WO2017123161A9 - Inhibition of intracellular growth of mycobacterium species and its applications - Google Patents

Inhibition of intracellular growth of mycobacterium species and its applications Download PDF

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WO2017123161A9
WO2017123161A9 PCT/SG2017/050021 SG2017050021W WO2017123161A9 WO 2017123161 A9 WO2017123161 A9 WO 2017123161A9 SG 2017050021 W SG2017050021 W SG 2017050021W WO 2017123161 A9 WO2017123161 A9 WO 2017123161A9
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ilmn
mycobacterium
sirtuin
tuberculosis
mycobacterium tuberculosis
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PCT/SG2017/050021
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French (fr)
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WO2017123161A1 (en
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Amit Singhal
Catherine Cheng
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Agency For Science, Technology And Research
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis

Definitions

  • the present invention generally relates to the field of microbiology and immunology.
  • the present invention relates to compounds that specifically target and modulate host immune response to control and treat bacterial infections.
  • Antibiotics or antibacterial agents are agents that are used to inhibit the growth or kill bacteria.
  • bacteria can develop resistance to antibiotics or antibacterial agents. Resistance of a bacterium to an antibiotic can range from substantially greater tolerance or reduced susceptibility to completely unaffected by the antibiotics. When a bacterium cannot be controlled or killed by antibiotics or antibacterial agents, the bacteria is able to survive, multiply and cause disease or damages to the hosts despite being in the presence of the antibiotic when such scenario occurs, the bacteria is considered resistant to drug (i.e. drug resistant bacteria). Due to the increased reliance on antibiotics to treat common diseases, antibiotic resistant bacteria are rapidly on the rise. Such antibiotic resistant bacteria have become a significant public health threat.
  • Tuberculosis caused by Mycobacterium tuberculosis
  • Tuberculosis (TB) pathogenesis is driven by a complex interplay between the host immune system and the survival strategies of the bacterium.
  • the ability of, for example, Mycobacterium tuberculosis to persist in protected niches within the body delays the efficacy of current antibiotic therapy, contributing to the emergence of, for example, multi-drug resistant (MDR) strains.
  • MDR multi-drug resistant
  • An effective host immune response is important for the containment of persistent bacterial infections, for example a Mycobacterium tuberculosis infection, and this immune response is closely linked to the metabolic programs of the host.
  • the present invention refers to a method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the method comprises administration of a compound which enhances activity of an NAD + - dependent deacetylase.
  • the present invention refers to use of a compound which enhances activity of an NAD + -dependent deacetylase in the manufacture of a medicament for preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof.
  • FIG. 1 shows data showing that the presence of Mycobacterium tuberculosis infection downregulates SIRTl expression.
  • A shows column graphs of the results of SIRTl mRNA that was assessed by qRT-PCR in Mycobacterium tuberculosis infected THP-1 cells over 72 h. SIRTl expression normalized to GAPDH expression, relative to uninfected cells (UN), is shown.
  • B shows images of a Western blot analysis of SIRTl and GAPDH (control) of Mycobacterium tuberculosis infected THP-1 cells, under the conditions as recited in A.
  • FIG. C shows further column graphs depicting the results of SIRTl mRNA expression, which was assessed in the lungs of Mycobacterium tuberculosis infected mice at different time points post-infection.
  • (E) shows micrograph images of immunostained lung tissue sections of a representative macaque from uninfected; BCG- vaccinated- and unvaccinated Mycobacterium tuberculosis infected group; showing reduced SIRT1 (arrow) in unvaccinated Mycobacterium tuberculosis infected macaques. Nuclear staining - dots in grey. NC - necrotic core of granuloma. Magnification 20x.
  • FIG. 2 shows data illustrating that SIRT1 activators enhance control of Mycobacterium tuberculosis growth.
  • A shows a bar chart comparing Mycobacterium tuberculosis growth after 24 hours in scrambled control (WT) and SIRT1 knock down (SIRTl ⁇ ⁇ ) THP-1 cells, presented as a fold change compared to uninfected cells. Average of three independent experiments is shown.
  • B shows line graphs depicting a difference in Mycobacterium tuberculosis growth after treatment of THP-1 cells with a vehicle control or 100 ⁇ of resveratrol (RES).
  • WT scrambled control
  • SIRTl ⁇ ⁇ SIRT1 knock down
  • FIG. 1 shows a line graph depicting the change in Mycobacterium tuberculosis growth after 24 hours in THP-1 cells treated with different doses of SRT 1720 (SRT).
  • (D) shows line graphs illustrating the difference in Mycobacterium tuberculosis growth after treatment of THP-1 cells with vehicle control or 5 ⁇ of SRT.
  • (E) shows a bar chart depicting the differences in Mycobacterium tuberculosis growth after 24 hours in scrambled control (WT) and SIRTl "7" THP-1 cells treated with either a vehicle control, 5 ⁇ of SRT1720 or 100 ⁇ of resveratrol. Data is presented as fold change relative to control.
  • FIG. F shows multiple line graphs, each showing the growth of different multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (e.g. HN878; W148; CC13; AI10; AH30 and KY) after 72 hours in THP-1 cells treated with either a vehicle control, 100 ⁇ isoniazid (INH), 5 ⁇ SRT1720 or 100 ⁇ RES.
  • MDR multi-drug resistant
  • FIG. 1 shows a scatter plot of genes involved in autophagy that are differentially expressed in Mycobacterium tuberculosis infected THP-1 cells [I] vs uninfected cells [U], and in Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol [R] vs untreated [I].
  • Positive and negative regulators of autophagy shown to be enriched are found in the upper left and lower right quadrants of the scatter plot, respectively, lfc - log fold change.
  • H shows flow cytometry histograms of wild type (WT), scrambled control (NC) or SIRTl "7" THP-1 cells which were infected with Mycobacterium tuberculosis for 3 hours and incubated with or without 5 ⁇ of SRT1720, 100 ⁇ of resveratrol or 200 nM Rapamycin (positive control) for 4 hours, immunolabelled with anti-LC3B and Alexa 647- conjugated goat anti rabbit IgG, and analysed by flow cytometry. Shown is a representative histogram of four independent experiments. These histograms show the intracellular expression level of LC3 in the cells.
  • LC3 indicates an increase of autophagy in the cell population, thereby showing the efficacy of the applied compound in cell killing.
  • (I) shows an image of an immunoblot of WT, NC or SIRTl "7" THP-1 cells which were infected and treated with 5 ⁇ of SRT1720 for 24 hours. The cell lysates were then subjected to immunoblot analysis for LC3 and for GAPDH. