs Monoamine_GPCRs HTR6 CHRM3 HTR4 BCL2L1 HRHl
ADRA2CADRB2 DRD2 HTR2B ADRB3 HTR2A HTR2C HTRlD HTRlE ADRA1BHTR7 ADRBl DRD4 DRD5 ADRA2A HTRlB ADRAlD ADRAlA DRD3
DRDl LOC93164 HRH2 CHRM2 CHRM5 HTRlA CHRM4 HTR5A HTRlF CHRMl
CSDEl MAP2 RASA3 MAP3K1 MAP2K7MAP3K2MAP3K3LOC144363 MBP BRAF
LYK5 MAPK10MAP2K2RAF1 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPKl 2 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7
GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2
CAPN7 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPRl 61 FPRL2 GPR24 CYSLTRl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85
CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A CCR7 EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCN J3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB
CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4 N-Glycan biosynthesis N-Glycan biosynthesis FUT8 B4GALT5 MGAT3 MGC52110
MGATl ST6GAL1 DPMI MGAT2 MGAT5 MANlAl DDOST RPN2 DPAGTl
GCSl ALG5 MANlBl MGAT4A MGAT4B BCL2L1 DRD3 CHRM3
DRDl LOC93164 HRHl DRD2 HTR4 ADRB3 HRH2 CHRM2 CHRM5 HTRlA
CHRM4 HTR5A HTRlF ADRBl CHRMl HTR7 HTR2C ADRAlA CSDEl MAP2 RASA3 MAP3K1 MAP2K7MAP3K2MAP3K3LOC144363 MBP BRAF LYK5 MAPKlO
MAP2K2RAF1 MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNl 1 CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SNAPC5 SHCl GRB2 ITG A6 PAK4 ZYX
CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl
VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKF2P564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1
SSTRl Rgr P2RY13 LTB4R NPY6R GPR75 AD0RA2B ADORA3 GPR39
SSTR2 ADORA2A CCR7 EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3
PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
N-Glycan degradation N-Glycan degradation HEXA GLBl HEXB FUCAl MANBA
AGA NEU3 NEUl FLJ21865 NEU2 NEU4 FUCA2 MGAT3 GCSl MGAT2 RPN2 ST6GAL1 MGAT5 ALG5 MANlBl MGAT4A MGAT4B
B4GALT5 MANlAl MGATl FUT8 DPMI BCL2L1 DRD3 CHRM3 DRDl
LOC93164 HRHl DRD2 HTR4 ADRB3 HRH2 CHRM2 CHRM5 HTRlA CHRM4
HTR5A HTRlF ADRBl CHRMl HTR7 HTR2C ADRAlA CSDEl MAP2 RASA3
MAP3K1 MAP2K7MAP3K2MAP3K3LOC144363 MBP BRAF LYK5 MAPKl 0MAP2K2 RAFl MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3
RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl
VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R NPY6R GPR75 ADORA2B ADORA3 GPR39
SSTR2 AD0RA2A CCR7 EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3
PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Nicotinate and nicotinamide metabolism Nicotinate and nicotinamide metabolism NMNAT2
NT5C NADSYNl NMNATl NP NNMT QPRT ENPPl AOXl CD38
RBAK NT5M ENPP3 MANlBl MGAT4A MGAT4B B4GALT5 MANlAl MGATl FUT8 DPMI BCL2L1 DRD3 CHRM3 DRDl LOC93164
HRHl DRD2 HTR4 ADRB3 HRH2 CHRM2 CHRM5 HTRlA CHRM4 HTR5A HTRlF ADRBl CHRMl HTR7 HTR2C ADRAlA CSDEl MAP2 RASA3 MAP3K1 MAP2K7
MAP3K2MAP3K3LOC144363 MBP BRAF LYK5 MAPKl 0MAP2K2RAF1 MAP2K6
ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPKl 2 SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6
CAV3 RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL
PAK3 ITGA8 SNAPC5 SHCl GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl
CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VA V2 CAPN5
MGC17301 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470
LOC441708 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl
PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl GPR92 GPRlO
GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A CCR7 EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3
PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE
PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Nitrogen metabolism Nitrogen metabolism CA8 CA6 GLS2 GLUL GLUDl
GLS CAl 2 AMT CA3 CPSl ASNS CA9 CAl CTH CA4 HAL
CA5B CA5A CA7 CA2 GLUD2 CA14 HTRlF ADRBl CHRMl HTR7 HTR2C ADRAlA CSDEl MAP2 RASA3 MAP3K1 MAP2K7MAP3K2MAP3K3 LOC144363
MBP BRAF LYK5 MAPKl OM AP2K2 RAFl MAP2K6ITGB7 ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO PIK3R2 MAPK6 AKTl
MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3 RACl CAPN2 CDC42
PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4
ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3 ITGA8 SNAPC5 SHCl
GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 MGC17301 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl ILK
DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8L
PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R NPY6R
GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A CCR7 EDNRA
GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1
ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ
YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN
CACNB3CAMK2B RGS 14 GJA4
Novobiocin biosynthesis Novobiocin biosynthesis TAT GOTl GOT2 GLUDl GLS
CA12 AMT CA3 CPSl ASNS CA9 GLS2 CAl CTH CA4 HAL
CA6 CA5B CA5A CA7 CA2 GLUD2 GLUL CA14 CA8 HTRlF ADRBl CHRMl HTR7 HTR2C ADRAlA CSDEl MAP2 RASA3 MAP3K1 MAP2K7MAP3K2
MAP3K3LOC144363 MBP BRAF LYK5 MAPKl 0MAP2K2RAF1 MAP2K6ITGB7
ITGAM ITGB8 ITGA4 PAK2 ITGA9 RAC3 MAPK12SHC3 RHO ITGA2B ITGAlO
PIK3R2 MAPK6 AKTl MAPK7 RAC2 MAP2K3PTK2 CAPNI l CAPN9 ITGB6 CAV3
RACl CAPN2 CDC42 PAKl ITGA7 GIT2 FYN ITGAX CAPN3 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL PAK3
ITGA8 SNAPC5 SHC1 GRB2 ITGA6 PAK4 ZYX CAPN6 VAV3 TNSl CAPNlO
PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 MGC17301
ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl
DOCKl ILK DKFZP564G2022 TAFlO ITGB2 CAPN7 EPHAl KIAA0470 LOC441708 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl
PPP3CC GNAI l GPRl 61 FPRL2 GPR24 CYSLTRl GPR92 GPRlO GALT CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R NPY6R
GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A CCR7 EDNRA
GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ
YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D
CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN
CACNB3CAMK2B RGS14 GJA4
Nuclear_Receptors Nuclear_Receptors THRA ESRRA PPARA RORl RORA NR5A2 RARA NR1I3 NPMl NR3C1 NR4A1 RXRA NR1H3 RARG VDR NR4A2 NRlDl RARB
ESRl RXRG NR2C2 RORC NROBl THRB NR1I2 NR2E1 PPARD ALK HNF4A
PPARG NR2F2 RXRB NR2F6 NR2F1 NRl D2 NR5A1 ESR2 AR NRl H2 LOCI 50383
PGR ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3
SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2 RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX
ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VA V2 CAPN5 PAKl MGC 17301 ITGA9 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470
LOC441708 MAPK7 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS 14 GJA4
Nucleotide sugars metabolism Nucleotide sugars metabolism GALE GALT RORA RARA NR1I3 NPMl NR3C1 NR4A1 RXRA ESRRA NR1H3 THRA RARG VDR
NR4A2 NRlDl RARB ESRl RORl RXRG NR2C2 RORC NROBl PPARA THRB
NRl 12 NR2E1 PPARD ALK NR5A2 HNF4A PPARG NR2F2 RXRB NR2F6 NR2F1
NR1D2 NR5A1 ESR2 AR NR1H2 LOC150383 PGR ITGA7 GIT2 FYN
ITGAX CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5
SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITG A2B CAPN6 VAV3 TNSl
CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5
PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8L
PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl
PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 AD0RA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Nucleotide_GPCRsNucleotide_GPCRs ADORA2A P2RY5 ADORAl ADORA2B
ADORA3 P2RY2 GPR23 P2RY1 P2RY6 LTB4R RARA NR1H3 THRA RARG
VDR NR4A2 NRlDl RARB ESRl RORl RXRG NR2C2 RORC NROBl PPARA
NRl 13 THRB NRl 12 NR2E1 PPARD ALK NR5A2 HNF4A PPARG NR2F2 RXRB
NR2F6 NR2F1 NR1D2 NR4A1 NR5A1 RORA ESR2 AR NR3C1 NR1H2 NPMl LOC 150383 PGR ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8
ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC
ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4
MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl
FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl
PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4
KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 HTR7 NPY6R GPR75 GPR39 SSTR2 HTR2C CCR7
ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3
RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE
PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Nucleotide_Metabolism Nucleotide_Metabolism POLA HPRTl OAZl NME2 RRMl
SRM MTHFD2 ADSL DHFR POLG PRPS2 POLDl SAT POLB IMPDHl
FLJl 4668 ADSS RXRG NR2C2 RORC NROBl PPARA NRl 13 THRB NRl 12
NR2E1 PPARD ALK NR5A2 RARB HNF4A PPARG NR2F2 RXRB NR2F6 NR2F1 NR1D2 NR4A1 NR5A1 RORA ESR2 RORl AR ESRl RARA NR3C1 THRA
NR4A2 NR1H2 NPMl LOC150383 PGR NRlDl ITGA7 GIT2 FYN ITGAX
CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl
AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl
CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl
MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2
MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161
FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75
ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH
SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
O-Glycan biosynthesis O-Glycan biosynthesis ST3GAL1 GALNTl G ALNT3 GCNTl
GALNTlO GALNT7 GALNT2 GALNT6 GALNT4GALNT8 GALNT9 SAT RRMl POLB
DHFR RXRG NR2C2 RORC NROBl PPARA NR1I3 THRB NR1I2 NR2E1 PPARD ALK NR5A2 RARB HNF4A PPARG NR2F2 RXRB NR2F6 NR2F1 NR1D2 NR4A1
NR5A1 RORA ESR2 RORl AR ESRl RARA NR3C1 THRA NR4A2 NR1H2
NPMl LOC150383 PGR NRlDl ITGA7 GIT2 FYN ITGAX CDC42 CAPN9
CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl
ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l
BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301
ITG A9 ITG A2 SDCC AG8 ITG A3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl
TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7
EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2
GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75
ADORA2B ADORA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCN J3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG
GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS 14 GJA4
One carbon pool by folate One carbon pool by folate TYMS ATP6V0C MTHFDlL MTHFD2 MTHFDl DHFR MTR AMT ALDHlLl MTHFR SHMTl
SHMT2 Clorfl67PPARA NR1I3 THRB NR1I2 NR2E1 PPARD ALK NR5A2 RARB
HNF4A PPARG NR2F2 RXRB NR2F6 NR2F1 NR1D2 NR4A1 NR5A1 RORA ESR2
RORl AR ESRl RARA NR3C1 THRA NR4A2 NR1H2 NPMl NR2C2 LOC150383
RORC PGR NRlDl ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC
ITGAL MAP2K2RAC2 PAK3 ITG A8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4
MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl
FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2
SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4
KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl
CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR
OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 AD0RA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3 CAMK2B RGS14 GJA4
Ovarian_Infertility_Genes Ovarian_Infertility_Genes ATM CCND2 NCORl INHA EGRl
CDK4 MLHl NRIPl VDR GJA4 PRLR DAZL PTGER2 LHCGR ZP2 DMCl CDKNlB SMPDl NR5A1 MSH5 BMPR1BESR2 FSHR CEBPB PGR NR1D2
NR5A2 NR4A1 RORA PPARD PPARA RORl AR ESRl RARA NR3C1 HNF4A THRA NR2F2 RXRB NR4A2 RARB NR1H2 NPMl NR2C2 LOC150383 RORC
PPARG NR1I2 NRlDl ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8
ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC
ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4
MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO P AK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2
SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14
PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCN J3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14
Oxidative phosphorylation Oxidative phosphorylation ATP6V1C2 PP A2 NDUFAlO
ATP6V1B1 ATP6V0C NDUFB6ATP6V0A1 NDUFSl ATPl 2A ATP5 O ATP6V0B
ATP6V0E COX6A1 ATP6V1B2 SDHA COX8A COX7C NDUFA5COX6B1 ATP6V1F COX7A2 COX6C UQCRCl ATP6V1 A COX7B NDUFAl COX5B SDHB NDUFB7ATP6V1C1
NDUFV2NDUFB5COX5A COX7A1 ATP7B ATP7A UQCRB COX6A2 ATP4B ATP6AP1 ATP6V1E1 NDUFVl ATP6V1G1 ATP6V1D UQCRFSl ATP6V0D1
ATP6V1G2 NDUFA4ATP5E PP NDUFA8NDUFB2NDUFB4ATP6V0A4 ATP6V1H
SDHAL2 NDUFAI l TFRC ATP6V1G3 RORl PPARG NR3C1 ESRl NR4A2 RORA NR1I2 PGR PPARD LOC150383 NRlDl THRA ITGA7 GIT2 FYN
ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8L
PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS 14 GJA4
Pantothenate and CoA biosynthesis Pantothenate and CoA biosynthesis DPYD COASY ENPPl
DPYS BCATl PANK3 PANK4 PANK2 ENPP3 PANKl NDUFA5COX6B1 ATP6V1F COX7A2 COX6C UQCRCl ATP6V1 A C0X7B NDUFAl COX5B SDHB NDUFB7ATP6V1C1 NDUFV2NDUFS1 NDUFB6NDUFB5 COX5A COX7A1 ATP7B ATP6V0A1 ATP7A ATP6V1B1
UQCRB COX6A2 ATP12A ATP4B ATP6AP1 ATP6V1E1 NDUFV 1ATP6V IGl
ATP6V1D UQCRFSl ATP6V0D1 COX7C ATP6V0E ATP6V1G2
ATP50 NDUFA4ATP5E PP NDUFAlO NDUFA8NDUFB2NDUFB4ATP6V0A4
PP A2 ATP6V1H SDHAL2 COX6 Al NDUFAl 1 TFRC ATP6V1G3 ATP6V0C RORl PPARG NR3C1 ESRl NR4A2 RORA NR1I2 PGR PPARD LOC150383
NRlDl THRA ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3 ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41
ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 AD0RA2B ADORA3
GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANX A6 SFN CACNB3
CAMK2B RGS 14 GJA4
Pentose and glucuronate interconversions Pentose and glucuronate interconversions AKRlBl
GUSB UGT1A9 UGT1A6 UGT2B4 UGTlAl UGT2B15 UGT1A3 UGT1A8 ENPP3 BCATl PANKl PANK2 NDUFA5COX6B1 ATP6V1F COX7A2 COX6C UQCRCl ATP6V1A
COX7B NDUFAl COX5B SDHB NDUFB7ATP6V1C1 NDUFV2NDUFS1 NDUFB6NDUFB5 COX5A COX7A1 ATP7B ATP6V0A1 ATP7A ATP6V1B1 UQCRB COX6A2ATP12A
ATP4B ATP6AP1 ATP6V1E1 NDUFVl ATP6V1 Gl ATP6V1D UQCRFSl
ATP6V0D1 COX7C ATP6V0E ATP6V1G2 ATP5O NDUFA4ATP5E PP
NDUFAlO NDUFA8NDUFB2NDUFB4ATP6V0A4 PPA2 ATP6V1H SDHAL2 COX6A1 NDUFAl 1 TFRC ATP6V1G3 ATP6V0C RORl PPARG NR3C1
ESRl NR4A2 RORA NR1I2 PGR PPARD LOC150383 NRlDl THRA ITGA7
GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl
VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7
AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT
CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13
LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A
HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3
PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJ A4
Pentose phosphate pathway Pentose phosphate pathway PGLS H6PD FBP2 ALDOA PFKP
PGD TALDOl PGMl ALDOC G6PD PRPS2 ALDOB GPI PRPSl FBPl PFKM PRPSlLl RBKS MARKl NDUFB7ATP6V1C1 NDUFV2NDUFS1 NDUFB6NDUFB5
COX5A COX7A1 ATP7B ATP6V0A1 ATP7A ATP6V1B1 UQCRB COX6A2 ATP12A
ATP4B ATP6AP1 ATP6V1E1 NDUFVl ATP6V IGl ATP6V1D UQCRFSl
C0X5B ATP6V0D1 COX7C ATP6V0E SDHB ATP6V1G2 NDUFA5ATP5O
NDUFA4ATP5E PP NDUFAlO NDUFA8NDUFB2NDUFB4ATP6V0A4 PPA2 ATP6V1H SDHAL2 COX6A1 NDUFAI l TFRC ATP6V1G3 ATP6V0C
RORl PPARG NR3C1 ESRl NR4A2 RORA NR1I2 PGR PPARD LOC150383 NRlDl THRA ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3 ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825
RAPGEFl VAV2 CAPN5 PAKl MGCl 7301 ITGA9 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
Pentose_Phosρhate_Pathway Pentose_Phosphate_Pathway PGLS RPE TALI PGD TALDOl G6PD TKT RPIA LOC440001 SLC4A10 FLJ23861 ALDOB ALDOA
PRPSlLl RBKS H6PD GPI MARKl NDUFB7ATP6V1C1 NDUFV2NDUFS1
NDUFB6NDUFB5 COX5A C0X7A1 ATP7B ATP6V0A1 ATP7A ATP6V1B1 UQCRB
COX6A2 ATP12A ATP4B ATP6AP1 ATP6V1E1 NDUFV 1ATP6V IGl ATP6V1D
UQCRFSl COX5B ATP6V0D1 C0X7C ATP6V0E SDHB ATP6V1G2 NDUFA5ATP5O NDUFA4ATP5E PP NDUFAlO NDUFA8NDUFB2NDUFB4ATP6V0A4
PP A2 ATP6V1H SDHAL2 COX6 Al NDUFAI l TFRC ATP6V1G3 ATP6V0C
RORl PPARG NR3C1 ESRl NR4A2 RORA NR1I2 PGR PPARD LOC150383 NRlDl THRA ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3
ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41
ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4
Peptide_GPCRs Peptide_GPCRs BRS3 TAC4 GNRHR CX3CR1 ATP8A1 GNB2L1 GALT EDNRB EDNRA CCRl FPRl AGTRl MClR BDKRB2BLR1 AVPR1ACCR7 OPRLl
OXTR NTSR2 CXCR6 CCR2 CCR6 CCR5 IL8RB LHCGR AGTR2 NMBR NTSRl NPY5R BDKRBI OPRKI CXCR3 OPRDl GRPR OPRMl TACRl CCR8 AVPR2 TACR3 AVPRlB CCR3 FY SSTRl MC5R CXCR4 C3AR1 TSHR ELA3A CCKBR NPY6R
NPY2R FPRLl PPYRl CCKAR FSHR GALR2 TRHR TACR2 FPRL2 SSTR2 C5R1 CCRlO GALRl GPR77 GHSR MC3R GALR3 ITGA7 GIT2 FYN ITGAX CDC42
CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl
TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3
PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl PHGDHLl PTGDR GPR85 OR5V1 Rgr P2RY13 LTB4R HTR7 GPR75 ADORA2B ADORA3 GPR39
AD0RA2A HTR2C ADRAlA GPR82 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Peptidoglycan biosynthesis Peptidoglycan biosynthesis GLUL ATP8A1 GNB2L1 GALT EDNRB
EDNRA CCRl FPRl AGTRl MClR BDKRB2CX3CR1 BLRl AVPR1ACCR7 OPRLl OXTR NTSR2 CXCR6 CCR2 CCR6 CCR5 IL8RB LHCGR AGTR2 NMBR NTSRl BRS3 NPY5R BDKRBI OPRKI CXCR3 OPRDl GRPR OPRMl TACRl CCR8 AVPR2 TACR3 AVPRlB CCR3 FY SSTRl MC5R CXCR4 C3AR1 TSHR ELA3A CCKBR
NPY6R NPY2R FPRLl PPYRl CCKAR FSHR GALR2 TRHR GNRHR TACR2 FPRL2 SSTR2 C5R1 CCRlO GALRl GPR77 GHSR MC3R TAC4 GALR3 ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 ROCK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3
TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2
CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl
PPP3CC GNAI l GPR161 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl
PHGDHLl PTGDR GPR85 OR5V1 Rgr P2RY13 LTB4R HTR7 GPR75 ADORA2B
AD0RA3 GPR39 AD0RA2A HTR2C ADRAlA GPR82 TBXA2RGNG7
ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4 Phenylalanine metabolism Phenylalanine metabolism TAT PRDX5 MAOB ALDH3B1 GOTl GOT2 PRDX6 PRDX2 ALDH1A3 ABPl MPO MAOA A0C3 ALDH3B2
DDC ALDH3A1 A0C2 PRDXl LPO OPRKl CXCR3 OPRDl CCR2 GRPR
OPRMl AGTRl TACRl CCR8 AVPR2 TACR3 AVPRlB CCR3 FY SSTRl MC5R
CXCR4 C3AR1 TSHR ELA3A ATP8A1 CCKBR NPY6R NPY2R FPRLl PPYRl CCKAR FSHR GALR2 TRHR CXCR6 GNRHR TACR2 FPRL2 SSTR2 LHCGR EDNRA BLRl C5R1 CCRlO GALRl GPR77 GHSR MC3R GNB2L1 AGTR2 GALT TAC4 CCR7
GALR3 ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2 RAC2 PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGCl 7301 ITGA9 ITGA2 SDCCAG8
ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41
ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 GPR24 CYSLTRl CHRMl GPR92
GPRlO CMKORl PHGDHLl PTGDR GPR85 OR5V1 Rgr P2RY13 LTB4R HTR7 GPR75 ADORA2B ADORA3 GPR39 ADORA2A HTR2C ADRAlA
GPR82 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH
KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D
CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Phenylalanine_tyrosine and tryptophan biosynthesis Phenylalanine_tyrosine and tryptophan biosynthesis
TAT GOTl G0T2 ENOl ENO2 SNRPF ENO3 PAH YARS MAOA A0C3 ALDH3B2 DDC ALDH3A1 ALDH3B1 AOC2 PRDXl LPO PRDX2
ALDH1A3 PRDX5 PRDX6 MAOB OPRKl CXCR3 OPRDl CCR2 GRPR OPRMl AGTRl TACRl CCR8 AVPR2 TACR3 AVPRlB CCR3 FY SSTRl MC5R CXCR4
C3AR1 TSHR ELA3A ATP8A1 CCKBR NPY6R NPY2R FPRLl PPYRl CCKAR FSHR GALR2 TRHR CXCR6 GNRHR TACR2 FPRL2 SSTR2 LHCGR EDNRA BLRl C5R1 CCRlO GALRl GPR77 GHSR MC3R GNB2L1 AGTR2 GALT TAC4 CCR7 GALR3 ITGA7 GIT2 FYN ITGAX CDC42 CAPN9 CAPN3 ITGB8 R0CK2 ITGB3 SORBSl PXN ITGB4 ITGBl CAVl AKT3 SOSl ROCKl SRC ITGAL MAP2K2RAC2
PAK3 ITGA8 SNAPC5 SHCl CAPN2 GRB2 ITGA6 PAK4 MAP2K3ZYX ITGA2B CAPN6 VAV3 TNSl CAPNlO PAK6 ITGAI l BCARl PDPKl FLJ14825 RAPGEFl
VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 TAFlO PAK2 ITGB2 MAPK10CAPN7 EPHAl ITGA4 KIAA0470 LOC441708 MAPK7
AKAP8L PRKARlA PRKD3 PDElA GNAl 4 PDE4D WDR41 ITPRl PDE8A CALMl
PPP3CC GNAI l GPR161 GPR24 CYSLTRl CHRMl GPR92 GPRlO CMKORl
PHGDHLl PTGDR GPR85 OR5V1 Rgr P2RY13 LTB4R HTR7 GPR75 AD0RA2B
AD0RA3 GPR39 ADORA2A HTR2C ADRAlA GPR82 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB
CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4 Phosphatidylinositol signaling system Phosphatidylinositol signaling system PIP5K2BDGKH DGKB
PIK3C2A ITPKB DGKE INPP5A CDKLl PRKCBl CDC2L5 PRKCA PLCG2 INPP4B
DGKG NEKl PRKCZ RAFl CDIPT CSNK2B INPPLl PRKACB PLCGl INPPl
PRKACA IMPAl PAK4 DGKA OCRL CSNK2A2 PLCB4 ACVRl PLCB2
PIM2 PIK3CA PIK3C2BINPP4A BMPRlA PLK3 PLCDl ACVRIBCDSI ITPKA CSNK2A1 PRKCG MAP3K10 PIK3CG PCTK2 TGFBRl CDKL2 PIK4CA PRKGl
AKTl PRKACG PCTKl DGKZ DGKQ DGKD AURKB BMPR2 ACVRLl NEK3
PLCBl PIK3CB CDS2 PLCB3 LOC375133 CLKl PIK3C2G COL4A3BP
SERPINDl CAPNlO TNSl SRC SORBSl AKT3 ITGAI l GRB2 BCARl VAV3
PDPKl GIT2 FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2
CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPK10MAP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA
GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5 GNBl PRKCQ RGSl 7 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4
ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4
Photosynthesis Photosynthesis ATP6V1C2 ATP6V1B1 ATP6V0C ATP6V0A1
ATP5O ATP6V0B ATP6V0E ATP6V1B2 ATP6V1F ATP6V1A ATP6V1C1 ATP6AP1 FDXR ATP6V1E1 ATP6V1G1 ATP6V1D
ATP6V0D1 ATP6V1G2 ATP5E ATP6V0A4 ATP6V1H ATP6V1G3
PLCB4 ACVRl PLCB2 PIM2 PIK3CA PIK3C2BINPP4A PLCG2 BMPRlA PLK3
PLCDl ACVR1BINPP4B CDSl ITPKA CSNK2A1 PRKCG MAP3K10 PIK3CG
DGKG PCTK2 PRKCA TGFBRl CDKL2 PIK4CA PRKGl AKTl PRKACG PCTKl CDC2L5 DGKE DGKZ DGKQ CDKLl PRKCBl DGKD OCRL AURKB BMPR2 ACVRLl
NEKl NEK3 DGKA PLCBl PIK3CB CDS2 PIK3C2A PLCB3 LOC375133 CLKl PIK3C2G PAK4 PRKACA DGKB PLCGl COL4A3BP PRKCZ
CSNK2A2 SERPINDl ITPKB PRKACB RAFl CAPNlO TNSl SRC
SORBSl AKT3 ITGAI l GRB2 BCARl VAV3 PDPKl GIT2 FLJ14825 RAPGEFl
VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKl 0MAP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6
MAPK7 AKAP8L PRKARlA PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A
CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2
ADORA2A HTR2C CCR7 ADRAlA EDNRΛ GPR82 GALR3 TBXA2RGNG7
ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Porphyrin and chlorophyll metabolism Porphyrin and chlorophyll metabolism CP UROS EPRS
BLVRB GUSB FECH HMOXl HCCS BLVRA CPOX UGTl A9 PPOX UGT1A6 UGT2B4 UGTlAl UGT2B15 UGTl A3 UROD HMOX2 ALAD UGT1A8 HPS3 PLCB2 PIM2 PIK3CA PIK3C2BINPP4A PLCG2 BMPRlA PLK3 PLCDl ACVR1BINPP4B CDSl
ITPKA CSNK2A1 PRKCG MAP3K10 PIK3CG DGKG PCTK2 PRKCA TGFBRl
CDKL2 PIK4CA PRKGl AKTl PRKACG PCTKl CDC2L5 DGKE DGKZ DGKQ
CDKLl PRKCBl DGKD OCRL AURKB BMPR2 ACVRLl NEKl NEK3 DGKA PLCBl PIK3CB CDS2 PIK3C2A PLCB3 LOC375133 CLKl PIK3C2G PAK4 PRKACA DGKB PLCGl COL4A3BP PRKCZ CSNK2A2 SERPINDl
ITPKB PRKACB RAFl CAPNlO TNSl SRC SORBSl AKT3 ITGAI l GRB2
BCARl VAV3 PDPKl GIT2 FLJ14825 RAPGEFl VAV2 CAPN5 PAKl
MGC 17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3 FLJ40125 SEPPl
RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPK10MAP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8
FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8L PRKARlA
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3 CAMK2B RGS 14 GJA4
Propanoate metabolism Propanoate metabolism ACATl SDS STAGl ACACA LDHA
LDHB ECHSl ALDH2 ALDH3A2 ACADM MUT PCCA C14orf45 ALDH6A1
EHHADH ABAT ALDH 1A2 LDHC HADHA ALDHlBl ALDHlAl
PCCB SUCLGl ACSS2 PIK3CA PIK3C2BINPP4A PLCG2 BMPRlA PLK3 PLCDl ACVR1BINPP4B CDSl ITPKA CSNK2A1 PRKCG MAP3K10 PIK3CG DGKG
PCTK2 PRKCA TGFBRl CDKL2 PIK4CA PRKGl AKTl PRKACG PCTKl CDC2L5
DGKE DGKZ DGKQ CDKLl PRKCBl DGKD OCRL AURKB BMPR2 PLCB2 ACVRLl NEKl NEK3 DGKA PLCBl PIK3CB CDS2 PIK3C2A PLCB3 LOC375133
CLKl PIK3C2G PAK4 PRKACA DGKB PLCGl COL4A3BP PRKCZ CSNK2A2 SERPINDl ITPKB PRKACB RAFl CAPNlO TNSl SRC
SORBSl AKT3 ITGAI l GRB2 BCARl VA V3 PDPKl GIT2 FLJ14825 RAPGEFl
VA V2 CAPN5 PAKl MGCl 7301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3
FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKl 0MAP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6
MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A
CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO
GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7
ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2
WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD
RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4 Prostaglandin and leukotriene metabolism Prostaglandin and leukotriene metabolism PTGS2
PRDX5 TBXASl PRDX6 PRDX2 PLA2G2A MPO ALOX5 PLA2G6 PTGSl CBR3 PLA2G5 PLA2G1B CYP4F3 PGDS GGTl ALOX12 ALOX 15 PTGIS PRDXl LTA4H
CYP4F2 LPO PTGDS GGT2 PTGES2 PLA2G3 PRKCA TGFBRl CDKL2 PIK4CA PRKGl AKTl PRKACG PCTKl CDC2L5 DGKE DGKZ DGKQ CDKLl PRKCBl DGKD
ACVRIBOCRL INPP4A AURKB BMPR2 PLCB2 ACVRLl NEKl NEK3 DGKA PLCBl CSNK2A1 PIK3CB CDS2 PIK3C2A PLCB3 LOC375133 BMPRlA
CLKl PIK3C2G PAK4 PRKACA DGKB PLCGl COL4A3BP PRKCZ
PCTK2 INPP4B CSNK2A2 CDSl SERPINDl ITPKB PRKACB DGKG
PRKCG RAFl CAPNlO TNSl SRC SORBSl AKT3 ITGAI l GRB2 BCARl VAV3 PDPKl GIT2 FLJ14825 RAPGEFl VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCC AG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2
CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKlO M AP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA
GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR
GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA
GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4
ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B
RGS14 GJA4
Prostaglandin_synthesis_regulation Prostaglandin_synthesis_regulation PTGS2 PTGFR PTGIR
ANXA8 EDNl TBXASl ANX A5 ANXA6 ANXAl ANXA4 ANXA2 HPGD HSDl 1B2 EDNRB CYPI lAl EDNRA PTGER4 PTGSl HSDI lBl PRL SCGBlAl
PTGER2 PTGERl PTGIS ANXA3 PLA2G4A ANXA2P1 PTGDS PTGDR S100A6
PRKCA TGFBRl CDKL2 PIK4CA PRKGl AKTl PRKACG PCTKl CDC2L5 DGKE
DGKZ DGKQ CDKLl PRKCBl DGKD ACVRIBOCRL INPP4A AURKB BMPR2 PLCB2 ACVRLl NEKl NEK3 DGKA PLCBl CSNK2A1 PIK3CB CDS2 PIK3C2A PLCB3 LOC375133 BMPRlA CLKl PIK3C2G PAK4 PRKACA
DGKB PLCGl COL4A3BP PRKCZ PCTK2 INPP4B CSNK2A2 CDSl SERPINDl
ITPKB PRKACB DGKG PRKCG RAFl CAPNlO TNSl SRC SORBSl AKT3
ITGAI l GRB2 BCARl VAV3 PDPKl GIT2 FLJ14825 RAPGEFl VAV2
CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3 FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 ROCKl
TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKlO M AP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B
ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA GPR82
GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5 GNBl PRKCQ
RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 SFN CACNB3CAMK2B RGS14
GJA4
Proteasome Proteasome UBElL PSMDlO UBEl PSMD6 PSMA5 PSMD5 UBE2D3
RPS27A PSMB2 UBB PSMB7 PSMEl PSMD8 PSMD2 H2AFZ PSMBl PSMD4 HLA-E RPNl PSMC2 PSMA7 PSMDl PSMD13 PSMC4 PSMC3 PSMA2 UBE2D2 PSMD3 PSMB3 PSMA3 PSMAl PSMD7 PSME2 PSMB4 PSMD12 PSMBlO PSM A4 PSMCl PSMB9 HLA-F
H2AFX INEl PSMD9 RPN2 HLA-B PSMDI l PSMB5 PSMA6 HLA-C PSMB6 UBC PSMB8 PSMC5 HLA-G UBE2D1 NEDD4 HLA-A UBA52 NEK6 SLC26A5 FLJ31306
LOC253039 LOC388720 INPP4B TGFBRl CSNK2A2 BMPR2 PIK3C2A
CDSl COL4A3BP DGKQ ACVRLl INPP4A PRKCBl CDS2 CDC2L5 SERPINDl BMPRlA ITPKB CDKLl PRKACB DGKG PRKCG PCTK2 CSNK2A1
AURKB DGKZ NEK3 PLCBl RAFl PAK4 CAPNlO TNSl SRC SORBSl AKT3 ITGAI l GRB2 BCARl VA V3 PDPKl GIT2 FLJ14825 RAPGEFl VA V2
CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3 FLJ40125
SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKl 0MAP2K2ITGA8 PAK6 CAPN7 EPHAl
ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8LPRKAR1A
PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB CACNAlE GNAQ YWHAH KCNJ5
GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4
GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3
CAMK2B RGS14 GJA4 Proteasome_Degradation Proteasome Degradation UBElL PSMDlO UBEl PSMD6 PSM A5
PSMD5 UBE2D3 RPS27A PSMB2 UBB PSMB7 PSMEl PSMD8 PSMD2 H2AFZ PSMBl PSMD4 HLA-E RPNl PSMC2 PSMA7 PSMDl PSMD13 PSMC4 PSMC3 PSMA2 UBE2D2 PSMD3 PSMB3 PSMA3 PSMAl PSMD7 PSME2 PSMB4 PSMD12 PSMBlO PSM A4 PSMCl PSMB9 HLA-F H2AFX INEl PSMD9 RPN2 HLA-B PSMDI l PSMB5 PSMA6 HLA-C PSMB6 UBC PSMB8 PSMC5 HLA-G UBE2D1 NEDD4 HLA-A UBA52 NEK6 SLC26A5
FLJ31306 LOC253039 LOC388720 INPP4B TGFBRl CSNK2A2 BMPR2
PIK3C2A CDSl COL4A3BP DGKQ ACVRLl INPP4A PRKCBl CDS2 CDC2L5
SERPINDl BMPRlA ITPKB CDKLl PRKACB DGKG PRKCG PCTK2
CSNK2A1 AURKB DGKZ NEK3 PLCBl RAFl PAK4 CAPNlO TNSl SRC SORBSl AKT3 ITGAI l GRB2 BCARl VAV3 PDPKl GIT2 FLJ14825 RAPGEFl
VAV2 CAPN5 PAKl MGC17301 ITGA9 ITGA2 SOSl SDCCAG8 ITGA3
FLJ40125 SEPPl RAPlB MYLK2 CAPNl TLNl DOCKl PTK2 ILK
DKFZP564G2022 ROCKl TAFlO CAPN3 PAK3 PAK2 ITGB2 MAPKl OM AP2K2ITGA8 PAK6 CAPN7 EPHAl ITGB8 FYN ITGA4 KIAA0470 LOC441708 ITGA6 MAPK7 AKAP8LPRKAR1A PRKD3 PDElA GNA14 PDE4D WDR41 ITPRl PDE8A
CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO
GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2
AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 CACNAlB
CACNAlE GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2
WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJA4
Purine metabolism Purine metabolism PDE8A PDE5A CANTl PDE4D ADCY7 POLR2B ATP5H NT5C PDE6B POLA ATP5J2 PDElA POLE HPRTl FHIT GDA PDE9A ADK
PAICS POLD2 PKM2 NME2 ATP5B RRMl NMEl NP RRM2 IMPDH2 ADSL
POLR2G ATP5J POLR2L AKl POLR2K POLR2A APRT DCK POLG PRPS2 POLDl POLB POLR2D PDE4B POLRMT DGUOK GUCYl B3 ATP5D IMPDHl NPR2
ADA NPRl PDE4A ECGFl ENPPl ATP5C1 AK2 AMPDl GUCY2C PDE4C ADCY8 GUCY1A2 ATP5I ENTPD2 ATP5G3 ENTPDl POLQ PKLR GUCY2D
AMPD3 GUCY2FPRPS1 ATIC ATP5G2 ATP5G1 POLR2C ITPA ADCY6 POLR2H ADCY3 PPAT POLR2F GART PDE6G XDH PDE6C ATP5F1 AMPD2 POLR2J POLR2I ADCY2 ADCYl PFAS ATP5A1 POLR2E DOK4 GMPS SAC PRPSlLl HA-I NUDT2
RBAK AK5 NT5M POLRlB ALLC ADSS GUCY1A3 ENPP3 ADCY5 ADCY4 IGFBP7 LOC440836 SRP72 PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl
ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470
LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A
PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 AD0RA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4
Pyrimidine metabolism Pyrimidine metabolism CANTl TKl DPYD TYMS POLR2B
NT5C POLA POLE CAD POLD2 TXNRD1NME2 RRMl DCTD NMEl NP RRM2 POLR2G POLR2L CTPS POLR2K UMPS POLR2A DCK POLG POLDl POLB POLR2D POLRMT AK3L1 ECGFl CDA DPYS ENTPDl POLQ DUT POLR2C
ITPA POLR2H POLR2F UCK2 P0LR2J P0LR2I DHODH POLR2E DOK4 HA-I NUDT2 CTPS2 RBAK NT5M POLRlB IGFBP7 LOC440836 ATP5G1 ADCY6 ADCY3 PPAT
PRPSl AMPD3 ATP5I DGUOK GART PDE6G ATP5H ADSL XDH PDE6B PKLR PDE4D PDE6C PDE4B PDE4A GUCY 1B3 ATP5F1 PDE4C AK2 AMPD2 PDE8A ATP5D ADCY2 ADCYl PFAS ATP5C1 PKM2 ATP5A1 APRT NPR2 GMPS SAC
PAICS PRPSlLl ADA AK5 ALLC ADSS GUCY1A3 ENPP3 GDA
PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A PRKD3 GNA14 WDR41 ITPRl CALMl
PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13
LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A
HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2
ANXA6 SFN CACNB3CAMK2B RGS 14 GJA4
Pyruvate metabolism Pyruvate metabolism ACATl PDHAl ME2 ACACA LDHA
GLOl MDHl LDHB PKM2 AKRlBl GRHPR ALDH2 ALDH3A2 MEl PC ME3 HAGH ACYPl ACYP2 ALDH1A2 LDHC PKLR PCKl ADH5 PDHB
MDH2 DLD ALDHlBl DLAT ALDHlAl PDHA2 HAGHL LDHD ACSS2
MAP3K15 POLR2E POLR2D DOK4 UMPS POLE POLD2 POLR2C POLR2A ECGFl
HA-I POLG TYMS NUDT2 CTPS2 RBAK POLQ NT5M POLRlB CANTl AK3L1 IGFBP7 POLR2F RRMl POLB LOC440836 TKl ATP5G1 ITPA ADCY6 POLR2H ADCY3 PPAT PRPSl ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H
ADSL XDH PDE6B PDE4D PDE6C PDE4B PDE4A GUCY1B3 POLR2L ATP5F1
PDE4C AK2 AMPD2 PDE8A P0LR2J POLR2I ATP5D ADCY2 ADCYl PFAS ATP5C1 ATP5A1 APRT NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC
ADSS GUCYl A3 ENPP3 GDA PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl
ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470
LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A
PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC GNAI l GPRl 61 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 AD0RA2B AD0RA3
GPR39 SSTR2 AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4
RNA polymerase RNA polymerase POLR2B POLR2G P0LR2L POLR2K POLR2A POLR2D POLRMT
POLR2C POLR2H POLR2F POLR2J POLR2I P0LR2E D0K4 HA-I POLRlB IGFBP7 ADH5 PDHB MDH2 DLD ME2 ALDHlBl PKLR ALDH3A2 DLAT MEl ACACA ALDHlAl LDHB PKM2 PDHA2 GRHPR HAGHL LDHD ME3 ACSS2
MDHl MAP3K15 PDHAl UMPS POLE POLD2 ECGFl POLG TYMS NUDT2
CTPS2 RBAK POLQ NT5M CANTl AK3L1 RRMl POLB LOC440836 TKl
ATP5G1 ITPA ADCY6 ADCY3 PPAT PRPSl ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H ADSL XDH PDE6B PDE4D PDE6C PDE4B PDE4A GUCY1B3 ATP5F1 PDE4C AK2 AMPD2 PDE8A ATP5D ADCY2 ADCYl PFAS ATP5C1 ATP5A1
APRT NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC ADSS
GUCYl A3 ENPP3 GDA PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72
PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A PRKD3 GNA14
WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1
SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB
CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16
SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4 RNA_transcription_Reactome RNA_transcription_Reactome TAF5 P0LR2B POLR3B
MNATl MGC9850 TAF7 ILK TAF9 ERCC3 POLR2G GTF2H1 POLR2K GTF2A2
GTF2E2 P0LR2A TBP TAF6 GTF2H4 CCNH GTF2E1 TAF13 GTF2B POLR3D POLR2C POLR2H TAF12 P0LR2F GTF2F2 CDK7 POLR2J P0LR2I POLR2E D0K4 HA-I POLR3E POLR3K POLRlB GTF2H2 POLRl A VARSL IGFBP7 POLR3H TAFlO UMPS POLE POLD2 ECGFl POLG TYMS NUDT2 CTPS2 RBAK POLQ NT5M CANTl AK3L1 RRMl
POLB LOC440836 TKl POLR2D ATP5G1 ITPA ADCY6 ADCY3 PPAT PRPSl
ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H ADSL XDH PDE6B PKLR PDE4D PDE6C PDE4B PDE4A GUCY 1B3 POLR2L ATP5F1 PDE4C AK2
AMPD2 PDE8A ATP5D ADCY2 ADCYl PFAS ATP5C1 PKM2 ATP5A1 APRT NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC ADSS GUCY1A3
ENPP3 GDA PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK §4 NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708 RAPGEFl
PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A PRKD3 GNA14 WDR41 ITPRl
CALMl PPP3CC GNAI l GPRl 61 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2
AD0RA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7
RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJA4
Reductive carboxylate cycle (CO2 fixation) Reductive carboxylate cycle (CO2 fixation) IDHl
ACO2 MDHl FH ACOl MDH2 IDH2 GTF2H1 POLR2K GTF2A2 GTF2E2 POLR2A
TBP MNATl TAF6 GTF2H4 TAF9 CCNH GTF2E1 TAF13 GTF2B POLR3D POLR2C POLR2H TAF12 P0LR2F GTF2F2 TAF5 CDK7 P0LR2J POLR2I POLR2E DOK4 ERCC3
HA-I POLR3E POLR3K POLR3B POLRlB GTF2H2 POLRl A MGC9850 VARSL IGFBP7
P0LR3H ILK TAFlO UMPS POLE POLD2 ECGFl POLG TYMS NUDT2 CTPS2 RBAK POLQ NT5M CANTl AK3L1 RRMl POLB LOC440836 TKl POLR2D
ATP5G1 ITPA ADCY6 ADCY3 PPAT PRPSl ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H ADSL XDH PDE6B PKLR PDE4D PDE6C PDE4B PDE4A
GUCY1B3 POLR2L ATP5F1 PDE4C AK2 AMPD2 PDE8A ATP5D ADCY2 ADCYl
PFAS ATP5C1 PKM2 ATP5A1 APRT NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC ADSS GUCY1A3 ENPP3 GDA PDE5A ATP5G3 ADCY5
ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8
KIAA0470 LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8L
PRKARlA PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2
GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR 0R5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH
KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A CAMK2D
CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Retinol metabolism Retinol metabolism BCMOl ACO2 MDHl IDHl FH ACOl MDH2
IDH2 GTF2H1 POLR2K GTF2A2 GTF2E2 POLR2A TBP MNATl TAF6 GTF2H4 TAF9 CCNH GTF2E1 TAF13 GTF2B POLR3D POLR2C POLR2H TAF12 POLR2F GTF2F2 TAF5 CDK7 POLR2J POLR2I POLR2E DOK4 ERCC3 HA-I POLR3E POLR3K POLR3B POLRlB GTF2H2 POLRlA MGC9850 VARSL IGFBP7 POLR3H ILK TAFlO UMPS POLE
P0LD2 ECGFl POLG TYMS NUDT2 CTPS2 RBAK POLQ NT5M CANTl AK3L1 RRMl POLB LOC440836 TKl POLR2D ATP5G1 ITPA ADCY6 ADCY3 PPAT
PRPSl ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H ADSL XDH PDE6B PKLR PDE4D PDE6C PDE4B PDE4A GUCY1B3 POLR2L ATP5F1 PDE4C AK2 AMPD2 PDE8A ATP5D ADCY2 ADCYl PFAS ATP5C1 PKM2 ATP5A1 APRT
NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC ADSS GUCY1A3
ENPP3 GDA PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708 RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8LPRKAR1A PRKD3 GNA14 WDR41 ITPRl
CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO
GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B AD0RA3 GPR39 SSTR2
ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJA4
Riboflavin metabolism Riboflavin metabolism TYR ACP5 ACP2 RFK ACPP ENPPl FLADl ENPP3 DDB2 ACPT MNATl TAF6 GTF2H4 TAF9 CCNH GTF2E1
TAF 13 GTF2B POLR3D POLR2C POLR2H TAF12 POLR2F GTF2F2 TAF5 CDK7 P0LR2J P0LR2I POLR2E DOK4 ERCC3 POLR2A HA-1 POLR3E POLR3K POLR3B POLRlB GTF2H2 POLRlA MGC9850 VARSL GTF2A2 IGFBP7 POLR3H ILK TAFlO GTF2H1 UMPS
POLE POLD2 ECGFl POLG TYMS NUDT2 CTPS2 RBAK POLQ NT5M CANTl AK3L1 RRMl POLB LOC440836 TKl POLR2D ATP5G1 ITPA ADCY6 ADCY3
PPAT PRPSl ENTPDl AMPD3 ATP5I DGUOK RRM2 GART PDE6G ATP5H ADSL XDH PDE6B PKLR PDE4D PDE6C PDE4B PDE4A GUCY 1B3 POLR2L ATP5F1
PDE4C AK2 AMPD2 PDE8A ATP5D ADCY2 ADCYl PFAS ATP5C1 PKM2 ATP5A1 APRT NPR2 GMPS SAC PAICS PRPSlLl ADA AK5 ALLC ADSS
GUCYl A3 GDA PDE5A ATP5G3 ADCY5 ENTPD2 ADCY4 PDElA SRP72 PDE9A ADK NPRl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl
AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708
RAPGEFl PDPKl ITGA6 PAK4 MAPK7 AKAP8L PRKARlA PRKD3 GNA14
WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl
GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3
GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3
TBXA2RGNG7 RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14
GJA4
Ribosomal_Proteins Ribosomal_Proteins PIGK RPS24 TSPAN9 RPL5 RPS6KA2
RPS9 RPS20 LOC133957 ANK2 RPL4 RPS15 RPS4Y1 RPL13 RPL37 RPS6KA3
RPLlO SCDRlO RPL35 RPL28 RPLI l RPL21 RPL24 RPS27A RPS13 FAU RPL18 RPL27 RPL34 RPL19 RPSI l RPL9 RPL6 RPL17 RPL30 RPL14 RPS6 RPS7
RPLl 2 RPS25 FLJ20294 RPS3A UBB RPL32 RPLl 3 A RPL7 RPS27 RPLPl
RPSlO RPL29 RPS21 RPS8 RPLl 8 A RPL23 RPLP2 RPS23 RPS4X RPL8 TBC 1D8 RPL31 RPLPO RPS18 RPS29 RPL3 RPS16 RPL41 RPS17 RPL38 RPS19 RPL27A RPS2 RPS6KA1 MRPL19 RPS6KB2 RPS6KB1 IL6ST RPL3L DGKI CDRl RPS 14 RPS3 RPL39 RPL22 ANKRD47 RPS28 UBC B3GALT4
LOC388344 LOC402057 LOC440055 RPL35A FAM69ARPSA EVIl LOC442209
LOC285053 LOC387753 LOC388401 LOC136321 LOC158104 LOC148430
RPL7A RPS26 RPL36 RPS6KA6 RPL15 UBA52 LOC391126 TBClDlOC
KIAA1394 LOC133748 LOC388720 LOC401551 XDH DGUOK PDElA PDE4D POLR2D ENPP3 AMPD3 PPAT PDE8A GART NPRl CANTl PTK2 PAK6
CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl AKT3 ITGB8 FYN GIT2 ITGA4 SDCCAG8 KIAA0470 LOC441708 RAPGEFl PDPKl ITGA6
PAK4 MAPK7 AKAP8LPRKAR1A PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC
GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7
NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C
CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE
KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB
CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJA4
SlP_Signaling SlP_Signaling MAPKl SDCCAG8 ASAHl C9orf47 GNAI2 GNAI3
DNMTl PLCB2 PIK3C2BEDG1 MAPK4 MAPK12MAPK6 AKTl MAPK7 SERPINHl EDG5 SPHK2 PLCBl MAPK3 AKT3 PLCB3 SPHKl EDG8 RACGAPl KIAA0470 RPL29 RPS21 RPS8 RPLl 8 A RPL23 RPLP2 RPS23 RPS4X RPL8 RPL5 RPS20
TBC1D8 RPL31 RPLPO RPS18 RPS29 RPL4 RPL3 RPS6 RPS3A RPS16 RPL41 RPS17 RPS4Y1 RPL38 RPS19 ANK2 RPL27A RPS2 RPS6KA1 MRPL19 RPS6KB2
RPS6KA3 RPS6KB1 IL6ST RPS6KA2 RPL3L DGKI CDRl RPS14
RPS3 RPL39 RPL22 ANKRD47 RPS28 RPLl 3 UBC PIGK B3GALT4 RPL13A RPSlO RPL7 LOC388344 RPL17 LOC402057 RPL28 LOC440055
RPL14 RPL35A FAM69ARPSA RPS7 EVIl RPL24 RPL12 RPS9 RPL18 LOC442209 LOC285053 LOC387753 LOC388401 UBB LOC136321 LOC158104
LOC148430 RPL7A RPS26 RPL36 RPS6KA6 TSPAN9 RPL15 UBA52 RPLlO
LOC391126 RPL37 LOC133957 RPL30 TBClDlOC SCDRlO KIAAl 394 LOC133748 RPS27 RPL32 FLJ20294 LOC388720 LOC401551 RPLPl
RPS27A XDH DGUOK PDElA PDE4D POLR2D ENPP3 AMPD3 PPAT PDE8A GART NPRl CANTl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl SOSl ITGA8 SORBSl ITGB8 FYN GIT2 ITGA4 LOC441708 RAPGEFl PDPKl ITGA6 PAK4
AKAP8LPRKAR1A PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT CMKORl PHGDHLl
PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A HTR2C CCR7 ADRAlA
EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS 17 CAMK2G ATP2A2 WDR42A
CAMK2D CAMK4 GRK4 ATP2B3 RGS 16 SLC8A3 CACNAlD RYR2 GNG2 ANXA6 SFN CACNB3CAMK2B RGS14 GJA4
Selenoamino acid metabolism Selenoamino acid metabolism AHCY MARS MATlA
CTH GGTl SEPHSl GGT2 MAT2B SCLY SERPINHl MAPKl EDG5 SPHK2
PLCB2 ASAHl PLCBl MAPK3 AKT3 PLCB3 SPHKl EDG8 RACGAPl SDCCAG8 C9orf47 KIAA0470 MAPK7 RPL29 RPS21 RPS8 RPLl 8A RPL23 RPLP2 RPS23
RPS4X RPL8 RPL5 RPS20 TBC1D8 RPL31 RPLPO RPS 18 RPS29 RPL4 RPL3
RPS6 RPS3A RPS16 RPL41 RPS17 RPS4Y1 RPL38 RPS19 ANK2 RPL27A RPS2
RPS6KA1 MRPL19 RPS6KB2 RPS6KA3 RPS6KB1 IL6ST RPS6KA2
RPL3L DGKI CDRl RPS 14 RPS3 RPL39 RPL22 ANKRD47 RPS28 RPLl 3 UBC PIGK B3GALT4 RPL13A RPSlO RPL7 LOC388344 RPL17 LOC402057
RPL28 LOC440055 RPL14 RPL35A FAM69ARPSA RPS7 EVIl RPL24 RPL12
RPS9 RPLl 8 LOC442209 LOC285053 LOC387753 LOC388401 UBB
LOC136321 LOC158104 LOC148430 RPL7A RPS26 RPL36 RPS6KA6
TSPAN9 RPL15 UBA52 RPLlO LOC391126 RPL37 LOC133957 RPL30 TBClDlOC SCDRlO KIAA1394 LOC133748 RPS27 RPL32 FLJ20294 LOC388720
LOC401551 RPLPl RPS27A XDH DGUOK PDElA PDE4D POLR2D ENPP3 AMPD3
PPAT PDE8A GART NPRl CANTl PTK2 PAK6 CAPN7 ITGA9 EPHAl DOCKl
SOSl ITGA8 SORBSl ITGB8 FYN GIT2 ITGA4 LOC441708 RAPGEFl
PDPKl ITGA6 PAK4 AKAP8L PRKARlA PRKD3 GNA14 WDR41 ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92 GPRlO GALT
CMKORl PHGDHLl PTGDR GPR85 CCKBR OR5V1 SSTRl Rgr P2RY13
LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2 ADORA2A
HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 TBXA2RGNG7 ADCYl RGS3
PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB CACNAlB CACNAlE PRKCG GNAQ YWHAH KCNJ5 GNBl PRKCQ RGS17 CAMK2G
ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS16 SLC8A3 CACNAlD
RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14 GJ A4
Small_ligand_GPCRs Small_ligand_GPCRs PTGFR PTGIR C9orf47 DNMTl EDG2
EDGl PTGER4 PTAFR EDG6 CNR2 PTGER2 TBXA2RPTGER1 CNRl MTNRlB EDG5 PTGDR MTNRlA ASAHl PLCBl SPHKl AKT3 EDG8 RACGAPl
SDCCAG8 KIAA0470 MAPK7 SPHK2 RPL29 RPS21 RPS8 RPL18A RPL23
RPLP2 RPS23 RPS4X RPL8 RPL5 RPS20 TBC1D8 RPL31 RPLPO RPS18 RPS29
RPL4 RPL3 RPS6 RPS3A RPS16 RPL41 RPS17 RPS4Y1 RPL38 RPS19 ANK2
RPL27A RPS2 RPS6KA1 MRPL19 RPS6KB2 RPS6KA3 RPS6KB1 IL6ST RPS6KA2 RPL3L DGKI CDRl RPS14 RPS3 RPL39 RPL22 ANKRD47
RPS28 RPL13 UBC PIGK B3GALT4 RPL13A RPSlO RPL7 LOC388344
RPLl 7 LOC402057 RPL28 LOC440055 RPL14 RPL35A FAM69ARPSA RPS7
EVIl RPL24 RPL12 RPS9 RPL18 LOC442209 LOC285053 LOC387753
LOC388401 UBB LOC136321 LOC158104 LOC148430 RPL7A RPS26 RPL36 RPS6KA6 TSPAN9 RPL15 UBA52 RPLlO LOC391126 RPL37 LOC133957
RPL30 TBClDlOC SCDRlO KIAA1394 LOC133748 RPS27 RPL32 FLJ20294
LOC388720 LOC401551 RPLPl RPS27A XDH DGUOK PDElA PDE4D POLR2D
ENPP3 AMPD3 PPAT PDE8A GART NPRl CANTl PTK2 PAK6 CAPN7 ITGA9
EPHAl DOCKl SOSl ITGA8 SORBSl ITGB8 FYN GIT2 ITGA4 LOC441708 RAPGEFl PDPKl ITGA6 PAK4 AKAP8L PRKARlA PRKD3 GNA14 WDR41
ITPRl CALMl PPP3CC GNAI l GPR161 FPRL2 GPR24 CYSLTRl CHRMl GPR92
GPRlO GALT CMKORl PHGDHLl GPR85 CCKBR OR5V1 SSTRl Rgr
P2RY13 LTB4R HTR7 NPY6R GPR75 ADORA2B ADORA3 GPR39 SSTR2
ADORA2A HTR2C CCR7 ADRAlA EDNRA GPR82 GALR3 GNG7 ADCYl RGS3 PRKCE KCNJ3 RYR3 PRKCH SLC8A1 ATP2B2 CALM2 ADCY3 PRKACB
CACNAlB CACNAlE PRKCG GNAQ YWHAH KCN J5 GNBl PRKCQ RGS 17
CAMK2G ATP2A2 WDR42A CAMK2D CAMK4 GRK4 ATP2B3 RGS 16
SLC8A3 CACNAlD RYR2 GNG2 ANX A6 SFN CACNB3CAMK2B RGS 14
GJA4 Smooth_muscle_contraction Smooth_muscle_contraction ADMR LGR7 LGR8 SPl GNB5
ATF3 CREBLl RGS7 RGSI l PDE4D ADCY7 ATF2 GNGl 2 RGS5 GNG4 GNG2
CMKORl PRKCBl SLC8A1 GSTOl ATFl LOC440698 PRKCH PRKCA NOSl
RGS6 ITPRl PLCG2 ACTA2 PRKCE GNG7 RGS20 PRKCZ GNBl C 14orf91 PRKARlA
CALM3 CALMl YWHAQ ATF4 GNB2 YWHAH ITPR3 ETS2 JUN IGFBP4 SARAl CNN2 GJAl RGS2 PRKCD GNAQ ITPR2 IGFBP2 PKIG PRKACB PLCGl
PRKACA GRK6 ADM RGSl ARRB2 PRKAR2B PDE4B RGS3 IGFBP6
ACTAl RCP9 CNNl EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 ADCY9 PKIA
GABPB2 PRKAR2A RAMPl ATF5 ILlB PLCDl ACTC MAFF IL6 IGFBPl
RAMP3 RYRl N0S3 CRH RAMP2 PRKDl USP5 GNB3 RYR3 RGS9 ADCY8 OXTR GUCA1BGNG5 GNGTl CALM2 GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A
GRK4 CRHRl YWHAB ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3MYL2 CAMK2B PRKCQ MYL4 IGFBP3 GABPA CALCA RLNl PRKARlB
CAMK2G ADCY2 ADCYl PLCB3 ARRBl MGCl 1266 RGS17 CORIN GNG13
GUCYl A3 GNG3 GNB4 PKIB RGSl 8 GBA2 CAMK2D ADCY5 C6orfl25
ADCY4 MYLK2 Starch and sucrose metabolism Starch and sucrose metabolism G6PC HKl PYGB
GYSl PGMl GUSB GAA HK2 PYGL GBEl AGL UGT1A9 ENPPl PYGM HK3 UGT1A6 UGT2B4 MGAM UGTlAl UGT2B15 GPI AMYlA UGT1A3 GCK
GYS2 UGT1A8 ENPP3 AMY2B SLC8A1 PRKCE GNG7 RGS20 PRKCZ GNBl C14orf91 PRKARlA CALM3 CALMl YWHAQ ATF4 GNB2 ACTA2 YWHAH ITPR3 ETS2 JUN GSTOl IGFBP4 SARAl CNN2 GJAl RGS2 PRKCD GNAQ ITPR2 ATF3
IGFBP2 PKIG PRKACB PLCGl PRKACA GRK6 ADM RGSl CREBLl
ARRB2 PRKAR2B PDE4B ITPRl ADCY7 RGS3 IGFBP6 ACTAl RCP9 CNNl
GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2A RAMPl ATF5 ILlB PLCDl ACTC GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH
RGSI l RGS7 RYR3 RGS9 ADCY8 OXTR PRKCA GUCA1BGNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl
YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 MYL2 CAMK2B PRKCQ MYL4 IGFBP3 GABPA RGS6 CALCA RLNl GNG12 PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3 ADMR SPl
ARRBl MGCl 1266 RGS17 CORIN GNG13 GUCYl A3 GNG3 ATFl GNB4
PKIB RGS 18 GB A2 GNG2 CAMK2D ADCY5 C6orfl25 ADCY4 MYLK2 LGR7
Statin_Pathway_PharmGKB Statin Pathway PharmGKB SCARBl LRPl LIPC ABCAl LDLR
HMGCR APOE LPL DGATl APOCl LCAT APOAl APOC2 APOC3 CETP APOA4 CYP7A1 SOATl GNG7 RGS20 PRKCZ GNBl C 14orf9 I PRKARlA CALM3 CALMl
YWHAQ ATF4 GNB2 ACTA2 YWHAH ITPR3 ETS2 JUN GSTOl IGFBP4 SARAl CNN2 GJAl RGS2 PRKCD GNAQ ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl PRKACA GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B
ITPRl ADCY7 RGS3 IGFBP6 ACTAl RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS 19 RGS4 GRK5 PDE4D ADC Y9 PKIA PLCG2 GABPB2 PRKAR2A RAMPl
ATF5 ILlB PLCDl ACTC GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2B ATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3MYL2 CAMK2B
PRKCQ MYL4 IGFBP3 GABPA RGS6 CALCA RLNl GNG12 PRKARlB CAMK2G
CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266 RGS 17
CORIN GNG13 GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2
CAMK2D ADCY5 C6orfl25 ADCY4 MYLK2 LGR7 Steroid_Biosynthesis Steroid_Biosynthesis CYP 17Al HSD17B4 HSD3B1
HSD17B2 HSD17B1 HSD3B2 HSD17B3 F13B HSD17B7 APOE
ABCAl LPL DGATl APOCl LCAT APOAl AP0C2 APOC3 CETP LIPC AP0A4 CYP7A1 SCARBl LDLR SOATl GNG7 RGS20 PRKCZ GNBl C 14orf9 I PRKARlA CALM3 CALMl YWHAQ ATF4 GNB2 ACTA2 YWHAH ITPR3 ETS2 JUN GSTOl IGFBP4 SARAl CNN2 GJAl RGS2 PRKCD GNAQ ITPR2 ATF3 IGFBP2 PKIG
PRKACB PLCGl PRKACA GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B
PDE4B ITPRl ADCY7 RGS3 IGFBP6 ACTAl RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS 19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2A RAMPl ATF5 ILlB PLCDl ACTC GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7
RYR3 RGS9 ADCY8 OXTR PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB
RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3MYL2 CAMK2B PRKCQ MYL4 IGFBP3 GABPA RGS6 CALCA RLNl GNG12 PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266
RGS17 CORIN GNG13 GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2
GNG2 CAMK2D ADCY5 C6orfl25 ADCY4 MYLK2 LGR7
Stilbene_coumarine and lignin biosynthesis Stilbene_coumarine and lignin biosynthesis TYR
PRDX5 PRDX6 PRDX2 MPO PRDXl LPO LPL DGATl APOCl LCAT APOAl APOC2 APOC3 CETP LIPC APOA4 CYP7A1 SCARBl ABCAl LDLR SOATl GNG7
RGS20 PRKCZ GNBl C 14orf91 PRKARlA CALM3 CALMl YWHAQ ATF4 GNB2
ACTA2 YWHAH ITPR3 ETS2 JUN GSTOl IGFBP4 SARAl CNN2 GJAl RGS2 PRKCD GNAQ ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl PRKACA
GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl ADCY7 RGS3 IGFBP6 ACTAl RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5
PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2 A RAMPl ATF5 ILlB PLCDl ACTC GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2
PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR
PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2
OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3MYL2 CAMK2B PRKCQ MYL4
IGFBP3 GABPA RGS6 CALCA RLNl GNG12 PRKARlB CAMK2G CMKORl
ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266 RGS17 CORIN GNG13
GUCYl A3 GNG3 ATFl GNB4 PKIB RGS 18 GB A2 GNG2 CAMK2D
ADCY5 C6orfl25 ADCY4 MYLK2 LGR7 Streptomycin biosynthesis Streptomycin biosynthesis HKl PGMl HK2 IMPAl HK3
GCK MPO TYR PRDXl LPO PRDX2 PRDX5 PRDX6 LPL DGATl APOCl
LCAT APOAl APOC2 APOC3 CETP LIPC AP0A4 CYP7A1 SCARBl ABCAl LDLR
SOATl GNG7 RGS20 PRKCZ GNBl C 14orf91 PRKARlA CALM3 CALMl YWHAQ
ATF4 GNB2 ACTA2 YWHAH ITPR3 ETS2 JUN GSTOl IGFBP4 SARAl CNN2
GGJJAAll RRGGSS22 PPRRKKCCDD GGNNAAQQ IITTPPRR22 ATF3 IGFBP2 PKIG PRKACB PLCGl
PRKACA GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl
ADCY7 r RGS3 IGFBP6 ACTAl RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19
RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2PRKAR2A RAMPl ATF5
ILlB PLCDl ACTC GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3
CCRRHH RRAAMMPP22 PPRRKKDDll UUSSPP55 GGNNBB33 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9
ADCY8 OXTR PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3
DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2
FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3MYL2 CAMK2B
PRKCQ MYL4 IGFBP3 GABPA RGS6 CALCA RLNl GNG12 PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266 RGS17
CORIN GNG13 GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2
CAMK2D ADCY5 C6orfl25 ADCY4 MYLK2 LGR7
Srriated_muscle_contraction Striated_muscle_contraction C9orf97 VIM TTN TPMl TPM4
TNNT2 ACTA2 TPM3 TNNT3 ACTN4 MYL9 DES TMODl ACTN2 ACTAl DMD TPM2 MYH7 NEB ACTC TNNIl TNNC2 MYL3 MYOMl TNNI3 TCAP MYH3
TNNI2 MYBPC2 MYH8 ACTN3 MYBPC3 MYL2 MYLl MYL4 TNNTl
MYBPCl MYH6 ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl PRKACA
GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl ADCY7 RGS3
IGFBP6 RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2A RAMPl ATF5 ILlB PLCDl GNG4
MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5
GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA
GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT
CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADC Y6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl CAMK2B PRKCQ IGFBP3 RGS20
GABPA RGS6 CALCA SARAl GNAQ RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266 RGS17
CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2
GNG2 CAMK2D ADCY5 ITPR3 C6orfl25 ADCY4 MYLK2 LGR7 YWHAH GNBl PRKARlA IGFBP4 ETS2
Styrene degradation Styrene degradation FAH HGD TTN TNNT2 ACTA2
TPM3 TNNT3 ACTN4 MYL9 VIM DES TMODl ACTN2 ACTAl DMD TPM2
MYH7 NEB ACTC TNNIl TNNC2 MYL3 MYOMl TNNI3 TCAP MYH3 TPMl
TNNI2 MYBPC2 MYH8 ACTN3 MYBPC3 TPM4 MYL2 MYLl MYL4 TNNTl MYBPCl MYH6 ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl
PRKACA GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl
ADCY7 RGS3 IGFBP6 RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4
GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2 A RAMPl ATF5 ILlB
PLCDl GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR
GNG7 PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ
RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS
ADC Y6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl CAMK2B PRKCQ IGFBP3 RGS20 GABPA RGS6 CALCA SARAl GNAQ RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266
RGS 17 CORIN GNG 13 PRKCZ GUCYl A3 GNG3 ATFl GNB4 PKIB RGS 18
GBA2 GNG2 CAMK2D ADCY5 ITPR3 C6orfl 25 ADCY4 MYLK2 LGR7 YWHAH
GNBl PRKARlA IGFBP4 ETS2
Sulfur metabolism Sulfur metabolism SUOX BPNTl SULT2A1 SULTl A2 SULTl A3 SULTlEl GIYD2 DES TMODl ACTN2 ACTAl DMD TPM2 MYH7 NEB
ACTC TNNIl TNNC2 MYL3 MYOMl TNNT3 TNNI3 TCAP MYH3 TPMl TNNI2 MYBPC2 MYH8 ACTN3 MYBPC3 TTN TPM4 MYL2 MYLl MYL4
TPM3 TNNTl MYBPCl MYH6 TNNT2 ACTN4 ACTA2 ITPR2 ATF3 IGFBP2
PKIG PRKACB PLCGl PRKACA GRK6 ADM RGSl CREBLl ARRB2
PRKAR2B PDE4B ITPRl ADCY7 RGS3 IGFBP6 RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2A
RAMPl ATF5 ILlB PLCDl GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1
CAMK2B PRKCQ IGFBP3 RGS20 GABPA RGS6 CALCA SARAl GNAQ RLNl
GNG12 YWHAQ PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3
ADMR SPl ARRBl MGCl 1266 RGS17 CORIN GNG13 PRKCZ GUCYl A3
GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2 CAMK2D ADCY5 ITPR3 C6orfl25 ADCY4 MYLK2 LGR7 YWHAH GNBl PRKARlA IGFBP4 ETS2
Synthesis and degradation of ketone bodies Synthesis and degradation of ketone bodies ACATl
BDH HMGCL OXCTl BPNTl SULTlEl GIYD2 DES TMODl ACTN2 ACTAl
DMD TPM2 MYH7 NEB ACTC TNNIl TNNC2 MYL3 MYOMl TNNT3 TNNI3 TCAP MYH3 TPMl TNNI2 MYBPC2 MYH8 ACTN3 MYBPC3 TTN TPM4 MYL2 MYLl MYL4 TPM3 TNNTl MYBPCl MYH6 TNNT2 ACTN4
ACTA2 ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl PRKACA GRK6
ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl ADCY7 RGS3 IGFBP6
RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2A RAMPl ATF5 ILlB PLCDl GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3
PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCAlB SLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 CAMK2B PRKCQ IGFBP3 RGS20 GABPA RGS6 CALCA SARAl GNAQ RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl
ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266 RGS17 CORIN GNG13
PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2 CAMK2D
ADCY5 ITPR3 C6orfl25 ADCY4 MYLK2 LGR7 YWHAH GNBl PRKARlA IGFBP4
ETS2 Synthesis_and_Degradation_of_Keton_Bodies_KEGG Synthesis_and_Degradation_of_Keton_Bodies_KEGG ACATl BDH HMGCL OXCTl HMGCS2 GIYD2 SULTlEl BPNTl DES
TMODl ACTN2 ACTAl DMD TPM2 MYH7 NEB ACTC TNNIl TNNC2 MYL3 MYOMl TNNT3 TNNI3 TCAP MYH3 TPMl TNNI2 MYBPC2 MYH8 ACTN3
MYBPC3 TTN TPM4 MYL2 MYLl MYL4 TPM3 TNNTl MYBPCl MYH6 TNNT2 ACTN4 ACTA2 ITPR2 ATF3 IGFBP2 PKIG PRKACB PLCGl
PRKACA GRK6 ADM RGSl CREBLl ARRB2 PRKAR2B PDE4B ITPRl
ADCY7 RGS3 IGFBP6 RCP9 CNNl GNB5 EDG2 RGS14 RGSlO RGS19 RGS4 GRK5 PDE4D ADCY9 PKIA PLCG2 GABPB2 PRKAR2 A RAMPl ATF5 ILlB
PLCDl GNG4 MAFF IL6 IGFBPl RAMP3 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR
GNG7 PRKCA GUCA1BSLC8A1 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS
ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 CAMK2B PRKCQ
IGFBP3 RGS20 GABPA RGS6 CALCA SARAl GNAQ RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl ADCY2 ADCYl PLCB3 ADMR SPl ARRBl MGCl 1266
RGS17 CORIN GNG13 PRKCZ GUCYl A3 GNG3 ATFl GNB4 PKIB RGSl 8
GB A2 GNG2 CAMK2D ADCY5 ITPR3 C6orfl25 ADCY4 MYLK2 LGR7 YWHAH
GNBl PRKARlA IGFBP4 ETS2
TGF_Beta_Signaling_Pathway TGF Beta Signaling Pathway JAKl CTNNBl ITGB6 ZFHX1B TGFBR2 EP300 TFE3 SMAD4 LTBPl TGIF SPPl SERPINEl THBSl
JUN ENG CREBBP SM AD2 TGFBl MAPK9 RUNX3 FLJ 13941 TGFBR3 SMAD7
ZFYVE9 INHBA FST SMAD5 LIF EGF SMAD9 SKIL TGFBRl SMAD6 TNF FOXHl STAT3 FOS NFKBl LEFl SMADl BMP4 MAPK3 HRAS ZNF423 RUNX2 KIFC2 NOG RAVER2LOC441033 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR
GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2
ADCY6 SFN ADCY3 RGS16 CREB3 CACNB3CALM1 MYL2 CAMK2B PRKCQ
MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RRGGSS33 RRGGSS 1177 CORIN GNG 13 PPRRKKCCZZ GUCYl A3
GNG3 ATFl GNB4 PKIB RGSl 8 GGBBAA22 GGNNGG22 CAMK2D PPKKIIAA ADCY5
ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LLGGRR77 EEDDGG22 PRKACB YYWWHHAA]H GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 EETTSS22 IILL66 MAFF ILlB
Taurine and hypotaurine metabolism TTaauuririnnee a anndd hhyyppoetau jririnnee mmeettaabboolliissmm GAD2 GGAADDll BAAT
GGTl GGT2 THBSl JJUUNN CCTTNNNNBI l JJAAKKll EENNGG CREBBP EP300 SSMMAADD44 SERPINEl
LTBPl SMAD2 TGFBl MMAAPPKK99 TTGGIIFF ZFHXlB RUNX3 FLJ13941 TTGGFFBBRR3 SMAD7
ZFYVE9 INHBA FST SSMMAADD55 LLIIFF EGF SMAD9 TFE3 SKIL TTGGFFBBRRl SMAD6
TNF TGFBR2 FOXHl IITTGGBB66 STAT3 FOS NFKBl SPPl LEFl SSMMAADDll BMP4
MAPK3 HRAS ZNF423 RUNX2 KIFC2 NOG RAVER2LOC441033 AATTFF22 RYRl
NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7
RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl
CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PPRRKKCCBBl GRK4
CRHRl YWHAB RGS5 ATP2A2 ADCY6 SSFFNN ADCY3 RGS 16 CREB3 CCAACCNNEB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IIGGFFBBPP33 RGS20 GABPA RGS6 CCAALLCCAA SARAl PDE4D GRK6 RGS 14 PDE4B ITPRl IITTPPRR22 GNAQ CREBLl RLNl GGNNGG1l22 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 AADDCCYYll PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS 18 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orΩ25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB Terpenoid biosynthesis Terpenoid biosynthesis SQLE FDPS IDIl FDFTl THBSl
JUN CTNNBl JAKl ENG CREBBP EP300 SMAD4 SERPINEl LTBPl SMAD2 TGFBl MAPK9 TGIF ZFHXlB RUNX3 FLJ13941 TGFBR3 SMAD7 ZFYVE9 INHBA FST SMAD5 LIF EGF SMAD9 TFE3 SKIL TGFBRl SMAD6 TNF TGFBR2 FOXHl ITGB6 STAT3 FOS NFKBl SPPl LEFl SMADl BMP4 MAPK3 HRAS ZNF423 RUNX2 KIFC2 NOG RAVER2LOC441033 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCAl BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 ADCY6 SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNGl 3 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGSl 8 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Tetrachloroethene degradation Tetrachloroethene degradation EPHXl EPHX2 IDIl
FDFTl SQLE FDPS THBSl JUN CTNNBl JAKl ENG CREBBP EP300 SMAD4 SERPINEl LTBPl SMAD2 TGFBl MAPK9 TGIF ZFHXlB RUNX3 FLJ13941
TGFBR3 SMAD7 ZFYVE9 INHBA FST SMAD5 LIF EGF SMAD9 TFE3 SKIL TGFBRl SMAD6 TNF TGFBR2 FOXHl ITGB6 STAT3 FOS NFKBl SPPl LEFl SMADl BMP4 MAPK3 HRAS ZNF423 RUNX2 KIFC2 NOG RAVER2LOC441033 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 ADCY6 SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS 14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl
GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266
RGS3 RGS 17 CORIN GNGl 3 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS 18 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB Tetracycline biosynthesis Tetracycline biosynthesis ACACA IDIl SQLE FDFTl FDPS THBSl JUN CTNNBl JAKl EENNGG CREBBP EP300 SMAD4 SERPINEl LTBPl SMAD2 TGFBl MAPK9 TGIF ZZFFIHEXlB RUNX3 FLJl 3941 TGFBR3 SMAD7 ZFYVE9 INHBA FST SMAD5 LIF EEGGFF SMAD9 TFE3 SKIL TGFBRl SMAD6 TNF TGFBR2 FOXHl ITGB6 STAT3 FFOOSS NFKBl SPPl LEFl SMADl BMP4 MAPK3 HRAS ZNF423 RUNX2 KIFC2 NNOOGG RAVER2LOC441033 ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GGNNBB:3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PPRRKK(CA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 ADCY6 SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2
CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D
GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB
CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl
ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS 17 CORIN
GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS 18 GB A2 GNG2
CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2
PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6
MAFF ILlB
Translation_Factors Translation_Factors EIF4G3 EIF4A2 EIF2B5 EIF3S1 PABPCl
EIF3S7 EIF3S5 EEF2 EIF3S10 NANOSl EIF3S8 EEFlG EEF1B2 EIFlAX EIF5B EIF5A EIF2S1 EIF4E EIF4A1 ETFl EIF3S3 EIF2B1 SUIl EIF2B2 EEFlD EIF3S9 EIF2AK2 EIFlAY EEF1A2 EIF2S3 GSPT2 WBSCRl PAIPl EIF5 EIF4G1 EIF3S6 EIF2S2
EIF3S2 EIF4EBP2 ANKHDl EIF3S4 LOC388345 ITGB4BP KIAA0664
LOC143243 EIF2B4 EIF2AK1 EIF2B3 EIF2AK3EIF4EBP1 SLC35A4 EEF2K
REVlL TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl
NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4
CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6
CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl
GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2
ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266
RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB
RGS 18 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5
MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB Tryptophan metabolism Tryptophan metabolism CYP2E1 CYP2A6 TPHl CYP19A1
ACATl CYP4B1 SDS MAOB WARS2 DLX6 WARS ECHSl ALDH2 CAT ALDH3A2 CYP51A1 GCDH ABPl KYNU MAOA AOC3 CYP2J2 AOXl EHHADH
DDC HAAO CYPlAl CYP3A5 CYP3A7 TD02 CYP3A4 CYP2B6 ASMT ALDH 1A2 AOC2 AANAT CYP2D6 CYP 1A2 CYP2A7 CYP2F1 CYP2C18 CYP2C8 HADHA ALDHlBl INDO CYP2B7P1 CYP4F8 ALDHlAl CYP3A5P2 CYP2C9 CYP2C19
ACMSD EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2
FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3CALM1 MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA
PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3
GNG3 ATFl GNB4 PKIB RGS 18 GB A2 GNG2 CAMK2D PKIA ADCY5
ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Type II secretion system Type II secretion system DCTD CYP 19Al ACATl CYP4B1
SDS MAOB WARS2 DLX6 WARS ECHSl ALDH2 CAT ALDH3A2 CYP51A1 GCDH ABPl KYNU MAOA AOC3 CYP2J2 AOXl EHHADH DDC HAAO CYPlAl CYP3A5 CYP3A7 TDO2 CYP3A4 CYP2B6 ASMT ALDH 1A2 AOC2 AANAT CYP2A6 CYP2D6 CYP1A2 CYP2A7 CYP2F1 CYP2C18 CYP2C8 HADHA ALDHlBl CYP2E1 INDO CYP2B7P1 CYP4F8 ALDHlAl CYP3A5P2 CYP2C9 TPHl
CYP2C19 ACMSD EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3
LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH
RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl
GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB
RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl
PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3
ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3
RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18
GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2
LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Type HI secretion system Type III secretion system ATP6V1C2 ATP6V1B1 ATP6V0C
ATP6V0A1 ATP5O ATP6V0B ATP6V0E ATP6V1B2 ATP6V1F
ATP6V1A ATP6V1C1 ATP6AP1 ATP6V1E1 ATP6V1G1 ATP6V1D ATP6V0D1 ATP6V1G2 ATP5E ATP6V0A4 ATP6V1H ATP6V1G3
TD02 CYP3A4 CYP2B6 ASMT ALDH1A2 AOC2 AANAT CYP2A6 CYP2D6 CYP1A2
CYP2A7 CYP2F1 CYP2C18 CYP2C8 GCDH HADHA ALDHlBl CYP2E1 INDO
CYP4B1 CYP2B7P1 ALDH3A2 CYP4F8 KYNU CYP3A7 CAT ALDHlAl
MAOA CYP3A5P2 DDC CYP2C9 TPHl CYP2C19 CYP51A1 WARS2 ACMSD CYP19A1 CYP3A5 MAOB EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3
EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl
NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3
CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6
CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2
ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB
RGS 18 GB A2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5
MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA
IGFBP4 ETS2 IL6 MAFF ILlB
Tyrosine metabolism Tyrosine metabolism TAT TYR MAOB ALDH3B1 GOTl G0T2 FAH ALDH1A3 ABPl MAOA A0C3 ALDH3B2 AOXl
HGD DDC DCT ALDH3A1 HPD ADHlC DBH PNMT A0C2 ADH6
ADHlA TH COMT ADHlB TPO ADH7 ARVCF ADH4 ADHFEl LOC138948
ALDHlBl CYP2E1 INDO CYP4B1 CYP2B7P1 ALDH3A2 ASMT CYP4F8
KYNU CYP3A4 CYP2A6 CYP3A7 CAT ALDHlAl CYP3A5P2 CYP2A7 CYP2C9 TPHl CYP2D6 CYP2C19 CYP51A1 CYP2B6 WARS2 ACMSD CYP19A1
HADHA CYP3A5 EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2
FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCYl A3
GNG3 ATFl GNB4 PKIB RGS 18 GB A2 GNG2 CAMK2D PKIA ADCY5
ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Ubiquinone biosynthesis Ubiquinone biosynthesis NDUFA5NDUFA1 NDUFAI l ALDH3B1 GOTl G0T2 FAH ALDH1A3 ABPl MAOB MAOA AOC3 ALDH3B2
AOXl HGD DDC DCT ALDH3A1 HPD ADHlC DBH TYR PNMT
TAT A0C2 ADH6 ADHlA TH COMT ADHlB TPO ADH7 ARVCF ADH4 ADHFEl LOC138948 ALDHlBl CYP2E1 INDO CYP4B1 CYP2B7P1 ALDH3A2
ASMT CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT ALDHlAl CYP3A5P2 CYP2A7 CYP2C9 TPHl CYP2D6 CYP2C19 CYP51A1 CYP2B6 WARS2 ACMSD
CYP19A1 HADHA CYP3A5 EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY
TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3
CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl
YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA
SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266
RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB
RGSl 8 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5
MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA
IGFBP4 ETS2 IL6 MAFF ILlB Ubiquitin mediated proteolysis Ubiquitin mediated proteolysis TAX1BP3 UBE2I
UBE2S UBE2D3 UBE2E3 UBE2L3 UBE2D2 UBE2N UBE2L6 UBE2A UBE2B HIP2 UBE2C UBE2M UBE2G2 UBE2G1 UBE2D1 UBE2E1 CDC34 UBE2H UBE2J2 CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT ALDHlAl MAOA CYP3A5P2 CYP2A7 DDC CYP2C9
TPHl CYP2D6 CYP2C19 CYP51A1 CYP2B6 WARS2 ACMSD CYP19A1
HADHA CYP3A5 MAOB EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH
RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB
RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl
PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A ADCY2 ADCYl PLCB3
ADMR SPl ADC Y9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3
RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GB A2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2
LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4
ETS2 IL6 MAFF ILlB
Urea cycle and metabolism of amino groups Urea cycle and metabolism of amino groups GAMT
KIAA0377 ODCl CKB GLUDl OAT SMS PYCRl CKMTlB ACYl ARG2 ASL CKM CPSl CKMT2 ARGl ASS OTC GLUD2 ALDHl 8Al
NAGS CATSPER2 ABHD 14A UBE2E3 UBE2I UBE2B UBE2D1 UBE2E1 CDC34
UBE2N UBE2H UBE2D3 UBE2J2 HIP2 UBE2G1 UBE2G2 CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT ALDHlAl MAOA CYP3A5P2 CYP2A7 DDC CYP2C9 TPHl
CYP2D6 CYP2C19 CYP51A1 CYP2B6 WARS2 ACMSD CYP19A1 HADHA CYP3A5 MAOB EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033
LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 MYL2 CAMK2B
PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA
PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCYl A3 GNG3 ATFl GNB4 PKIB RGSl 8 GBA2 GNG2 CAMK2D PKIA ADCY5
ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Valine_leucine and isoleucine biosynthesis Valine_leucine and isoleucine biosynthesis PDHAl
LARS2 IARS PDHB BCATl PDHA2 MAP3K15 CPSl CKMT2 GAMT ARGl ASS OTC GLUD2 ALDHl 8Al NAGS GLUDl CATSPER2 ABHD 14A
UBE2E3 UBE2I UBE2B UBE2D1 UBE2E1 CDC34 UBE2N UBE2H UBE2D3 UBE2J2 HIP2 UBE2G1 UBE2G2 CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT ALDHlAl MAOA
CYP3A5P2 CYP2A7 DDC CYP2C9 TPHl CYP2D6 CYP2C19 CYP51A1
CYP2B6 WARS2 ACMSD CYP19A1 HADHA CYP3A5 MAOB EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB
TGIF ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20
GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl PRKAR2A
ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl
MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25
ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl
PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Valine_leucine and isoleucine degradation Valine_leucine and isoleucine degradation ACATl
SDS MCCC2 STAGl HADHB ECHSl ALDH2 ACAA2 ACAAl ALDH3A2 ACADS ACADM HMGCL OXCTl MUT IVD PCCA C14orf45 ALDH6A1 AOXl EHHADH
ALDH1A2 HADHA ALDHlBl BCKDHB ALDHlAl PCCB BCATl
MCCCl BCKDHA MYO5B UBE2I UBE2E1 UBE2H UBE2B UBE2J2 UBE2D3 HIP2
CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT MAOA CYP3A5P2 CYP2A7 DDC
CYP2C9 TPHl CYP2D6 CYP2C19 CYP51A1 CYP2B6 WARS2 ACMSD CYP19A1 CYP3A5 MAOB EIF3S6 EIF2AK3EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033
LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl NOS3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 PRKCA GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2
FOS ADCY6 NFKBl SFN ADCY3 RGS16 CREB3 CACNB3CALM1 MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14
PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G
CMKORl PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA
PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCY1A3
GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Vitamin B6 metabolism Vitamin B6 metabolism PDXK AOXl PNPO ALDH2 ACAA2
ACAAl ALDH3A2 ACADS ACADM HMGCL OXCTl MUT IVD PCCA C14orf45
ALDH6A1 EHHADH ACATl SDS ALDH 1A2 HADHA MCCC2 ALDHlBl BCKDHB ALDHlAl PCCB BCATl MCCCl BCKDHA MY05B UBE2I
UBE2E1 UBE2H UBE2B UBE2J2 UBE2D3 HIP2 CYP4F8 KYNU CYP3A4 CYP2A6 CYP3A7 CAT MAOA CYP3A5P2 CYP2A7 DDC CYP2C9 TPHl CYP2D6 CYP2C19
CYP51A1 CYP2B6 WARS2 ACMSD CYP19A1 CYP3A5 MAOB EIF3S6 EIF2AK3
EIF3S9 EIF4E EIF5 EIF4G3 EIFlAY TGFBR3 LOC441033 LTBPl CTNNBl STAT3 ZFHXlB TGIF ATF2 RYRl N0S3 CRH RAMP2 PRKDl USP5 GNB3 PRKCH
RGSI l GABPB2 PRKCE RGS7 RYR3 RGS9 ADC Y8 OXTR GNG7 PRKCA GUCAlB SLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A PRKCBl GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl
SFN ADC Y3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B PRKCQ MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B ITPRl
ITPR2 GNAQ CREBLl RLNl GNG12 YWHAQ PRKARlB CAMK2G CMKORl
PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl
RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 PRKCZ GUCYl A3
GNG3 ATFl GNB4 PKIB RGSl 8 GBA2 GNG2 CAMK2D PKIA ADCY5 ITPR3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl
ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB
Wnt_signaling Wnt_signaling PPP2R5C CTNNBl RHOA WNT4 PRKCBl PRKCH
PRKCA FBXW2 PPP2R5E CCND2 PRKCE RACl PRKCZ PAFAHlBl JUN
CCND3 DVL3 LDLR CSNKlE MYC PRKCD MAPK9 DVLl APC FZD7 FZD6 SFRP4 FOSLl FZDl MAPK10PLAU WNT2 PRKDl WNTl OBPRKCG WNT2B WNTI l
FZD9 CCNDl PRKCI GSK3B PRKCQ FZD2 WNT7A AXINl FZD8 WNT7B DVL2 FZD3 FZDlO FRATl WNT5B WNT16 C2orf31 WNT3 WNT6 WNT10ARGS7 RYR3 RGS9 ADCY8 OXTR GNG7 GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2
CAMK2B MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6
RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl RGSI l GNG12 YWHAQ PRKARlB CAMK2G CMKORl ATF2 PRKAR2A ADCY2 ADCYl PLCB3 ADMR
SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13 GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2
CAMK2D PKIA GABPB2 ADCY5 ITPR3 NOS3 C6orfl25 ADCY4 ATF5 MYLK2
LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4
ETS2 IL6 MAFF ILlB beta- Alanine metabolism beta- Alanine metabolism DPYD SDS GAD2 ECHSl ALDH2 SMS ALDH3A2 ACADM ABPl A0C3 EHHADH GADl DPYS ABAT
ALDH1A2 AOC2 HADHA ALDHlBl ALDHlAl CNDPl APC FZD7
FZD6 SFRP4 FOSLl FZDl MAPK10PLAU WNT2 PRKDl PRKCH WNTIOBPRKCE PRKCG WNT2B WNTI l PRKCA FZD9 PRKCBl WNT4 RACl CCNDl FBXW2 PRKCI GSK3B PRKCQ FZD2 WNT7A MAPK9 PAFAHlBl AXINl PPP2R5C FZD8 LDLR WNT7B DVL2 FZD3 FZDlO FRATl PRKCZ WNT5B WNT16 C2orf31 WNT3
WNT6 CSNKlE CTNNBl WNTl 0APPP2R5E MYC RGS7 RYR3 RGS9 ADCY8
OXTR GNG7 GUCA1BSLC8A1 GNB5 GNG5 GNGTl CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A GRK4 CRHRl YWHAB RGS5 ATP2A2 FOS
ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3 CALMl MYL2 CAMK2B MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl PDE4D GRK6 RGS14 PDE4B
ITPRl ITPR2 GNAQ CREBLl RLNl RGSI l GNG12 YWHAQ PRKARlB CAMK2G
CMKORl ATF2 PRKAR2A ADCY2 ADCYl PLCB3 ADMR SPl ADCY9
PRKACA PLCGl RGSl ARRBl MGCl 1266 RGS3 RGS17 CORIN GNG13
GUCY1A3 GNG3 ATFl GNB4 PKIB RGS18 GBA2 GNG2 CAMK2D PKIA GABPB2 ADCY5 ITPR3 N0S3 C6orfl25 ADCY4 ATF5 MYLK2 LGR7 EDG2
PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA IGFBP4 ETS2 IL6 MAFF ILlB gamma-Hexachlorocyclohexane degradation gamma-Hexachlorocyclohexane degradation CYP2E1
CYP2A6 CYP19A1 CYP4B1 ALPL ACP5 DLX6 CYP51A1 ACP2 ACPP
ALPP CYP2J2 CYPlAl CYP3A5 CYP3A7 CYP3A4 PONl CYP2B6 ALPI CYP2D6 CYP1A2 CYP2A7 CYP2F1 CYP2C18 CYP2C8 CYP2B7P1 ALPPL2 CYP4F8 CYP3A5P2
CYP2C9 CYP2C19 DDB2 ACPT GSK3B PRKCQ FZD2 WNT7A MAPK9 PAFAHlBl
PLAU AXINl PRKCA PPP2R5C PRKCI APC FZD8 PRKCE LDLR WNT7B
PRKDl DVL2 PRKCH FBXW2 FZD3 FZDlO FRATl PRKCZ WNT5B WNTl 6 C2orf31
WNT3 WNT6 CSNKlE CTNNBl WNT10APPP2R5E PRKCBl PRKCG MAPKlOMYC
RGS7 RYR3 RGS9 ADCY8 OXTR GNG7 GUCA1BSLC8A1 GNB5 GNG5 GNGTl
CALM2 NOSl GUCA2BATP2A3 DGKZ RYR2 OXT CAMK2A GRK4 CRHRl
YWHAB RGS5 ATP2A2 FOS ADCY6 NFKBl SFN ADCY3 RGS 16 CREB3 CACNB3
CALMl MYL2 CAMK2B MYL4 IGFBP3 RGS20 GABPA RGS6 CALCA SARAl
PDE4D GRK6 RGS14 PDE4B ITPRl ITPR2 GNAQ CREBLl RLNl RGSI l GNG12
YWHAQ PRKARlB CAMK2G CMKORl ATF2 PRKAR2A ADCY2
ADCYl PLCB3 ADMR SPl ADCY9 PRKACA PLCGl RGSl ARRBl MGCl 1266
RGS3 RGS 17 CORIN GNGl 3 GUCY1A3 GNG3 ATFl GNB4 PKIB RGS 18
GBA2 GNG2 CAMK2D PKIA GABPB2 ADCY5 ITPR3 NOS3 C6orfl25 ADCY4
ATF5 MYLK2 LGR7 EDG2 PRKACB YWHAH GNBl ACTA2 IGFBPl PRKARlA
IGFBP4 ETS2 IL6 MAFF ILlB mRNA_processing_Reactome mRNA_processing_Reactome CUGBP2 PTBP2 CUGBPl SMClLl FLJ45244 DDX20 SNRP70 SRPK2 SNRPN PARl SFRS8 C10orf31 SNRPB2 HRMTl L2 FUS SFRS 12 CLK4 PRPF8 HNRPC SFRS9 NONO RNPSl HNRPD
HNRPU SFRS2 SNRPD2 SFRSlO PPMlG TMED10HNRPH1 SF3B1 SFRS7 HNRPH2SRRM1 DDXl HNRPAB SF3A1 DHX15 RBM5 SUPT5H NCBP2 PABPNl CPSFl SFRS4
SNRPA HNRPL PRPF4B CLK3 PTBPl CSTFl SRPKl PRPF3 CD2BP2 DHX9 SNRPD3
RNMT SNRPDl NUDT21 POLR2A TXNL4AU2AF1 CLK2 SNRPE DHX8 CDC40 SFRS5
DHX 16 SF3A3 SNRPF CSTF3 RNGTT FUSIPl HEAB CSTF2 LSM7 SPOP SFRS16
HNRP A2B1 DNAJC8 SNRPG SNURF SNRPAl DICERl SFRS6 CPSF4 HNRP A3P1
HNRPA3 GIPCl RNPC2 LOC442610 YBXl HNRPR SNRPB C20orfl4NXFl SF3B4
PRPF4 DHX38 METTL3 SF3A2 DDIT3 PAPOLALSM2 NCBPl SF4 HIATLl SFRS 14
CSTF2T COL2A1 FNBP3 WDR57 U2AF2 SF3B5 RBM17 PRPFl 8 XRN2 BRUNOL4
CPSF3 LOC442518 PHF5A CPSF2 FRMD4A PRKGl UBE3A MGCl 5875
PRKACB CREB3 CALM2 GNAQ PRKCE YWHAH PDE4D GNBl ACTA2 PRKCQ
RGS 17 IGFBPl LGR7 SLC8A1 CAMK2G NOSl CORIN DGKZ NFKBl ATP2A2
ITPRl CAMK2D CALMl EDG2 RYR3 GRK4 RGS16 PRKARlA IGFBP4
ETS2 RYR2 GABPA GNG2 IL6 SFN CACNB3CAMK2B MAFF RGS 14
ILlB
NFkappaB Activators DCH NFkB activation genes taken from SuperArray CARDlO ILlB IL8 MYD88
TLRl TLR2 TLR3 TLR4 TLR6 TLR8 TNF TNFRSFlOA TNFRSFlOB
CARDI l CARD14 IRAKI IRAK2 HUK IKBKB IKBKG IRAKI IRAK2 MAP2K3MAP2K4
MKK4 JNKKl MAP2K6MAP3K14 NIK MAP3K7TAK1 MAPK14BCL3 ILlO
NALP 12 NFKBIA MAD3 TNFRSF7 TNFSF14 IKBKB IKBKG IRAKI NFKBl
NFKBIA RELA STATl TNF ILlB IL8 IRAK2 MYD88 NFKBl TLRl TLR2
TLR3 TLR4 TLR6 TLR8 TNF
NFkappaB Responsive DCH NFkB responsive genes from SuperArray AGT BF C3
ICAMl CSF2 CSF3 IFNAl IFNBl IFNG IL6 CCL2 CSF3 IFNAl IFNBl
IFNG IL6 IL8 LTA TNF
NFkappaB PositiveRegulators DCH NFkB and IKK postive regulators from SuperArray F2R GPR89
HTR2B LTBR SLC20A1 TICAM2 TNFRSFlA TNFRSF5 TNFSFlO
TNFSF6 TRIF EDG2 GJAl HMOXl RHOA VAPA IKBKE MAP3K3MAP3K7IP2
PLK2 RIPKl RIP RIPK2 TBKl APOL3 BCLlO BIRC2 CARD4 CASPl CASP8
CFLAR CTL2 CXXC5 ECMl FADD HNLF LITAF MALTl PPMlA PPP5C REL
RFP2 RHOC TRADD TRAF5 TRAF6 p53 Apoptosis DCH p53 associated apoptosis from SuperArray BAKl BAX BID CDKNlA
CRADD DAPKl EI24 FADD FOXO3APCBP4 PLAGLl PRKCA PYCARD TNFRSFlOB
TNFSF6 TP53 TP73 TP73L p53 Antiapoptosis DCH p53 associated antiapoptosis from SuperArray AATF BAGl BCL2 BCL2A1
BIRC5 BNIP3 CASP2 HDACl IGFlR MCLl NFKBl RELA SNCA TNF p53 Cell Cycle Arrest DCH p53 associated cell cycle arrest from SuperArray CDKNlA CDKN2A
CHEKl CHEK2 GADD45A GASl GML GTSEl MYC PCAF PCBP4 PLAGLl
PPP1R9B RPRM SESNl SESN2 SESN3 p53 OtherApoptosis DCH p53 other apoptosis genes from SuperArray APAFl BRCAl CASP9 DAXX
E2F1 FAFl GADD45A GML LRDD P53AIP1 PPP1R13B RAI SIAHl
SIRTl TP53BP2TRAF2 TRAF4 TRAF5 p53_Checkpoint_DCH p53 assoc checkpoint genes SuperArray ATR BRCAl CCNE2 CCNG2 CDKN2A RBl TP53 p53_Neg_Cell_Cycle_Reg p53 negative cell cycle regulators SuperArray ATM BAX BRCAl CDKN2A MSH2 NFl PTEN PYCARD RBl SMARCBl TP53 TP73 TP73L TSCl TSC2 WTl p53_Cell_Cycle_Reg_DCH p53 assoc cell cycle regulators SuperArray BRCA2 CDC2 CDC25A CDK4 CDK7 E2F1 E2F3 FRAPl GAK HK2 IGFlR KRAS2 PLKl PPMlD PRKCA SFN STATl TADA3LTP53BP2 p53_Neg_Reg_Proliferation_DCH p53 negative proliferation under differentiation SuperArray BAIl BAPl BCL2 BTG2 CDKNlA CDKN2A CHEKl GASl GML IFNBl IL6
MDM2 MDM4 NFl PCAF PMP22 PPMlD SESNl p53_Pos_Reg_Proliferation_DCH p53 positive proliferation under differentiation SuperArray CIAOl IGFlR
IL6 SHCl TSHR p53_Cell_Growth_Differentiation_DCH p53 cell growth and differentiation SuperArray COPEB CYR61
ESRl MCLl MYODl NDRGl PPP1R9B PRKCQ SCGB3A1 SHCl p53_Other_Growth_Prolif_Differ_DCH p53 other growth prolif differentiation SuperArray FOXO3A
JUN KRAS2 PHB PML PTTGl TSC2 p53_DNA_Repair_DCH p53 DNA repair SuperArray ATM ATR BRCAl BTG2 CCNH CDK7
FRAPl GADD45A MSH2 PTTGl TP53
Oxidative_and_metabolic_stress_DCH SuperArrayHS012.2 Stress and toxicity oxid and metabolic stress CAT CRYAB CYPlAl CYPlBl CYP2E1 CYP7A1 CYP7B1 EPHX2 FMOl FMO5 GPXl GSR GSTM3 HMOXl HMOX2 MT2A POR PRDXl PRDX2 PTGSl PTGS2 SODl SOD2 Heat_Shock_DCH SuperArray HSOl 2.2 Stress Toxicity Heat Shock DNAJAl DNAJB4 HSFl TCF5 HSPAlA HSPAlL HSPA2 HSP A4 HSP A5 GRP78 HSP A6 HSPA8 HSP A9B HSPBl HSP27 HSPCA HSP90AA1 HSP90AB1 HSPCB HSP90B1 HSPDl HSPEl HSPHl HSP 105
Growth_Arrest_Senescence_DCH SuperArray HSO 12.2 Stress Toxicity Growth Arrest Senescence CDKNlA DDIT3 GADD153 CHOP GADD45A GADD45B GDF15 PLAB IGFBP6
MDM2 TP53 Inflammation DCH SuperArray HSO 12.2 Stress Toxicity Inflammation CCL3 CCL4 CCL21
CXCLlO CSF2 ILIA ILlB IL6 ILl 8 LTA MIF NFKBl NOS2A SERPINEl DNA_Damage_and_Repair_DCH SuperArray HSO 12.2 Stress Toxicity DNA damage and repair ATM
CHEK2 RAD53 DDBl ERCCl ERCC3 ERCC4 ERCC5 RAD23A RAD50 UGTlAlO UNG XRCCl XRCC2 XRCC4 XRCC5
Hemopoietic_Lineage_Markers_DCH SuperArray EHS405 Stem Cell Hemo Lineage Markers CD 19
CD3D CD3E CD3G CD3Z CD4 CD8A CD8B1 MME MS4A1 PTPRC TFRC
Stem_Cell_Cell_Cycle_Regulators_DCH SuperArray EHS405 Stem Cell Cell Cycle Reg APC AXINl
CCNA2 CCNDl CCND2 CCNEl CDC2 CDC42 CDK2 CDK4 CDK6 CDKNlA CDKN2A CDKN2B EP300 FGFl FGFlO FGF2 FGF3 FGF4 FGF5 FGF6 FGF7 FGF8 FGF9 HDAC9 JAG2 MYC NOTCH2PARD6APARD6B PARD6G PDGFA PDGFB PR48 PTEN RBl RHOB TP53
Stern_Cell_Chromatin_Modulators_DCH SuperArray EHS405 Chromat Modulators GCN5L2 HDAC 1
HDAC2 HDAC9 MYSTl MYST2 MYST3 MYST4 PCGF4 PSENl PSEN2 RBl SOX3
TERT
Stem_Cell_Symmetric_Asymmetric_Division_DCH SuperArray EHS405 Symmetric and Asymmetric Division
Genes DHH IHH NOTCHl NOTCH2NOTCH3NOTCH4NUMB PARD6APARD6B PARD6GPIWIL2
PRKCI PROXl PSENl PSEN2 SHH SNAIl SNAI2 SNAI3 STAU STAU2 Stem_Cell_Self_Renewal_Markers_DCH SuperArray EHS405 Stem Cell Self renewal HSP A9B MYSTl
MYST2 MYST3 MYST4 NEUR0G2 SOXl SOX2 SOX3
Stem_Cell_Cytokines_Growth_Factors_DCH SuperArray EHS405 Stem Cell Cytokines BMPl BMPlO
BMP 15 BMP2 BMP3 BMP4 BMP5 BMP6 BMP7 BMP8A BMP8B CXCLl 2 FGFl
FGFlO FGFI l FGF 12 FGF 13 FGF 14 FGF 16 FGFl 7 FGFl 8 FGF19 FGF2 FGF20
FGF21 FGF22 FGF23 FGF3 FGF4 FGF5 FGF6 FGF7 FGF8 FGF9 GDFlO
GDFI l GDF2 GDF3 IGFl JAGl JAG2 KITLG LIF PDGFA PDGFB SPPl
TDGFl
Stem Cell CellCell Communication DCH SuperArray EHS405 Stem Cell Cell Cell Communic DHH
DLLl GJAl GJAlO GJA3 GJA4 GJA5 GJA7 GJA8 GJBl GJB2 GJB3
GJB4 GJB5 GJB6 GGJJBB77 GJCl GJEl IHH JAGl JAG2 SHH
Stem Cell Cell Adhesion ] DCH SSuuppeerr/Array EHS405 Stem Cell Adhesion AGCl APC BGLAP
CD4 CD44 CDHl CCDDHHKlO CDHI l CDH12 CDH13 CDH15 CDH2 CDH3 CDH4
CDH5 CDH6 CDH7 CCDDHH88 CDH9 COL9 Al CTNNAl CTNNBl CXCL 12 ITGA2 KITLG
NCAMl RACl RHOB SSPPPP
Stem Cell Metabolic Markers DCH SSuuppeerr/Array EHS405 Metabolic markers ABCG2 ALDHlAl
ALDH2 FGFRl FGFR2 FFGGFFRR23 FGFR4 FIBP PDGFRA Stem_Cell_Embroyonic_Lineage_Markers_DCH SuperArray EHS405 Embryonic Lineage ACTC ASCL2
FOXA2 IPFl ISLl KRT15 MSXl MYODl
Stem_Cell_Mesenchymal_Lineage_Markers_DCH SuperArray EHS405 Mesenchymal AGCl ALPI
ALPL ALPP ALPPL2 BGLAP COLlOAl COLlAl COL2A1 COL9A1 PPARG SPPl Stem_Cell_Neural_Lineage_Markers_DCH SuperArray EHS405 Neural Markers CD44 NCAMl OPRSl
SlOOB TUBB3 Stem_Cell_Misc_Lineage_Markers_DCH SuperArray EHS405 Misc Markers FLT3 KIT KITLG
MEF2A MYF5 MYF6 Stem_Cell_Maintenance_Notch_DCH SuperArray EHS405 Stem Maintenance Notch Pathway ADAM17
APH-IA CIR CREBBP CTBPl CTBP2 DLLl DLL3 DTXl DTX2 DVLl EP300
GCN5L2 HDACl HDAC2 HESl HES5 JAGl JAG2 LFNG MAMLl MAML2 MFNG NCOR2 NCSTN NOTCHl NOTCH2NOTCH3NOTCH4NUMB NUMBL PEN2 PSENl PSEN2 PSFL PTCRA RBPSUHRBPSUHL SKIIP
Stem_Cell_Maintenance_Wnt_DCH SuperArray EHS405 Stem Maintenance Wnt Pathway ADAR APC
AXINl BTRC CCNDl CSNK1ACSNK2A1 CTBPl CTNNBl EIF4E FRATl FZDl
GSK3B HDAC9 HNF4A MAP3K7MAP3K7IP1 MYC NLK PPARD PR48 SMAD4
TLEl WIFl WNTl Cancer_Androgen_Pathway_DCH SuperArray HS-044 CDK2 CDKNlA EGFR FOLHl
KLK2 KLK3 TMEPAI Cancer_Cox2_Pathway_DCH SuperArray HS-044 FOS HSPA4 MCLl PPARG PTGS2
TNFRSFlOB Cancer_DNA_Damage_and_p53_DCH SuperArray HS044 BAX BCL2 CDKNlA GADD45A
HIFlA HSP A4 IGFBP3 MDM2 PIG3 TNFRSF6 TNFRSFlOB TRAFl WIGl Cancer_Estrogen_Pathway_DCH SuperArray HS044 BCL2 BRCAl CTSD EGFR PGR ZNF147 Cancer_Hedgehog_Pathway_DCH SuperArray HS044 BMP2 BMP4 ENl HHIP F0XA2 HNF3B
PTCH PTCH2 WNTl WNT2 WSBl Cancer_Hypoxia_Pathway_DCH SuperArray HS044 ADRA IBCDKN IA EDNl EPO HKl
HMOXl IGFBP3 NOS2A SLC2A1 TF TFRC VEGF Cancer_Inflamrnation_NFkB_DCH SuperArray HS044 ICAMl IL2 LTA NFKBl NFKBIA NOS2A
PECAMlTNF VCAMl Cancer_MAPK_Pathway_DCH SuperArray HS044 COLlAl EGRl FOS JUN Cancer_PI3K_Pathway_DCH SuperArray HS044 BCL2 CCNDl FNl HIFlA JUN MMP7
MYC TNFSFlO Cancer_STAT_Pathway_DCH SuperArray HS044 A2M BCL2 BCL2L1 CSN2 CXCL9 MIG
IL4 IL4R IRFl MMPlO NOS2A Cancer_Stress_p38_JNK_DCH SuperArray HS044 ABCBl MDRl ATF2 COLlAl DUSPl MKPl
ENPP2 FOS HSPA4 HSP A5 HSPBl HSPB2 MYC TP53 Cancer Survival NFkB DCH SuperArray HS044 AKTl BCL2A1 BCL2L1 BIRCl NAIP BIRC2
BIRC3 TNFAIP3 TRAFl Cancer TGFbeta DCH SuperArray HS044 CDKNlA CDKNlB CDKNlC CDKN2A
CDKN2B CDKN2C CDKN2D
Cancer_Wnt_DCH SuperArray HS044 ABCBl MDRl BMP4 CCNDl ENPP2 FOSLl ID2 JUN
MMP7 MYC VEGF WISPl HSC Hemo Lineage DCH SuperArray OHS054 CCRl CD 164 CDlD CD2 CD34 CD3D
CD3G CD4 CD44 CD80 CD86 CD8A CSFl DLLl FLT3LG FUTlO FZDl
GALNAC4S-6ST IL31RA IL6ST JAGl JAG2 KDR KIT KITLG LRMP MAL
NOTCH2NOTCH4PECAM 1 PTPRC SFXNl STIM2 TEK TLR3 TLR4 TNFRSF7
TNFSFI l HSC_Hemo_Cytokines_Growth_Factors_DCH SuperArray OHS054 CSFl CSF2 FLT3LG ILlO
ILI l IL12B IL17E ILIA IL2 IL20 IL4 IL7 INHA INHBA PF4
SPPl THPO TNFSFI l CSFl CSF2 ILlO ILI l ILIA IL2 IL4
IL7 INHA INHBA JAGl JAG2 KITLG SPPl THPO VEGF
HSC_Hemo_Cell_Cycle_Regulators_DCH SuperArray OHS054 CDKNlB 3 INHA INHBA
MYC NOTCH2APC GFIl HDAC4 HDAC5 HDAC7A HDAC9 ILIA JAG2
SCANDl STATl VEGF HSC_Herno_B_Cell_Activation_DCH SuperArray OHS054 HDAC4 HDAC5 HDAC7A HDAC9
IL4. HSC_Herno_T_Cell_Activation_DCH SuperArray OHS054 CD2 CD3D CD3G CD80 CD86
CD8A IRF4 HSC_Hemo_Other_Cell_Activation_DCH SuperArray OHS054 CD2 ILI l ILl 2B IL2
IL31RA PF4 TLR4 HSC_Hemo_B_Cell_Differentiation_DCH SuperArray OHS054 AICDA BLNK GALNAC4S-6ST
HDAC4 HDAC5 HDAC7A HDAC9 ILlO ILI l IL4 INHA INHBA KLF6
TNFRSF7 HSC_Hemo_T_Cell_Differantiation_DCH SuperArray OHS054 CD2 CD4 CD80 CD86
IL12B IL2 IL27 IRF4 JAG2 NOS2A RHOH SOCS5 TNFRSF7 WWPl HSC_Hemo_Other_Cell_Differentiation_DCH SuperArray OHS054 ANGPTl BGLAP CD3G CSFl
DLLl IFI16 ILI l IL20 IL31RA INHA INHBA JAGl MAL MAP4K1 MLF1
NCOA6 NOTCHl NOTCH2NOTCH4P PAAXX55 PF4 RASGRP4 SCANDl I SPPl TALI
TLR3 TLR4 TNFSFl 1 HSC_Hemo_Hematopoiesis_Regulators_DCH Super Array OHS054 ASH2L BCLI lA CDl 64 CSFl DLLl ERAF FEZ2 FUTlO IFI 16 ILlO IL20 IL31RA JAGl LMO2 MLFl MMP9 NOTCH2NOTCH4STIM2 TRIMlO ZNF160
HSC_Hemo_Signaling_Molecules_Notch Super Array OHS054 DLLl JAGl JAG2 NOTCH NOTCH4
HSC_Hemo_Signaling_Molecules_Wnt SuperArray OHS054 APC FZDl LEFl WNT3A
HSC_Hemo_Signaling_Molecules_JAKSTAT SuperArray OHS054 IL31RA SOCS5 STATl STAT3 STAT4
HSC_Hemo_Signaling_Molecules_CellSurface_Receptor_Linked_Signal_Trans SuperArray OHS054
CCRl CD14 CD2 CD3D CD3G CD4 CSF2 FZDl IL6ST INHA INHBA PRL PTPRC TNFRSF7
HSC Hemo Signaling Molecules Txpn Factors and Regulators SuperArray OHS054 ASH2L BCLI lA
CBFB CD80 CD86 CEBPE CEBPG EGRl ETSl ETV6 GATAl GATA2 GFIl HDAC4 HDAC5 HDAC7A HDAC9 HOXB4 IFI16 IL31RA IRF4 IRF8 KLF6
LEFl MAFB MYC NCOA6 NFYA NOTCH 1NOTCH2NOTCH4PAX5 RBPSUHRHOH RUNXl SCANDl STATl STAT3 STAT4 TALI VAVl WWPl ZNF160
Drug_Metabolism_PhaseI_Metabolism_DCH SuperArray APH002A P450 gene family CYPl 1B2
CYP17A1 CYP19A1 CYPlAl CYP2B6 CYP2C19 CYP2C8 CYP2C9 CYP2D6
CYP2E1 CYP2F1 CYP2J2 CYP3A5
Drug_Metabolism_PhaseII_Metabolism_DCH SuperArray APH002A transferases and hydrolases CES2 CES4 GADl ADHlB ADHlC ADH4 ADH5 ADH6 ALAD ALDHlAl HSD17B1 HSD17B2 HSD17B3 GPXl GPX2 GPX3 GPX4 GPX5 GSTA3 GSTA4
GSTM2 GSTM3 GSTM5 GSTPl GSTTl GSTZl LPO MPO EPHXl FAAH FBPl HK2 PKLR PKM2 ALOX12 ALOX15 ALOX5 APOE BLVRA BLVRB DIAl GPXl GPX2 GSR MTHFR NOS3 NQOl SRD5A1 SRD5A2 PONl PON2 PON3 CHSTl
GSTA3 GSTA4 GSTM2 GSTM3 GSTM5 GSTPl GSTTl MGSTl MGST2 MGST3 NATl
NAT2 COMT GGTl Drug_Metabolism_Transporters_DCH SuperArray APH002 DCH Manually Expanded Isoforms for ABCCl and ABCB
MT2A MT3 ABCB9 ABCB4 ABCB4 ABCB5 ABCB4 ABCBl ABCB9 ABCBI l ABCB9
ABCBl ABCB5 ABCB7 ABCB8 ABCB7 ABCB4 ABCB5 ABCB6 ABCBl ABCBlO ABCB5
ABCB6 ABCBI l
MDRl ABCC13 ABCCI l ABCC13 ABCC12 ABCClO ABCC13 ABCC13 ABCC12 ABCCl ABCCI l
ABCCl ABCClO GPI Drug_Metabolism_Other_DCH SuperArray APH002 ABPl AHR ARNT ASNAl GCKR
MARCKS SMARCALl SNN
Apoptosis_TNFligand_DCH SuperArray EHS012 LTA TNF TNFSF5 TNFSF6 TNFSF7 TNFSF8
TNFSF9 TNFSFlO TNFSF 14 TNFSF 18
Apoptosis_TNFreceptor_DCH SuperArray EHSO 12 LTBR TNFRSFlA TNFRSFlB
TNFRSF5 TNFRSF6 TNFRSF6B TNFRSF7 TNFRSF9
TNFRSFlOA TNFRSFlOB TNFRSFlOC TNFRSFlOD TNFRSFI lB
TNFRSF12A TNFRSF14 HVEM TNFRSF19 TNFRSF21 TNFRSF25
Apoptosis_BCL2_Family_DCH SuperArray EHSO 12 BAD BAGl BAG3 BAG4 BAKl
BAX BCL2 BCL2A1 BCL2L1 BCL2L2 BCL2L10 BCL2L11 BCL2L12
BCL2L13 BCLAFl BID BIK BNIPl BNIP2 BNIP3 NIP3 BNIP3L BOK
HRK MCLl Apoptosis_Caspase_DCH SuperArray EHSO 12 CASPl CASP2 CASP3 CASP4 CASP5 CASP6
CASP7 CASP8 CASP9 CASPlO CASP14 Apoptosis IAPJDCH SuperArray EHSO 12 BIRCl BIRC2 BIRC3 BIRC4 BIRC5 BIRC6
BIRC7 BIRC8
Apoptosis_TRAF_DCH SuperArray EHSO 12 TRAF 1 TRAF2 TRAF3 TRAF4 TRAF5 CRAFl Apoptosis CARD DCH SuperArray EHSO 12 AP AF 1 BCLlO BIRC2 BIRC3 CARD4 NODl
CARD6 CARD8 CARD9 CARD 10 CARD 11 CARD 12 CARD 14 CARD 15 CASPl CASP2 CASP4
CASP5 CASP9 CRADD NOL3 PYCARD RIPK2 Apoptosis_Death_Domain_DCH SuperArray EHSO 12 CRADD DAPKl DAPK2 FADD RIPKl
TNFRSFlOA TNFRSFlOB TNFRSFI lB TNFRSFlA TNFRSF21 TNFRSF25
TNFRSF6 TRADD
Apoptosis_CIDE_DCH SuperArray EHSO 12 CIDEA CIDEB DFFA DFFB Apoptosis_p53 DCH SuperArray EHSOl 2 ABLl AKTl APAFl BAD BAX BCL2
BCL2L1 BID CASP3 CASP6 CASP7 CASP9 GADD45A TP53 TP53BP2TP73
TP73L Apoptosis_anti_apoptosis_DCH SuperArray EHSO 12 AKTl BAGl BAG3 BAG4 BCL2
BCL2A1 BCL2L1 BCL2L10 BCL2L2 BFAR BIRCl BIRC2 BIRC3 BIRC4 BIRC5
BIRC6 BIRC7 BIRC8 BNIPl BNIP2 BNIP3 BRAF CASP2 CFLAR GDNF IGFlR
MCLl TNF TNFRSF6 TNFRSF6B TNFRSF7 TNFSFl 8 TNFSF5
Interferons_IFN_Induced_Virus_DCH SuperArray APH064 G1P2 IFI16 IFI35 IFI44 IFIHl
MXl OASl Interferons_IFN_Inducible_DCH SuperArray APH064 ADAR CXCLlO G1P3 IFI27 IFI30
IFI44L IFITl IFITlL IFIT2 IFIT3 IFITMl IFITM2 IRGM PSMEl PYHINl
Interferons_IFN_Txpn_Regulators_DCH SuperArray APH064 IFI 16 SPI lO
Interferons_IRFs_DCH SuperArray APH064 IRFl IRF2 IRF3 IRF4 IRF5 IRF6 IRF7 IRF8 IRF2BP1 IRF2BP2
Interferons_Receptors_Hematopoietin_and_D200_Class_DCH SuperArray APH064 CNTFR CRLF2
CSF2RA CSF3R EBI3 F3 FNDC6 ILlORA ILlORB ILHRA IL12B IL13RA1 IL20RA
IL21R IL22RA2 IL28RA IL2RB IL2RG IL31RA IL3RA IL4R IL5RA IL6R IL7R IL9R LEPR MPL TTN Interferons_Receptors_AlphaBetaGamma_DCH SuperArray APH064 IFNGRl IFNGR2 IFNARl IFNAR2
Interferons_Ligands_AlphaBetaGamma_DCH SuperArray APH064 IFNAl IFNA4 IFNBl IFNK
IFNWl IFNG
Interferons_Ligand_Hematopoietin_and_D200_Class_DCH SuperArray APH064 IFNA14 IFNA2
IFNA21 IFNA5 IFNA6 IFNA8 IFNEl IL15 Interferon_AB_Response_Element_DCH SuperArray HS054 genes with IRF response element ADAR
CASPl Clorf29 CXCLlO INPlO G1P3 GBPl GBP2 IFI16 IFITl IFIT2 IFIT5
IFITMl IRFl ISGF3G KIAA1268 LAMPl MXl MYD88 NMI OASl OAS2
PRKRA PSME2 STATl TAPl TNFSFlO TRIM34
Interferon_AB_Intrinsic_IFN_Resistance_DCH SuperArray HS054 genes assoc w intrinsic IFN resistance ARL5 CAVl IL2RB MAL MAP2K1 OASL PLA2G1B PRKCZ PRKRA PKR PRKRIPl
SAMSN1 SH2D1A BAG3 DADl DIABLO PML DNAJB2 HSPA6 ATF5 CBFB IRF2
IRF3 IRF5 MYC PTTGl CDKNlB H19 HOXB2 IFI16 IFITMl MET
MNT RCBTBl RCCl TNFSF7 VEGF B2M BST2 CNP COL16A1 FLJ42280
DSSl GIP2 IFI-15K HLA-A HLA-B IFI30 IFIT4 IFITM2 IFNG IFNWl IFRDl IFRD2 KLK3 LAMPl MX2 OASl OAS2 OASL SLC 1A2
Interferon_AB_HCV_Induced_IFN_Resistance_DCH SuperArray HS054 CASPl Clorf29 C6orf85 FLJ22174
GBPl GCHl G1P3 IFI16 IFI27 IFI35 IFI44 IFITl ISG20 ISGF3G ITIH2 KIAA1268 NRGl HGL STATl TRIM22 STAF50
4. Molecule Set Analysis Technique
47. The disclosed methods utilize various molecule set analysis techniques. Such techniques include, but are not limited to GSEA, PAGE, RAGE-RankProd, and RAGE- resampling. Thus, for example, disclosed herein are method for identifying treatments comprising one or more perturbations having anti-cancer activity wherein the molecule set analysis technique is computed by one or more of the techniques consisting oft-test, z-test, Mann- Whitney U test, Kolmogrov-Smirnov two sample test, Wilcoxon rank sum test, Wilcoxon signed-rank test, ANOVA, Kruskal-Wallis analysis of ranks, WaId- Wolfowitz runs test, Friedman test, sign test, Rank Product analysis RAGE-RankProd, RAGE- resampling algorithm, Rankind, Rankrel, contab, oneway, regress, pair, and Significance Analysis of Microarrays (SAM). For example, to perform the disclosed methods of identifying a perturbation, one of skill in the art first determines all gene expression differences between a first and second cell (e.g., untreated and treated cells) on, for example, a Iog2 scale, on a microarray (which results in Iog2 fold-changes for each gene). Second, fold changes are identified for genes belonging to gene set "A", which are, in this hypothetical example, genel = 0, gene2 = -1, gene3 = -2, gene4 = -0.5. Third, the genes in gene set "A" are used as one group for a two-sample test vs. a second group comprising gene expression differences for all other genes. It is understood that the methods disclosed herein are not limited to analyses between only two cells. Disclosed herein are methods of identifying a treatment comprising perturbations having anti-cancer activity, comprising obtaining a third, fourth, fifth, and/or sixth cell. It is understood that a particular molecule set analysis technique may be more appropriate than others depending on the number of cells used.
5. Gene Set Enrichment Analysis (GSEA)
48. Gene set Enrichment Analysis (GSEA) is a computational method developed by Subramanian et al. (Subramanian et al. (2005) PNAS 102: 15545-15550) that first ranks genes in a gene expression experiment according to correlation to a particular class (e.g. treatment) as determined by a user-selected measure, such as fold change or signal to noise. Then, for a predetermined set of genes (or "gene set" i.e., genes sharing a common feature such as chromosomal location, regulation, or biological function), it determines whether genes within the gene set are distributed randomly on the ordered list or enriched at the top or bottom of the list. This enrichment is computed by an enrichment score derived from a modified Kolmogorov-Smirnov statistic. A statistically significant enrichment is interpreted as evidence suggesting that the predefined biological relationship exemplified by the gene set is biologically relevant. Though powerful, a significant score is derived if genes in the gene set are grouped together on the ordered list. 6. Robust Analysis of Gene Expression (RAGE)
49. Robust Analysis of Gene Expression (RAGE) is a unique variation on GSEA. Unlike GSEA, RAGE looks for unusually high groupwise perturbations in gene expression for genes belonging to a gene set. The level of perturbation is determined using a median or other robust average of the expression differences observed between a test condition and its control (or of absolute expression values), hereinafter referred to as "perturbation score". The significance of the perturbation score is determined in one of two ways depending on experimental circumstances. When biological replicates are available, a matrix of n gene sets x p samples are submitted to rank product analysis (Breitling et al. FEBS Lett. 2004 Aug 27;573(l-3):83-92), where the matrix is populated with perturbation scores. Briefly, in this case, rank product analysis examines the probability of a perturbation score ranking high on a number of lists (replicates in ascending and then descending order) of perturbation scores to produce an RP- value. The significance of the RP- value is computed by generating random experiments and ascertaining the frequency at which an RP-value occurs by random chance. An advantage of this technique is consideration of the expression magnitude as well as insensitivity to outliers. When biological replicates are not available or it is otherwise considered desirable to compare a single test vs. control pair, a perturbation score is computed as above for one or more gene sets. The statistical significance of each gene set within the test vs. control pair is then estimated by randomly sampling expression differences for B random gene sets consisting of the same number of genes as the gene set of interest to determine how unusual a perturbation score is for a given gene set size, hi order to limit the number of samplings, one skilled in the art can choose to utilize the mean and standard deviation of B randomly sampled values to compute a normal or other probability denisty function from which statistical significance may be ascertained, hi addition, to avoid sampling expression differences repeatedly for gene sets consisting of the same number of genes (N), the sampling results for a gene set of size N can be stored to a memory and later retrieved when encountering a gene set of the same size N. hi this mode, it is possible to obtain a significance-ordered list of gene sets for a particular treatment tested in a microarray experiment.
50. As referred to herein, "statistical substitute" is a statistic that summarizes a set of observations such as the log ratios (Iog2(treatment/control)) arising from member genes of a gene set. Typically a useful statistic is any measure of location, such as the mean, median, or trimmed mean. The arithmetic mean, however, may be overly influenced by outliers in a gene set. hi the relevant RAGE procedure, expression differences for genes in a gene set are summarized by 1-step Tukey biweight mentioned in article "Robust estimators for expression analysis" Hubbell et al. Bioinformatics 18(12):1585(2002) which is included herein by reference in its entirety. This statistic reportedly works well in the presence and absence of outliers. The code in the computer languge, R, used to generate this statistic in RAGE is:
tukey .biweight <- function (x, c = 5, epsilon = le-04)
m <- median(x) s <- median(abs(x - m)) u <- (x - m)/(c * s + epsilon) w <- rep(0, length(x)) i <- abs(u) <= 1 w[i] <- ((I - uΛ2)Λ2)[i] t.bi <- sum(w * x)/sum(w) return(t.bi) where x is a vector (set) of log2 expression ratios of case / control for genes in a particular gene set (e.g. for 5 genes, there are 5 log ratios). The 1-step Tukey biweight is one example of statistics for computing a robust average and belongs to a larger class of estimators of location termed M-estimators (Huber 1981). Another example would be utilizing a median for the fold changes in a gene set. For geneset "A" with values (0, -1, -2, -0.5), for example, the MEDIAN would be -0.75. The gene sets of the same size (4 genes in this case) are repeatedly resampled from all of the fold changes for all genes in the microarray. Then, a determination is made of how unusual it is to obtain a median fold change of magnitude - 0.75. It is understood that any statistical substitute as defined herein can be used in the disclosed methods. Thus, for example, disclosed herein are methods wherein the statistical substitute is a robust average such as the statistic generated in RAGE.
7. Connectivity Map 51. The Connectivity Map is a gene expression repository comprising a compendium of microarray gene expression data obtained from cells in a particular biological state. Generally, such states can arise from exposure to small molecules/drugs, RNAi, gene transduction, gene knockout, mutation, or disease. Connectivity Map is able to independently obtain a gene expression signature arising from a treatment of interest (query signature) and identify instances of biological states within the Connectivity Map most similar to this query signature. Thus, any known or unknown biological state can be connected to a known biological state based on microarray gene expression data. Therefore, disclosed herein are methods of identifying compositions having anti-cancer activity, wherein the process of identifying of molecules which modulate the related molecule set is performed by using data from the Connectivity Map.
8. Methods of identifying a treatment for a disease
52. Disclosed herein are methods of identifying a treatment for a disease comprising a) comparing the molecular abundance between samples either treated or untreated with an agent known to reduce the disease condition; b) identifying molecules with significant molecular abundance; c) identifying molecules found in significant molecule sets using a molecule set analysis technique; d) identifying perturbations that modulate molecules within molecule sets using a gene expression repository; wherein perturbations that affect said molecules are treatments for the disease. It is contemplated herein that significant molecules can be identified using any number of criteria including simple fold change or by molecule set analysis techniques as disclosed herein, including, but not limited to, t-tests, z- tests, Mann- Whitney U test, Kohnogrov-Smirnov two sample test, Wilcoxon tests (Wilcoxon rank sum test and Wilcoxon signed-rank test), ANOVA, Kruskal-Wallis analysis of ranks, WaId- Wolfowitz runs test, Friedman tests, sign test, RAGE (including but not limited to RAGE-RankProd, and RAGE-resampling algorithm), PAGE, GSEA, Rank Product analysis (RankProd), Rankind, Rankrel, contab, oneway, regress, pair, Significance Analysis of Microarrays (SAM), etc.. The cutoff for differential expression can be amount of fold change, p- value, test statistic, or combination thereof. It is routine practice to adjust the raw p-values arising from statistical tests for multiple testing using a multiple test correction technique (e.g. Bonferroni). A statistical cutoff or fold change cutoff is not strictly required. The disclosed methods utilize various molecule set analysis techniques. Such techniques include, but are not limited to GSEA, PAGE, and RAGE.
53. It is understood that the disclosed method can further comprise identifying one or more additional perturbations that affect the same pathway, wherein the perturbations identified in step d individually only affect of subset of pathway of genes involved in the pathway, but in combination show pathway complementation. It is understood that when one or more perturbations are identified that affect the same pathway, the use of both perturbations can have a synergistic effect on the pathway. 54. It is contemplated herein that one result of the disclosed methods is the identification of perturbations that alone do not treat a cancer, but can increase the sensitivity of a disease to a treatment regimen. Thus, disclosed herein are methods of increasing the sensitivity of a disease to a treatment regimen comprising administering to the subject a treatment comprising one or more perturbations identified by the methods disclosed herein. It is understood and herein contemplated that a perturbation that negatively regulates protective genes can accomplish this task by inhibiting known pathways. For example, disclosed herein are methods, wherein the perturbation the negatively regulates protective genes is a form of PB kinase pathway inhibitor. Also disclosed are methods wherein the PB kinase pathway inhibitor is selected from the group consisting of rapamycin, LY-294002, or wortmannin.
55. The methods disclosed herein utilize diseased samples. Such samples can comprise primary cells from a subject with a disease or condition. For example, the subject can have AML or CML. Thus, it is contemplated herein that the primary cells obtained can be AML stem cells or CML stem cells.
56. It is understood and herein contemplated that the known agent of step a can comprise any known to reduce the disease condition. Thus, for example, disclosed herein are methods wherein the known agent is parthenolide (PTL). Also disclosed are methods of identifying a treatment for a disease wherein the known agent is celastrol, 15delta- prostaglandin-J2 (PGJ2), or MG- 132, TDZD-8, and 4-hydroxy-2-nonenal. a) Parthenolide
57. Parthenolide (PTL) is a naturally occurring lactone from Chrysanthemum parthenium. Parthenolide inhibits NF-κB and selectively induces apoptosis in AML stem cells (AML-SCs) but has little to no effect on normal stem cells. Additionally, PTL sensitizes cancer cells to other antitumor agents and acts as a chemopreventive agent in a UVB-induced skin cancer animal model. PTL is a potent inhibitor of NF-κB activation and has been shown to directly bind IκB-kinase (IKK) and to modify the p50 and p65 NF-κB subunits. PTL can also block signal transducers and activators of transcription 3 (STAT3) phosphorylation on Tyr705, sustain c-Jun N-terminal kinase (INK) activation, and increase intracellular reactive oxygen species (ROS). Although a potent chemotherapeutic, PTL has a short half-life and low Cmax, making it unsuitable for use as a pharmaceutical agent. C. Method of treating cancer 58. Disclosed herein are methods of treating a subject with a disease comprising administering to the subject the perturbations identified using the disclosed methods. It is contemplated herein that the disclosed treatments can be used for any known diseases including any cancer disclosed herein. Thus for example, disclosed herein are methods of treating a subject with a disease comprising administering to the subject the perturbations identified using the disclosed methods, wherein the disease is Acute Myeloid Leukemia (AML) or Chronic Myeloid Leukemia.
59. Also disclosed herein are methods of treating AML comprising administering to a subject a thiazolidinedione and a member of the phenothiazine class of psychoactive compounds. It is understood and herein contemplated that any phenothiazine class of psychoactive compounds can be used in the disclosed methods. Therefore, disclosed herein are methods of treatment wherein the phenothizine is chlorpromazine, fiuphenazine, thioridazine, trifluoperazine, or procholoperazine. It is also contemplated herein that the thiazolidinedione can be any member of thiazolidinedione famiy of compositions. For example, the thiazolidinedione can be but is not limited to rosaglitizone, ciglitazone, pioglitazone, or troglitizone. Thus, for example, disclosed herein are methods of treating AML in a subject comprising administering to the subject troglitizone and prochorperazine. 60. It is understood and herein contemplated that one method of treating a disease is to increase the sensitivity of a cell to a known treatment. Thus, for example, disclosed herein are methods of increasing the sensitivity of a disease to a treatment regimen comprising administering to the subject one or more perturbations identified by the disclosed methods. For example, one such method of increasing sensitivity of a disease to a treatment regimen comprises administereing to the subject wortmannin. 1. Chemo therapeutic agents
61. As used herein, "chemotherapeutic agents" refers to those agents that reduce or stop the uncontrolled growth of a cancer cell. Typically such agents can be divided into six groups including Alkylating agents, mitotic disrupters, antimetabolites, cytotoxic antibiotics, topoisomerase inhibitors, and antibodies. Disclosed herein such agents can also include agents such as parthenolide that disrupt one or more necessary pathways. Among the six groups of agents, the mode of action for a particular agent varies. For example, antimetabolites represent the most widely used cytostatics. These agents function by mimicking purines or pyrimidines and subsequently blocking DNA or RNA synthesis. Examples of antimetabolites include but are not limited to Methotrexate, Pemetrexed, Raltitrexed, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Tioguanine, Capecitabine, Cytarabine, Fluorouracil, and Gemcitabine.
62. A second group of chemotherapeutic agents are Alkylating agents which are highly toxic molecules that function by cross-linking DNA through the introduction of alkyl groups into the nucleotide bases. Alkylating agents include but are not limited to agents as Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan; nitrosoureas, for example, Carmustine, Fotemustine, Lomustine, Streptozocin); and platinum containing compounds like Carboplatin, Cisplatin, Oxaliplatin, BBR3464. Alkylating agents also include Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, Uramustine. 63. A third group of chemotherapeutic agents are molecules which disrupt mitosis which affect tubule formation or the stability of micotubules including, for example, Taxane (Docetaxel, Paclitaxel) and Vinca (Vinblastine, Vincristine, Vindesine, Vinorelbine).
64. Chemotherapeutic agents can also include Topoisomerase inhibitors which include but are not limited to Topotecan, Irinotecan, and Podophyllum ( Etoposide,
Teniposide); Cytotoxic/antitumor antibiotics such as Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin, Bleomycin, Hydroxyurea, and Mitomycin; monoclonal antibodies including but not limited to Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Tositumomab, Trastuzumab, and HERCEPTIN (her2/neu); photosensitizers such as, for example, Aminolevulinic acid,
Methyl aminolevulinate, Porfimer sodium, and Verteporfm; and kinase inhibitors, including but not limited to Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib, Vandetanib (ZD6474).
65. Other chemotherapeutic agents include, but are not limited to All-trans retinoic acid, Alitretinoin, Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase,
Bexarotene, Bortezomib, Denileukin diftitox, Estramustine, Hydroxycarbamide, Pentostatin, Masoprocol, Mitotane, Pegaspargase, Tretinoin, adriamycin, Azacitidine, Azathioprine, Bleomycin, Cyclophosphamide, Doxifluridine, Epothilone, Etoposide, Fluoro_uracil, Hydroxyurea, Mechlorethamine, Mercaptopurine, Methotrexate, Pemetrexed, Procarbazine, prednisone, Teniposide, Tioguanine, Parthenolide, Celastrol, Troglitazone, and Prochloroperazine
D. Compositions
66. Disclosed are the components to be used to prepare the disclosed compositions as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods. 1. Nucleic acids
67. There are a variety of molecules disclosed herein that are nucleic acid based as well as any other proteins disclosed herein, as well as various functional nucleic acids. The disclosed nucleic acids are made up of for example, nucleotides, nucleotide analogs, or nucleotide substitutes. Non-limiting examples of these and other molecules are discussed herein. It is understood that for example, when a vector is expressed in a cell, that the expressed mRNA will typically be made up of A, C, G, and U. Likewise, it is understood that if, for example, an antisense molecule is introduced into a cell or cell environment through for example exogenous delivery, it is advantagous that the antisense molecule be made up of nucleotide analogs that reduce the degradation of the antisense molecule in the cellular environment. a) Nucleotides and related molecules
68. A nucleotide is a molecule that contains a base moiety, a sugar moiety and a phosphate moiety. Nucleotides can be linked together through their phosphate moieties and sugar moieties creating an internucleoside linkage. The base moiety of a nucleotide can be adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil- 1-yl (U), and thymin-1-yl (T). The sugar moiety of a nucleotide is a ribose or a deoxyribose. The phosphate moiety of a nucleotide is pentavalent phosphate. An non-limiting example of a nucleotide would be 3'- AMP (3'-adenosine monophosphate) or 5'-GMP (5'-guanosine monophosphate).
69. A nucleotide analog is a nucleotide which contains some type of modification to either the base, sugar, or phosphate moieties. Modifications to nucleotides are well known in the art and would include for example, 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, and 2-aminoadenine as well as modifications at the sugar or phosphate moieties.
70. Nucleotide substitutes are molecules having similar functional properties to nucleotides, but which do not contain a phosphate moiety, such as peptide nucleic acid (PNA). Nucleotide substitutes are molecules that will recognize nucleic acids in a Watson- Crick or Hoogsteen manner, but which are linked together through a moiety other than a phosphate moiety. Nucleotide substitutes are able to conform to a double helix type structure when interacting with the appropriate target nucleic acid. 71. It is also possible to link other types of molecules (conjugates) to nucleotides or nucleotide analogs to enhance for example, cellular uptake. Conjugates can be chemically linked to the nucleotide or nucleotide analogs. Such conjugates include but are not limited to lipid moieties such as a cholesterol moiety. (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989,86, 6553-6556), 72. A Watson-Crick interaction is at least one interaction with the Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute. The Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute includes the C2, Nl, and C6 positions of a purine based nucleotide, nucleotide analog, or nucleotide substitute and the C2, N3, C4 positions of a pyrimidine based nucleotide, nucleotide analog, or nucleotide substitute.
73. A Hoogsteen interaction is the interaction that takes place on the Hoogsteen face of a nucleotide or nucleotide analog, which is exposed in the major groove of duplex DNA. The Hoogsteen face includes the N7 position and reactive groups (NH2 or O) at the C6 position of purine nucleotides. b) Sequences
74. There are a variety of sequences disclosed herein that are disclosed on Genbank, and these sequences and others are herein incorporated by reference in their entireties as well as for individual subsequences contained therein.
75. A variety of sequences are provided herein and these and others can be found in Genbank, at www.pubmed.gov. Those of skill in the art understand how to resolve sequence discrepancies and differences and to adjust the compositions and methods relating to a particular sequence to other related sequences. Primers and/or probes can be designed for any sequence given the information disclosed herein and known in the art. c) Primers and probes 76. Disclosed are compositions including primers and probes, which are capable of interacting with the genes disclosed herein. In certain embodiments the primers are used to support DNA amplification reactions. Typically the primers will be capable of being extended in a sequence specific manner. Extension of a primer in a sequence specific manner includes any methods wherein the sequence and/or composition of the nucleic acid molecule to which the primer is hybridized or otherwise associated directs or influences the composition or sequence of the product produced by the extension of the primer. Extension of the primer in a sequence specific manner therefore includes, but is not limited to, PCR, DNA sequencing, DNA extension, DNA polymerization, RNA transcription, or reverse transcription. Techniques and conditions that amplify the primer in a sequence specific manner are preferred. In certain embodiments the primers are used for the DNA amplification reactions, such as PCR or direct sequencing. It is understood that in certain embodiments the primers can also be extended using non-enzymatic techniques, where for example, the nucleotides or oligonucleotides used to extend the primer are modified such that they will chemically react to extend the primer in a sequence specific manner. Typically the disclosed primers hybridize with the nucleic acid or region of the nucleic acid or they hybridize with the complement of the nucleic acid or complement of a region of the nucleic acid. d) Functional Nucleic Acids
77. Functional nucleic acids are nucleic acid molecules that have a specific function, such as binding a target molecule or catalyzing a specific reaction. Functional nucleic acid molecules can be divided into the following categories, which are not meant to be limiting. For example, functional nucleic acids include antisense molecules, aptamers, ribozymes, triplex forming molecules, and external guide sequences. The functional nucleic acid molecules can act as affectors, inhibitors, modulators, and stimulators of a specific activity possessed by a target molecule, or the functional nucleic acid molecules can possess a de novo activity independent of any other molecules. 78. Functional nucleic acid molecules can interact with any macromolecule, such as
DNA, RNA, polypeptides, or carbohydrate chains. Thus, functional nucleic acids can interact with the mRNA of a cancer stem cell or the genomic DNA of a cancer stem cell. Often functional nucleic acids are designed to interact with other nucleic acids based on sequence homology between the target molecule and the functional nucleic acid molecule. In other situations, the specific recognition between the functional nucleic acid molecule and the target molecule is not based on sequence homology between the functional nucleic acid molecule and the target molecule, but rather is based on the formation of tertiary structure that allows specific recognition to take place.
79. Antisense molecules are designed to interact with a target nucleic acid molecule through either canonical or non-canonical base pairing. The interaction of the antisense molecule and the target molecule is designed to promote the destruction of the target molecule through, for example, RNAseH mediated RNA-DNA hybrid degradation. Alternatively the antisense molecule is designed to interrupt a processing function that normally would take place on the target molecule, such as transcription or replication. Antisense molecules can be designed based on the sequence of the target molecule. Numerous methods for optimization of antisense efficiency by finding the most accessible regions of the target molecule exist. Exemplary methods would be in vitro selection experiments and DNA modification studies using DMS and DEPC. It is preferred that antisense molecules bind the target molecule with a dissociation constant (kd)less than or equal to 10"6, 10"8, 10"10, or 10"12. A representative sample of methods and techniques which aid in the design and use of antisense molecules can be found in the following non-limiting list of United States patents: 5,135,917, 5,294,533, 5,627,158, 5,641,754, 5,691,317, 5,780,607, 5,786,138, 5,849,903, 5,856,103, 5,919,772, 5,955,590, 5,990,088, 5,994,320, 5,998,602, 6,005,095, 6,007,995, 6,013,522, 6,017,898, 6,018,042, 6,025,198, 6,033,910, 6,040,296, 6,046,004, 6,046,319, and 6,057,437. 80. Aptamers are molecules that interact with a target molecule, preferably in a specific way. Typically aptamers are small nucleic acids ranging from 15-50 bases in length that fold into defined secondary and tertiary structures, such as stem-loops or G-quartets. Aptamers can bind small molecules, such as ATP (United States patent 5,631,146) and theophiline (United States patent 5,580,737), as well as large molecules, such as reverse transcriptase (United States patent 5,786,462) and thrombin (United States patent
5,543,293). Aptamers can bind very tightly with kdS from the target molecule of less than 10"12 M. It is preferred that the aptamers bind the target molecule with a k<j less than 10"6, 10"8, 10"10, or 10'12. Aptamers can bind the target molecule with a very high degree of specificity. For example, aptamers have been isolated that have greater than a 10000 fold difference in binding affinities between the target molecule and another molecule that differ at only a single position on the molecule (United States patent 5,543,293). It is preferred that the aptamer have a kd with the target molecule at least 10, 100, 1000, 10,000, or 100,000 fold lower than the k<j with a background binding molecule. It is preferred when doing the comparison for a polypeptide for example, that the background molecule be a different polypeptide. Representative examples of how to make and use aptamers to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,476,766, 5,503,978, 5,631,146, 5,731,424 , 5,780,228, 5,792,613, 5,795,721, 5,846,713, 5,858,660 , 5,861,254, 5,864,026, 5,869,641, 5,958,691, 6,001,988,
6.011.020, 6,013,443, 6,020,130, 6,028,186, 6,030,776, and 6,051,698.
81. Ribozymes are nucleic acid molecules that are capable of catalyzing a chemical reaction, either intramolecularly or intermolecularly. Ribozymes are thus catalytic nucleic acid. It is preferred that the ribozymes catalyze intermolecular reactions. There are a number of different types of ribozymes that catalyze nuclease or nucleic acid polymerase type reactions which are based on ribozymes found in natural systems, such as hammerhead ribozymes, (for example, but not limited to the following United States patents: 5,334,711, 5,436,330, 5,616,466, 5,633,133, 5,646,020, 5,652,094, 5,712,384, 5,770,715, 5,856,463, 5,861,288, 5,891,683, 5,891,684, 5,985,621, 5,989,908, 5,998,193, 5,998,203, WO 9858058 by Ludwig and Sproat, WO 9858057 by Ludwig and Sproat, and WO 9718312 by Ludwig and Sproat) hairpin ribozymes (for example, but not limited to the following United States patents: 5,631,115, 5,646,031, 5,683,902, 5,712,384, 5,856,188, 5,866,701, 5,869,339, and 6,022,962), and tetrahymena ribozymes (for example, but not limited to the following United States patents: 5,595,873 and 5,652,107). There are also a number of ribozymes that are not found in natural systems, but which have been engineered to catalyze specific reactions de novo (for example, but not limited to the following United States patents: 5,580,967, 5,688,670, 5,807,718, and 5,910,408). Preferred ribozymes cleave RNA or DNA substrates, and more preferably cleave RNA substrates. Ribozymes typically cleave nucleic acid substrates through recognition and binding of the target substrate with subsequent cleavage. This recognition is often based mostly on canonical or non-canonical base pair interactions. This property makes ribozymes particularly good candidates for target specific cleavage of nucleic acids because recognition of the target substrate is based on the target substrates sequence. Representative examples of how to make and use ribozymes to catalyze a variety of different reactions can be found in the following non-limiting list of United States patents: 5,646,042, 5,693,535, 5,731,295, 5,811,300, 5,837,855, 5,869,253,
5.877.021, 5,877,022, 5,972,699, 5,972,704, 5,989,906, and 6,017,756. 82. Triplex forming functional nucleic acid molecules are molecules that can interact with either double-stranded or single-stranded nucleic acid. When triplex molecules interact with a target region, a structure called a triplex is formed, in which there are three strands of DNA forming a complex dependant on both Watson-Crick and Hoogsteen base-pairing. Triplex molecules are preferred because they can bind target regions with high affinity and specificity. It is preferred that the triplex forming molecules bind the target molecule with a kd less than 10~6, 10"8, 10"10, or 10"12. Representative examples of how to make and use triplex forming molecules to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,176,996, 5,645,985, 5,650,316, 5,683,874, 5,693,773, 5,834,185, 5,869,246, 5,874,566, and 5,962,426.
83. External guide sequences (EGSs) are molecules that bind a target nucleic acid molecule forming a complex, and this complex is recognized by RNase P, which cleaves the target molecule. EGSs can be designed to specifically target a RNA molecule of choice. RNAse P aids in processing transfer RNA (tRNA) within a cell. Bacterial RNAse P can be recruited to cleave virtually any RNA sequence by using an EGS that causes the target RNA:EGS complex to mimic the natural tRNA substrate. (WO 92/03566 by Yale, and Forster and Airman, Science 238:407-409 (1990)).
84. Similarly, eukaryotic EGS/RNAse P-directed cleavage of RNA can be utilized to cleave desired targets within eukarotic cells. (Yuan et al., Proc. Natl. Acad. ScL USA 89:8006-8010 (1992); WO 93/22434 by Yale; WO 95/24489 by Yale; Yuan and Airman, EMBOJ 14:159-168 (1995), and Carrara et al., Proc. Natl. Acad. ScL (USA) 92:2627-2631 (1995)). Representative examples of how to make and use EGS molecules to facilitate cleavage of a variety of different target molecules be found in the following non-limiting list of United States patents: 5,168,053, 5,624,824, 5,683,873, 5,728,521, 5,869,248, and 5,877,162.
2. Pharmaceutical carriers/Delivery of pharamceutical products
85. As described above, the compositions can also be administered in vivo in a pharmaceutically acceptable carrier. By "pharmaceutically acceptable" is meant a material that is not biologically or otherwise undesirable, i.e., the material may be administered to a subject, along with the nucleic acid or vector, without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained. The carrier would naturally be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art.
86. The compositions may be administered orally, parenterally (e.g., intravenously), by intramuscular injection, by intraperitoneal injection, transdermally, extracorporeally, topically or the like, including topical intranasal administration or administration by inhalant. As used herein, "topical intranasal administration" means delivery of the compositions into the nose and nasal passages through one or both of the nares and can comprise delivery by a spraying mechanism or droplet mechanism, or through aerosolization of the nucleic acid or vector. Administration of the compositions by inhalant can be through the nose or mouth via delivery by a spraying or droplet mechanism. Delivery can also be directly to any area of the respiratory system (e.g., lungs) via intubation. The exact amount of the compositions required will vary from subject to subject, depending on the species, age, weight and general condition of the subject, the severity of the allergic disorder being treated, the particular nucleic acid or vector used, its mode of administration and the like. Thus, it is not possible to specify an exact amount for every composition. However, an appropriate amount can be determined by one of ordinary skill in the art using only routine experimentation given the teachings herein.
87. Parenteral administration of the composition, if used, is generally characterized by injection. Iηjectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions. A more recently revised approach for parenteral administration involves use of a slow release or sustained release system such that a constant dosage is maintained. See, e.g., U.S. Patent No. 3,610,795, which is incorporated by reference herein.
88. The materials may be in solution, suspension (for example, incorporated into microparticles, liposomes, or cells). These may be targeted to a particular cell type via antibodies, receptors, or receptor ligands. The following references are examples of the use of this technology to target specific proteins to tumor tissue (Senter, et al., Bioconjugate Chem., 2:447-451, (1991); Bagshawe, K.D., Br. J. Cancer, 60:275-281, (1989); Bagshawe, et al., Br. J. Cancer, 58:700-703, (1988); Senter, et al., Bioconjugate Chem., 4:3-9, (1993); Battelli, et al., Cancer Immunol. Immunother., 35:421-425, (1992); Pietersz and McKenzie, Immunolog. Reviews, 129:57-80, (1992); and Roffler, et al., Biochem. Pharmacol, 42:2062- 2065, (1991)). Vehicles such as "stealth" and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo. The following references are examples of the use of this technology to target specific proteins to tumor tissue (Hughes et al., Cancer Research, 49:6214-6220, (1989); and Litzinger and Huang, Biochimica etBiophysica Acta, 1104:179-187, (1992)). In general, receptors are involved in pathways of endocytosis, either constitutive or ligand induced. These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes. The internalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation. Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration. Molecular and cellular mechanisms of receptor-mediated endocytosis has been reviewed (Brown and Greene, DNA and Cell Biology 10:6, 399-409 (1991)). a) Pharmaceutically Acceptable Carriers
89. The compositions, including antibodies, can be used therapeutically in combination with a pharmaceutically acceptable carrier.
90. Suitable carriers and their formulations are described in Remington: The Science and Practice of Pharmacy (19th ed.) ed. A.R. Gennaro, Mack Publishing Company, Easton, PA 1995. Typically, an appropriate amount of a pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic. Examples of the pharmaceutically- acceptable carrier include, but are not limited to, saline, Ringer's solution and dextrose solution. The pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7.5. Further carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, liposomes or microparticles. It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered. 91. Pharmaceutical carriers are known to those skilled in the art. These most typically would be Standard carriers for administration of drugs to humans, including solutions such as sterile water, saline, and buffered solutions at physiological pH. The compositions can be administered intramuscularly or subcutaneously. Other compounds will be administered according to standard procedures used by those skilled in the art.
92. Pharmaceutical compositions may include carriers, thickeners, diluents, buffers, preservatives, surface active agents and the like in addition to the molecule of choice. Pharmaceutical compositions may also include one or more active ingredients such as antimicrobial agents, antiinflammatory agents, anesthetics, and the like. 93. The pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated. Administration may be topically (including ophthalmically, vaginally, rectally, intranasally), orally, by inhalation, or parenterally, for example by intravenous drip, subcutaneous, intraperitoneal or intramuscular injection. The disclosed antibodies can be administered intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, or transdermally.
94. Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like.
95. Formulations for topical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. 96. Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may be desirable.. 97. Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or base- addition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mono-, di-, trialkyl and aryl amines and substituted ethanolamines. b) Therapeutic Uses 98. Effective dosages and schedules for administering the compositions may be determined empirically, and making such determinations is within the skill in the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms of the disorder are effected. The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage will vary with the age, condition, sex and extent of the disease in the patient, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. For example, guidance in selecting appropriate doses for antibodies can be found in the literature on therapeutic uses of antibodies, e.g., Handbook of Monoclonal Antibodies, Ferrone et al., eds., Noges Publications, Park Ridge, NJ., (1985) ch. 22 and pp. 303-357; Smith et al., Antibodies in Human Diagnosis and Therapy, Haber et al., eds., Raven Press, New York (1977) pp. 365-389. A typical daily dosage of the antibody used alone might range from about 1 μg/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above.
99. Following administration of a disclosed composition, such as an antibody, for treating, inhibiting, or preventing AML, the efficacy of the therapeutic antibody can be assessed in various ways well known to the skilled practitioner. For instance, one of ordinary skill in the art will understand that a composition, such as an antibody, disclosed herein is efficacious in treating or inhibiting AML in a subject by observing that the composition reduces AML or prevents a further increase in tumor size.
100. The compositions that inhibit interactions necessary for malignant cell survival disclosed herein may be administered prophylactically to patients or subjects who are at risk for AML or other leukemia or cancer.
3. Computer readable mediums
101. Disclosed herein are systems for drug discovery comprising: a) a memory, configured for storing a plurality of molecular abundance signatures and datasets; and b) a processor configured for performing steps comprising 1) generating a first molecular abundance profile, 2) generating a second molecular abundance profile, 3) performing a molecular set analysis technique on each of a plurality of molecular abundance signatures, and 4) statistically prioritizing the molecule sets thereby creating a first molecular set signature. It is understood and herein contemplated that molecular set signature refers to the particular molecular sets to which the user has assigned priority for a particular perturbation. Also, it is understood and herein contemplated that the disclosed systems can be encoded in a computer readable medium. Thus, disclosed herein are computer readable media having computer executable instructions embodied thereon for drug discovery comprising a) generating a first molecular abundance profile, b) generating a second molecular abundance profile, c) performing a molecular set analysis technique on each of a plurality of molecular abundance signatures, and d) statistically prioritizing the molecule sets thereby creating a first molecular set signature.
4. Compositions identified by screening with disclosed compositions / combinatorial chemistry a) Combinatorial chemistry 102. The disclosed compositions can be used as targets for any combinatorial technique to identify molecules or macromolecular molecules that interact with the disclosed compositions in a desired way. The nucleic acids, peptides, and related molecules identified using the methods disclosed herein can be used as targets for the combinatorial approaches. 103. It is understood that when using the disclosed compositions in combinatorial techniques or screening methods, molecules, such as macromolecular molecules, will be identified that have particular desired properties such as inhibition or stimulation or the target molecule's function. The molecules identified and isolated when using the disclosed methods are also disclosed.
104. It is understood that the disclosed methods for identifying molecules that inhibit AML can be performed using high through put means. For example, putative inhibitors can be identified using Fluorescence Resonance Energy Transfer (FRET) to quickly identify interactions. The underlying theory of the techniques is that when two molecules are close in space, ie, interacting at a level beyond background, a signal is produced or a signal can be quenched. Then, a variety of experiments can be performed, including, for example, adding in a putative inhibitor. If the inhibitor competes with the interaction between the two signaling molecules, the signals will be removed from each other in space, and this will cause a decrease or an increase in the signal, depending on the type of signal used. This decrease or increasing signal can be correlated to the presence or absence of the putative inhibitor. Any signaling means can be used. For example, disclosed are methods of identifying an inhibitor of the interaction between any two of the disclosed molecules comprising, contacting a first molecule and a second molecule together in the presence of a putative inhibitor, wherein the first molecule or second molecule comprises a fluorescence donor, wherein the first or second molecule, typically the molecule not comprising the donor, comprises a fluorescence acceptor; and measuring Fluorescence Resonance Energy Transfer (FRET), in the presence of the putative inhibitor and the in absence of the putative inhibitor, wherein a decrease in FRET in the presence of the putative inhibitor as compared to FRET measurement in its absence indicates the putative inhibitor inhibits binding between the two molecules. This type of method can be performed with a cell system as well.
105. Combinatorial chemistry includes but is not limited to all methods for isolating small molecules or macromolecules that are capable of binding either a small molecule or another macromolecule, typically in an iterative process. Proteins, oligonucleotides, and sugars are examples of macromolecules. For example, oligonucleotide molecules with a given function, catalytic or ligand-binding, can be isolated from a complex mixture of random oligonucleotides in what has been referred to as "in vitro genetics" (Szostak, TIBS 19:89, 1992). One synthesizes a large pool of molecules bearing random and defined sequences and subjects that complex mixture, for example, approximately 1015 individual sequences in 100 μg of a 100 nucleotide RNA, to some selection and enrichment process. Through repeated cycles of affinity chromatography and PCR amplification of the molecules bound to the ligand on the column, Ellington and Szostak (1990) estimated that 1 in 1010 RNA molecules folded in such a way as to bind a small molecule dyes. DNA molecules with such ligand-binding behavior have been isolated as well (Ellington and Szostak, 1992; Bock et al, 1992). Techniques aimed at similar goals exist for small organic molecules, proteins, antibodies and other macromolecules known to those of skill in the art. Screening sets of molecules for a desired activity whether based on small organic libraries, oligonucleotides, or antibodies is broadly referred to as combinatorial chemistry. Combinatorial techniques are particularly suited for defining binding interactions between molecules and for isolating molecules that have a specific binding activity, often called aptamers when the macromolecules are nucleic acids.
106. There are a number of methods for isolating proteins which either have de novo activity or a modified activity. For example, phage display libraries have been used to isolate numerous peptides that interact with a specific target. (See for example, United States Patent No. 6,031 ,071 ; 5,824,520; 5,596,079; and 5,565,332 which are herein incorporated by reference at least for their material related to phage display and methods relate to combinatorial chemistry)
107. A preferred method for isolating proteins that have a given function is described by Roberts and Szostak (Roberts R. W. and Szostak J. W. Proc. Natl. Acad. Sd. USA, 94(23)12997-302 (1997). This combinatorial chemistry method couples the functional power of proteins and the genetic power of nucleic acids. An RNA molecule is generated in which a puromycin molecule is covalently attached to the 3 '-end of the RNA molecule. An in vitro translation of this modified RNA molecule causes the correct protein, encoded by the RNA to be translated. In addition, because of the attachment of the puromycin, a peptdyl acceptor which cannot be extended, the growing peptide chain is attached to the puromycin which is attached to the RNA. Thus, the protein molecule is attached to the genetic material that encodes it. Normal in vitro selection procedures can now be done to isolate functional peptides. Once the selection procedure for peptide function is complete traditional nucleic acid manipulation procedures are performed to amplify the nucleic acid that codes for the selected functional peptides. After amplification of the genetic material, new RNA is transcribed with puromycin at the 3 '-end, new peptide is translated and another functional round of selection is performed. Thus, protein selection can be performed in an iterative manner just like nucleic acid selection techniques. The peptide which is translated is controlled by the sequence of the RNA attached to the puromycin. This sequence can be anything from a random sequence engineered for optimum translation (i.e. no stop codons etc.) or it can be a degenerate sequence of a known RNA molecule to look for improved or altered function of a known peptide. The conditions for nucleic acid amplification and in vitro translation are well known to those of ordinary skill in the art and are preferably performed as in Roberts and Szostak (Roberts R. W. and Szostak J. W. Proc. Natl. Acad. Sd. USA, 94(23)12997-302 (1997)).
108. Another preferred method for combinatorial methods designed to isolate peptides is described in Cohen et al. (Cohen B.A.,et al., Proc. Natl. Acad. Sd. USA
95(24): 14272-7 (1998)). This method utilizes and modifies two-hybrid technology. Yeast two-hybrid systems are useful for the detection and analysis of protein:protein interactions. The two-hybrid system, initially described in the yeast Saccharomyces cerevisiae, is a powerful molecular genetic technique for identifying new regulatory molecules, specific to the protein of interest (Fields and Song, Nature 340:245-6 (1989)). Cohen et al., modified this technology so that novel interactions between synthetic or engineered peptide sequences could be identified which bind a molecule of choice. The benefit of this type of technology is that the selection is done in an intracellular environment. The method utilizes a library of peptide molecules that attached to an acidic activation domain. 109. Using methodology well known to those of skill in the art, in combination with various combinatorial libraries, one can isolate and characterize those small molecules or macromolecules, which bind to or interact with the desired target. The relative binding affinity of these compounds can be compared and optimum compounds identified using competitive binding studies, which are well known to those of skill in the art. 110. Techniques for making combinatorial libraries and screening combinatorial libraries to isolate molecules which bind a desired target are well known to those of skill in the art. Representative techniques and methods can be found in but are not limited to United States patents 5,084,824, 5,288,514, 5,449,754, 5,506,337, 5,539,083, 5,545,568, 5,556,762, 5,565,324, 5,565,332, 5,573,905, 5,618,825, 5,619,680, 5,627,210, 5,646,285, 5,663,046, 5,670,326, 5,677,195, 5,683,899, 5,688,696, 5,688,997, 5,698,685, 5,712,146, 5,721,099, 5,723,598, 5,741,713, 5,792,431, 5,807,683, 5,807,754, 5,821,130, 5,831,014, 5,834,195, 5,834,318, 5,834,588, 5,840,500, 5,847,150, 5,856,107, 5,856,496, 5,859,190, 5,864,010, 5,874,443, 5,877,214, 5,880,972, 5,886,126, 5,886,127, 5,891,737, 5,916,899, 5,919,955, 5,925,527, 5,939,268, 5,942,387, 5,945,070, 5,948,696, 5,958,702, 5,958,792, 5,962,337, 5,965,719, 5,972,719, 5,976,894, 5,980,704, 5,985,356, 5,999,086, 6,001,579, 6,004,617, 6,008,321, 6,017,768, 6,025,371, 6,030,917, 6,040,193, 6,045,671, 6,045,755, 6,060,596, and 6,061,636.
111. Combinatorial libraries can be made from a wide array of molecules using a number of different synthetic techniques. For example, libraries containing fused 2,4- pyrimidinediones (United States patent 6,025,371) dihydrobenzopyrans (United States Patent 6,017,768and 5,821,130), amide alcohols (United States Patent 5,976,894), hydroxy- amino acid amides (United States Patent 5,972,719) carbohydrates (United States patent 5,965,719), l,4-benzodiazepin-2,5-diones (United States patent 5,962,337), cyclics (United States patent 5,958,792), biaryl amino acid amides (United States patent 5,948,696), thiophenes (United States patent 5,942,387), tricyclic Tetrahydroquinolines (United States patent 5,925,527), benzofurans (United States patent 5,919,955), isoquinolines (United States patent 5,916,899), hydantoin and thiohydantoin (United States patent 5,859,190), indoles (United States patent 5,856,496), imidazol-pyrido-indole and imidazol-pyrido- benzothiophenes (United States patent 5,856,107) substituted 2-methylene-2, 3- dihydrothiazoles (United States patent 5,847,150), quinolines (United States patent 5,840,500), PNA (United States patent 5,831,014), containing tags (United States patent 5,721,099), polyketides (United States patent 5,712,146), morpholino-subunits (United States patent 5,698,685 and 5,506,337), sulfamides (United States patent 5,618,825), and benzodiazepines (United States patent 5,288,514). b) Computer assisted drug design
112. The disclosed compositions can be used as targets for any molecular modeling technique to identify either the structure of the disclosed compositions or to identify potential or actual molecules, such as small molecules, which interact in a desired way with the disclosed compositions, gene, gene set, or pathway. The nucleic acids, peptides, genes, enzymes, and related molecules disclosed herein can be used as targets in any molecular modeling program or approach. 113. It is understood that when using the techniques, molecules, such as macromolecular molecules, will be identified that have particular desired properties such as inhibition or stimulation of a pathway or cell. The molecules identified and isolated when using the disclosed methods such as RAGE following microarray analysis, are also disclosed. Thus, one way to isolate molecules that bind a molecule of choice is through rational design. This is achieved through structural information and computer modeling. Computer modeling technology allows visualization of the three-dimensional atomic structure of a selected molecule and the rational design of new compounds that will interact with the molecule. The three-dimensional construct typically depends on data from x-ray crystallographic analyses or NMR imaging of the selected molecule. The molecular dynamics require force field data. The computer graphics systems enable prediction of how a new compound will link to the target molecule and allow experimental manipulation of the structures of the compound and target molecule to perfect binding specificity.
Prediction of what the molecule-compound interaction will be when small changes are made in one or both requires molecular mechanics software and computationally intensive computers, usually coupled with user-friendly, menu-driven interfaces between the molecular design program and the user. 114. Examples of molecular modeling systems are the CHARMm and QUANTA programs, Polygen Corporation, Waltham, MA. CHARMm performs the energy minimization and molecular dynamics functions. QUANTA performs the construction, graphic modeling and analysis of molecular structure. QUANTA allows interactive construction, modification, visualization, and analysis of the behavior of molecules with each other.
115. A number of articles review computer modeling of drugs interactive with specific proteins, such as Rotivinen, et al., 1988 Acta Pharmaceutica Fennica 97, 159-166; Ripka, New Scientist 54-57 (June 16, 1988); McKinaly and Rossmann, 1989 Annu. Rev. Pharmacol. Toxiciol. 29, 111-122; Perry and Davies, QSAR: Quantitative Structure-Activity Relationships in Drug Design pp. 189-193 (Alan R. Liss, Inc. 1989); Lewis and Dean, 1989 Proc. R. Soc. Lond. 236, 125-140 and 141-162; and, with respect to a model enzyme for nucleic acid components, Askew, et al., 1989 J. Am. Chem. Soc. Il l, 1082-1090. Other computer programs that screen and graphically depict chemicals are available from companies such as BioDesign, Inc., Pasadena, CA., Allelix, Lie, Mississauga, Ontario, Canada, and Hypercube, Inc., Cambridge, Ontario. Although these are primarily designed for application to drugs specific to particular proteins, they can be adapted to design of molecules specifically interacting with specific regions of DNA or RNA, once that region is identified.
116. Although described above with reference to design and generation of compounds which could alter binding, one could also screen libraries of known compounds, including natural products or synthetic chemicals, and biologically active materials, including proteins, for compounds which alter substrate binding or enzymatic activity. 5. Compositions with similar funtions
117. It is understood that the compositions disclosed herein have certain functions, such as inhibiting AML or CML through the inhibition of NF-κB. Disclosed herein are certain structural requirements for performing the disclosed functions, and it is understood that there are a variety of structures which can perform the same function which are related to the disclosed structures, and that these structures will ultimately achieve the same result, for example stimulation or inhibition NF-κB. E. Examples 118. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and/or methods claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the disclosure. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in 0C or is at ambient temperature, and pressure is at or near atmospheric.
1. Example 1 a) Results 119. Malignant stem cells initiate myeloid leukemias and are resistant to chemotherapy, thereby representing a likely source of disease persistence and relapse. Given the potential clinical importance of targeting such cells, agents with potential to ablate leukemia stem cells were investigated and it was shown that the naturally occurring compound parthenolide (PTL) efficiently destroys AML stem cells (AML-SCs) in vitro (Guzman, MX. et al. (2005) Blood 105, 4163-9). Based on the success of PTL, the gene expression profile of PTL-induced cell death was utilized as a molecular template to predict drug activities/interactions that mediate selective ablation of AML-SC. Analysis of the PTL expression signature with a combination of gene set analysis and public chemogenomic data (the "Connectivity Map") (Lamb, J. et al. (2006) Science 313, 1929-35) yielded multiple novel agents that selectively target AML-SC and/or synergistically enhance the activity of PTL. In addition, extrapolation of pathway data from the PTL molecular profile identified completely novel drug combinations that selectively eradicate AML-SC. Notably, the compounds identified encompass a diverse range of chemical classes, and were only identified as AML-SC agents via gene expression analysis. Taken together, these studies demonstrate that rational design of therapeutic regimens to target AML-SC is possible based on gene expression profiling and bioinformatic analyses. 120. Current AML treatment involves the use of broadly toxic agents including anthracyclines (e.g. idarubicin and daunorubicin) and nucleoside analogs (e.g. cytarabine; Ara-C), which interfere with DNA replication and synthesis. By targeting cells primarily on the basis of active cell division, these regimens poorly discriminate between normal and malignant cells and cause substantial collateral damage to normal tissues, limiting their use due to toxicity especially in the elderly. Importantly, it was shown that AML-SCs are largely refractory to current chemotherapeutics (Guzman, M.L. & Jordan, CT. (2004) Cancer Control 11, 97-104; Guzman, M.L. et al. (2002) Pr oc Natl Acad Sd USA 99, 16220-5), thus representing a likely reservoir of malignant cells in disease relapse.
121. Previous efforts to target these cells lead to the discovery that AML-SCs demonstrate constitutive activation of NF-κB (Guzman, M.L. et al. (2001) Blood 98, 2301- 7) relative to their normal counterparts. Taking advantage of this difference it was discovered found that a NF-κB inhibitor, parthenolide (PTL), can as a single agent selectively induce apoptosis in AML stem, progenitor, and blast cells but not normal hematopoietic cells (Guzman, M.L. et al. (2005) Blood 105, 4163-9). Interestingly, specific molecular genetic inhibition of NF-κB by a transduced dominant negative form of its natural repressor, IKB, generated a substantial albeit less robust cell death response in primary AML (Guzman, M.L. et al. (2001) Blood 98, 2301-7). This finding suggested that NF-κB inhibition is important but insufficient to mediate the full effects of this compound. Although PTL demonstrates highly desirable therapeutic attributes such as specificity, AML-SC-targeting, and low toxicity in vitro, its potential for clinical translation is diminished by undesirable pharmacokinetic attributes such as low Cmax (0.2 μM) and short half-life. Thus, gene expression microarrays were used to generate a molecular template for identifying therapies that potentiate and/or recapitulate the effects of PTL.
122. To this end, primitive CD34+ cells were isolated from 12 primary AML specimens and cultured them in vitro with PTL or vehicle for 1 or 6 hours. Gene expression profiles were obtained using Affymetrix HG-Ul 33 Plus 2.0 microarrays and selected differentially expressed genes (p < 0.01) that were also present in pathways (gene sets) determined to be significant using a gene set enrichment analysis (GSEA) based approach (Subramanian, A. et al. (2005) Proc Natl Acad Sd USA 102, 15545-50 referred to here as Robust Analysis of Geneset Expression or RAGE; see methods). Resulting gene sets observed at 1 and 6 hours are indicated in Table 2 and include genes involved in the heat shock, eIF2, interferon, and NF-κB pathways.
Table 2.
Pathways identified by RAGE-RankProd ordered by significance across 12 AML PTL vs. vehicle comparisons. Top 10 pathways are shown for upregulated and downregulated gene sets at 1 h and 6 h post- treatment. The estimated maximum percent false positive rate (pfp), or false discovery rate, is indicated below each list.
Figure imgf000128_0001
The ability to detect the coordinated downregulation of NF-κB-controlled genes both confirmed the ability to capture the biology of PTL treatment and validated the utility and accuracy of the RAGE gene set analysis approach.
123. To test whether pharmacological perturbation of proteins detected by RAGE could serve to modulate the effects of PTL, eIF5 (of the eIF2 gene set) was chosen as a novel "druggable" target found amongst the pathways in Table 2. The eIF5 protein is among several translation factors differentially upregulated by PTL and is a reported marker for aberrant proliferation as well as a recently proposed cancer target (Cracchiolo, B.M. et al. (2004) Gynecol Oncol 94, 217-22; Jasiulionis, M.G. et al. (2007) Cell Biochem Funct 25, 109-114; Balabanov, S. et al. (2006) Blood). Recent studies have found that eIF5 inhibition sensitizes K562 cells to imatinib. Moreover, it is uniquely regulated by hypusination (Schnier, J., et al. (199I) Mo/ CellBiol W, 3105-14). To assess its potential as a target in novel anti-AML-SC therapy, the PTL-mediated upregulation of eIF5 was antagonized using the antifungal therapeutic, ciclopirox, which is a potent deoxyhypusine hydroxylase inhibitor (Clement, P.M., et al. (2002) Int J Cancer 100, 491-8). hi primary AML cells both ciclopirox and low concentrations of PTL alone had a negligible effect on viability, while the combination of both agents sharply reduced mean viability (Figure IA). Analysis of CD34+/CD38- cells showed that the drug effects were also apparent in highly primitive populations and selective to AML, but not normal cells (Figure IB). This selectivity was also apparent for total CD34+ cells (Figure 4). Additionally the effects of the ciclopirox/PTL combination on primitive progenitor cells by assessing colony forming ability (Fig. 1C) was determined. AML colony forming units (CFUs) were almost completely eradicated (less than 4% of vehicle control), whereas normal CFUs were only modestly reduced by drug treatment (-70% of vehicle control). Together, these observations show that molecular pathway analysis successfully identified a drugable target, eIF5, which may be useful for enhancing the selective ablation primitive AML cells.
124. To broaden the use of the PTL-induced gene expression signature, newly available chemogenomic expression data for 453 treatment-control pairs ("instances") representing 164 unique compounds found in the "Connectivity Map" (CMap)2 we accessed and queried for drug profiles "connected" to the PTL-mediated AML cell death signature using two independent approaches. First, connectivity scores (CS) of PTL to other expression profiles were derived as described (Lamb, J. et al. (2006) Science 313, 1929-35). Briefly, positively connected drugs demonstrate a similar expression profile to PTL whereas negatively connected drugs demonstrate an opposite expression profile, i.e., PTL upregulated genes are downregulated (Table 3a-b).
Figure imgf000129_0001
Figure imgf000130_0001
Second, the Random Forests machine learning algorithm (Breiman, L. (2001) Machine
Learning 45, 5-32) was trained with the expression data on CD34+ AML PTL treatment vs. control pairs to distinguish "PTL-like" drugs. The 453 drug treatment instances of the
CMap were subsequently used as an independent test set upon which to search for PTL-like drugs (Table 4).
Table 4.
"PTL-like" instances as selected by Random Forests classifier.
Figure imgf000130_0002
Nearly all drugs predicted to be "PTL-like" using the Random Forests approach were also found to have the best positive CS, further validating the CS approach and indicating robustness across methods.
125. The initial focus was on drugs identified by both approaches: celastrol, MG- 132, 15-delta-prostaglandin-J2 (PGJ2), monorden, and 17-allylamino-geldanamycin (17-
AAG). MG- 132 and PGJ2 work alone and/or in combination with other agents to produce AML-SC-specific cell death, providing immediate validation of some findings (Guzman, M.L. et al. (2005) Blood 105, 4163-9; Guzman, MX. et al. (2002) Proc Natl Acad Sd USA 99, 16220-5). Monorden and geldanamycin compounds (Whitesell, L. & Lindquist, S.L. (2005) Nat Rev Cancer 5, 761-72) are Hsp90 inhibitors; a target found above by RAGE approach (Table 2). While both agents induce death of primitive AML cells, they are equally toxic to normal progenitors in vitro and were not pursued further. Celastrol however, also an Hsp90 inhibitor (Hieronymus, H. et al. (2006) Cancer Cell 10, 321-30), shares activity and structure with PTL, inhibiting IKB kinase and belonging to the terpenoid class of compounds (Lee, J.H. et al. (2006) Biochem Pharmacol 72, 1311-21; Crombie, L. (1980) Bull Narc 32, 37-50). Given these commonalities, the ability of celastrol to selectively ablate AML and found that it mimicked PTL-like selectively. Primitive CD34+CD38- AML cells treated with 2 μM celastrol for 24 h demonstrated only 13% mean viability compared to 82% for their normal counterparts (Figure 2A). Similar selectivity was noted for AML progenitor cells (Figure 2B). Thus, bioinformatic analysis of the CMap yielded a compound, celastrol, with anti-AML properties almost identical to PTL.
126. Drugs identified by high positive CS or Random Forest classification were largely AML-specific. However, to extend the analysis of drugs that may beneficially interact with PTL, drugs showing negative connectivity to PTL-mediated AML cell death were also explored. Negatively connected instances were highly enriched with drugs acting in the PI3 kinase pathway: rapamycin(Wiederrecht, GJ. et al. (1995) Prog Cell Cycle Res 1, 53-71), LY-294002(Vlahos, CJ., et al. (1994) J Biol Chem 269, 5241-8), and wortmannin(Bonser, R. W. et al. (1991) Br J Pharmacol 103, 1237-41) (Table 3b). Upon examination, these drugs negatively regulate protective genes that are activated in response to PTL exposure such as heme oxygenase 1 (Prestera, T. et al. (1995). MoI Med 1, 827-37). Since these drugs apparently disable protective responses to PTL, it was reasoned that they should sensitize cells and proceeded to test wortmannin. Indeed, while 5 μM wortmannin showed minimal toxicity to primary AML alone, it sensitized CD34+CD38- AML to a sublethal concentration of PTL with minimal effects on normal cells (Fig. 2C-E).
127. Finally, using RAGE-resamplmg, each of the 453 CMap drug treatment instances was examined and striking commonalities were observed among the top pathways perturbed by celastrol, PGJ2, and MG- 132 ("effective agents"). It was further noted that several unrelated drugs in the CMap perturbed a subset of pathways perturbed by effective agents. An appropriate combination of two such non-obvious compounds can result in "pathway complementation" and recapitulate the ability to specifically target primitive AML cells. Thus, this approach vastly improves the chances of selecting PTL-like drug combinations from the 13,366 possible combinations of 164 drugs in the CMap. The effective agents were observed to perturb similar top gene sets (Table 1) based on expression data for CMap instances of drug treatment.
Table 1.
Top perturbed gene sets for selected CMap instances Gene sets showing general upward transcriptional
Figure imgf000132_0001
The three most significant perturbations included heat shock and cellular senescence pathways for all of the effective drugs and the Cox2 pathway for 2 of the 3 drugs. Though heat shock genes were also commonly upregulated by effective agents, we reasoned this upregulation to be protective and thus not an optimal feature when selecting combinations. Scanning the top three perturbed pathways in all other CMap instances, several drugs were identified that shared some common gene sets with the effective agents. Among these compounds were the diabetes drug troglitizone ( Fujiwara, T., et al. (1988) Diabetes 37, 1549-58) and members of the phenothiazine class of psychoactive compounds, from which prochlorperazine ( Stevenson, L.E. (1957) Med Ann Dist Columbia 26, 633-6) was selected for further study. Troglitizone was found to perturb the Cox2 gene set and all phenothiazines robustly perturbed the cellular senescence gene sets. Since cellular senescence and Cox2 gene sets are perturbed among effective agents, mixing of the individual compounds was investigated to determine such mixing can recapitulate PTL-like selective toxicity to AML. Troglitazone or prochlorperazine alone had little effect on CD34+CD38- AML cells (mean viability > 89%) and demonstrated somewhat higher toxicity to normal cells (mean viability > 68%). However, substantial selectivity was evident with the prochlorperazine + troglitazone combination, where survival of AML CD34+CD38- and progenitor cells was significantly less relative to normal counterparts (Figure 3A-C, Figure 5). These data indicate that selective targeting of primitive AML cells can be achieved using drugs that achieve "pathway complementation" to target mechanisms central to AML specific death processes. b) Material and Methods.
(1) Compounds, primary tissues, and cell culture.
128. Drugs were obtained from Sigma-Aldrich with exception of PTL, which was obtained from BioMol. Human primary AML was obtained with informed consent. Cord blood and bone marrow cells were either through consenting donors or from the National Disease Research Interchange (NDRI) in accordance with Institutional Review Board policies. Cells were grown at 37°C in serum-free medium as described (Guzman, MX. et al. (2005) 5/Vκκ/ 105, 4163-9).
(2) Isolation of CD34+ AML total RNA.
129. CD34+ AML were isolated using antibody-coupled magnetic bead separation as previously described (Guzman, M.L. et al. (2005) Blood 105, 4163-9). Cells were cultured for 1 h and subsequently treated with 7.5 μM PTL. Total RNA was harvested at either 1 h or 6 h post-treatment using the RNeasy protocol (Qiagen) according to the manufacturer's instructions.
(3) Microarray hybrdization and analysis. 130. Total RNA was amplified according to the RiboSPIA protocol (NuGen) and hybridized to Affymetrix HG-Ul 33 Plus 2.0 chips per manufacturer's recommendations by the University of Rochester Functional Genomics Core Facility. Differential expression analysis was performed using R (http://www.r-project.org/) and BioConductor (http://www.bioconductor.org/). Raw expression data was normalized using Robust Multi- array Averaging (RMA) with quantile normalization (Mzarry, R.A. et al. (2003) Biostatistics 4, 249-64). Differentially expressed probesets were identified using paired t- tests and p-values were adjusted for multiple testing using the Benjamini-Hochberg procedure.
(4) Robust Analysis of Geneset Expression (RAGE).
131. RAGE is an in-house R package related to the knowledge-based strategy for microarray data analysis proposed by Subramanian and colleagues (Subramanian, A. et al. (2005) Proc Natl Acad Sd USA 102, 15545-50) and adapted here to both multiple sample and single pair inference. For multiple sample inference (e.g. 12 AML PTL-control pairs), a robust average of treatment-control differences of genes in each gene set is calculated followed by rank product analysis implemented in RankProd (Hong, F. et al. (2006) Bioinformatics 22, 2825-7) of the resulting robust averages, this method is termed "RAGE- RankProd". For single pair inference, such as for each CMap instance, RAGE computes a robust average of treatment-control differences for each gene in a gene set and then samples equal sized gene sets consisting of random genes from each pairwise comparison to compute relative significance per sample. Gene sets were derived from MSigDb 1.0 (http://www.broad.mit.edu/gsea/msigdb/msigdb_index.html) as well as from the SuperArray website (SuperArray Bioscience Corporation) and are provided as Supplementary Data.
(5) Acquisition and query of CMap data.
132. The top 100 Affymetrix probesets that were either increased or decreased with 6 h PTL treatment relative to untreated control were used as a query signature and submitted for connectivity score analysis (http://www.broad.mit.edu/cmap). For classification, CMap expression data was obtained from NCBI's Gene Expression Omnibus (http://www.ncbi.nhn.nih.gov/geo/), accession number GSE5258. Random Forests classification was performed to classify "PTL-like" instances and was trained on PTL expression data consisting of 6 primary CD34+ AML 6 h PTL treatment vs. control rank- transformed instances as well as non-PTL expression data consisting of 6 rank-transformed instances of primary CD34+ AML vehicle-treated pairs. The trained classifier was deployed on the rank-transformed CMap to classify each CMap instance.
(6) Cell viability assays. 133. Cells are stained using Annexin V-FITC and 7-aminoactinomycin (7- AAD) to detect phosphatidylserine exposition and cell permeability, respectively, as described (Guzman, MX. et al. (2005) Blood 105, 4163-9). Cells were additionally stained with antibodies against phenotypic markers CD34 and CD38 to assess viability in phenotypically defined subpopulations. At least 50,000 events were recorded per condition on an LSR II flow cytometer (BD Biosystems). Data analysis was conducted using Flow Jo 8.2 software (Mac OS X; Treestar). Cells that are negative for Annexin V and 7-AAD are scored as viable.
(7) Colony forming unit assays. 134. Methycellulose culture assays were used to assess the colony forming ability of both AML and normal hematopoietic progenitors. Growth conditions and scoring were performed as described (Guzman, M.L. et al. (2005) Blood 105, 4163-9) in the presence or absence of drugs.
(8) Expression profiling and analysis. 135. CD34+ AML cells were processed in pairs such that each PTL treatment- control pair (one pair per patient) was treated with the same PTL aliquot after 1 h in culture. Each patient sample was further processed in the same RNA isolation, labeling, and hybridization batch to minimize non-biological variability within pairs. All data used in this study was preprocessed using RMA with quantile normalization. Analysis was conducted using R 2.3.1 with BioConductor 1.8 on Mac OS X 10.4 (PPC).
(9) Robust Analysis of Geneset Expression (RAGE). 136. Log ratios for each probeset were computed for each treatment-control pair.
A single GMT file consisting of gene sets derived from MSigDB 1.0 and from the SuperArray website was read in by RAGE. This file consists of a gene set name and description followed by several gene symbols sharing a biological relationship defined a priori. The gene sets added to MSigDB 1.0 are available as Supplementary Data. Gene sets that consisted of less than 5 genes or more than 100 genes were not considered for analysis. In cases where more than a single Affymetrix identifier could be mapped to a gene symbol, the value of the gene symbol was taken to be the median of all Affymetrix identifiers corresponding to that gene symbol as mapped by the BioConductor hgul33plus2 annotation package. For each pair, a robust average of the log ratios for each gene symbol in a gene set was taken by computing 1-step Tukey's biweight with the tuning constant, c, equal to 5 and episilon equal to 1 x 10"4, though any robust summary statistic maybe applied at this point such as the median. The function for computing Tukeys biweight was taken from the affy BioConductor package. The result is a matrix of n gene sets x p treatment-control pairs. For inference across multiple pairs (several patients), the resulting matrix was submitted for analysis by the RankProd package with num.perm = 500 and cl equal to a vector denoting a single class. The above procedure was applied to the microarray expression data arising from the 12 CD34+ AML PTL treatment-control pairs used in this study. Where biological replicates were not necessarily available, as in the CMap, robust averages were computed per gene set as above for every treatment-control pair (or "instance"). The relative significance of each gene set of size S within an instance was computed by sampling without replacement B random gene sets of size S to estimate the mean and variance of a Gaussian distribution of random gene sets, from which two-sided p- values were computed. This resampling was repeated for each new gene set size S. The value B was set to 400. A gene symbol that is not common both to the gene expression microarray data and gene set was not considered for analysis. If exclusion of the gene symbol from the gene set resulted in a gene set size that is outside the specified minimum and maximum gene set size parameters, the gene set was not analyzed. The sampling data for each gene set of size S was saved to memory if no sampling data for a gene set of size S was previously encountered. When encountering a new gene set of size S, the saved sampling data was retrieved instead of performing a new sampling in order to save time. This analysis was applied to each of the 453 CMap instances.
(10) Processing and Analysis of CMap Data.
137. Connectivity scores to PTL were derived through direct query of the CMap website (http://www.broad.mit.edu/cmap). The query signature consisted of the 100 most upregulated and downregulated probesets relative to vehicle controls following 6 h PTL treatment that were in common between HG-Ul 33 A and HG-Ul 33 Plus 2.0 chips. For classification, CMap expression data consisting of 564 CEL files was downloaded from NCBI's Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/), accession number GSE5258. Data was normalized using RMA with quantile normalization. Covariate information was extracted from the GEO repository using GEOquery (BioConductor) and drug treatments were paired to untreated controls as indicated by Lamb and colleagues to generate 453 treatment-control instances for downstream analysis. Redundant Affymetrix identifiers were reduced to unique gene symbols based on BioConductor hgul33a annotation, using median probeset log ratios when a many-to-one relationship existed between probesets and gene symbols. The same probeset to gene symbol reduction was applied to the training data. All data was rank-transformed prior to training and classification. CMap data was classified using the R implementation of Random Forests applying default parameters.
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Claims

V. CLAIMSWhat is claimed is:
1. A method for identifying a treatment comprising one or more perturbatons having anti- cancer activity comprising a. obtaining one or more first cells, b. obtaining one or more second cells, wherein the second cell has been subject to a modification to differ from the first cell, c. performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d. performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e. performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f. identifying perturbations that modulate the molecular abundance of one or more molecule sets, g. selecting combinations of perturbations wherein each perturbation modulates at least one molecule set arising from the comparison of the first and second cells, and h. testing whether the combination of perturbations recapitulates the desired biological outcome arising from the comparison of the first and second cells.
2. The method of claim 1 , further comprising preselecting molecules prior to analysis.
3. The method of claim 1, further comprising one or more third, fourth, fifth, sixth, or seventh cells.
4. The method of claim 1 , wherein the first cell is a primary cell.
5. The method of claim 1, wherein the cell is a cell line.
6. The method of claim 1 , wherein the first cell is a cancerous cell.
7. The method of claim 5, wherein the cancerous cell is from a cancer cell line.
8. The method of claim 1, wherein first cell is derived from a cancer is selected form the group of cancers consisting of lymphoma, B cell lymphoma, T cell lymphoma, mycosis fungoides, Hodgkin's Disease, leukemias, myeloid leukemia, bladder cancer, brain cancer, nervous system cancer, head and neck cancer, squamous cell carcinoma of head and neck, lung cancers such as small cell lung cancer and non-small cell lung cancer, neuroblastoma/glioblastoma, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, liver cancer, melanoma, squamous cell carcinomas of the mouth, throat, larynx, and lung, gastric cancer, colon cancer, cervical cancer, cervical carcinoma, breast cancer, and epithelial cancer, bone cancers, renal cancer, bladder cancer, genitourinary cancer, esophageal carcinoma, large bowel cancer, metastatic cancers hematopoietic cancers, sarcomas, Ewing's sarcoma, synovial cancer, soft tissue cancers; and testicular cancer.
9. The method of claim 1, wherein the first cell and the second are cancer stem cells.
10. The method of claim 9, wherein the cancer stem cell is a leukemia stem cell.
11. The method of claim 10, wherein the leukemia stem cell is an acute myeloid leukemia stem cell.
12. The method of claim 1, wherein the second cell is a cancer stem cell, and wherein the modification is a treatment that preferentially affects a cancer stem cell and not a non- cancer cell.
13. The method of claim 1, wherein the molecule set analysis technique is computed by one or more of the techniques consisting oft-test, z-test, Mann- Whitney U test, Kolmogrov- Smirnov two sample test, Wilcoxon rank sum test, Wilcoxon signed-rank test, ANOVA,
Kruskal-Wallis analysis of ranks, WaId- Wolfowitz runs test, Friedman test, sign test, Rank Product analysis RAGE-RankProd, RAGE resampling algorithm, Rankind, Rankrel, contab, oneway, regress, pair, and Significance Analysis of Microarrays (SAM).
14. The method of claim 13, wherein the molecule set analysis technique is computed by RAGE-RankProd.
15. The method of claim 13, wherein the molecule set analysis technique is computed by a RAGE- resampling algorithm.
16. The method of claim 1, wherein the identifying of perturbations which modulate the related set is performed by using data from the Connectivity Map.
17. The method of claim 1, wherein the molecular abundance analysis technique measures gene expression.
18. The method of claim 17, wherein the assay is selected from the group of assays consisting of, Northern analysis, RNAse protection assay, PCR, QPCR, RT-PCR, arrays of RT-PCR, microRNA arrays, exon arrays, genome microarray, low density PCR array, oligo array, SAGE and high throughput sequencing.
19. The method of claim 17, wherein the gene expression analysis is performed using a microarray.
20. The method of claim 1, wherein the molecular abundance analysis technique measures protein abundances.
21. The method of claim 20, wherein the assay is selected from the group of assays consisting of protein microarray, antibody-based or protein activity-based assays and mass spectrometry.
22. A method of identifying a treatment for a disease comprising a. comparing the molecular abundance between samples either treated or untreated with an agent known to reduce the disease condition; b. identifying molecules with significant molecular abundance; c. identifying molecules found in significant molecule sets using a molecule set analysis technique; d. identifying perturbations that modulate molecules within molecule sets using a gene expression repository; wherein perturbations that affect said molecules are treatments for the disease.
23. The method of claim 22, wherein the sample is diseased.
24. The method of claim 22, further comprising identifying one or more additional perturbations that affect the same pathway, wherein the perturbations identified in step d individually only affect of subset of pathway of genes involved in the pathway.
25. The method of claim 24, wherein the perturbations have a synergistic effect when used as a treatment.
26. The method of claim 22, wherein the known perturbation is parthenolide (PTL).
27. The method of claim 22, wherein the disease is a blood malignancy.
28. The method of claim 22, wherein the blood malignancy is Acute Myeloid Leukemia (AML) or Chronic Myeloid Leukemia.
29. The method of claim 22, wherein the diseased samples are Acute Myeloid Leukemia Stem Cells (AML SCs) or CML stem cells (CML SCs).
30. The method of claim 22, wherein the samples are primary cells from a subject with AML or CML.
31. The method of claim 22, wherein the molecule set analysis technique is RAGE- resampling.
32. A method of treating a subject with a disease comprising administering to a subject one or more perturbations identified by claim 22.
33. The method of claim 32, wherein the disease is a blood malignancy.
34. The method of claim 33, wherein the disease is AML or CML.
35. The method of claim 22, wherein the known agent is PTL.
36. The method of claim 35, wherein the agent the negatively regulates protective genes is a form of PI3 kinase pathway inhibitor.
37. The method of claim 36, wherein the PI3 kinase pathway inhibitor is selected from the group consisting of rapamycin, LY-294002, or wortmannin.
38. A method of increasing the sensitivity of a disease to a treatment regimen comprising administering to the subject a perturbation identified in claim 22.
39. The method of claim 38, wherein the perturbation is wortmannin.
40. A method of increasing the sensitivity of a disease to a treatment regimen comprising administering to the subject wortmannin.
41. A method of treating AML comprising administering to a subject a thiazolidinedione and a member of the phenothiazine class of psychoactive compounds.
42. The method of claim 41, wherein the thiazolidinedione is troglitizone.
43. The method of claim 41, wherein the phenothiazine member is prochorperazine.
44. A system for drug discovery comprising: a. a memory, configured for storing a plurality of molecular abundance signatures and datasets; and b. a processor configured for performing steps comprising c. generating a first molecular abundance profile, d. generating a second molecular abundance profile, e. performing a molecular set analysis technique on each of a plurality of molecular abundance signatures, f. statistically prioritizing the molecule sets thereby creating a first molecular set signature.
45. A computer readable medium having computer executable instructions embodied thereon for drug discovery comprising a. generating a first molecular abundance profile, b. generating a second molecular abundance profile, c. performing a molecular set analysis technique on each of a plurality of molecular abundance signatures, d. statistically prioritizing the molecule sets thereby creating a first molecular set signature.
46. A method for identifying a treatment comprising one or more perturbations having anticancer activity comprising a. obtaining one or more first cells, b. obtaining one or more second cells, wherein the second cell is a mutated cell, and wherein the mutated cell arises from a cell similar to the first cell, c. performing a molecular abundance analysis technique on the first cell and second cell producing data sets which quantify the molecular abundances for both the first and second cell, d. performing a molecule set analysis technique on the data sets to measure and statistically prioritize differences between the first and second cells, e. performing a molecule set analysis technique to measure and statistically prioritize molecule set differences for other populations of cells, f. identifying perturbations that modulate the molecular abundance of one or more molecule sets, g. selecting combinations of perturbations wherein each perturbation modulates at least one molecule set arising from the comparison of the first and second cells, and h. testing whether the combination of perturbations recapitulates the desired biological outcome arising from the comparison of the first and second cells.
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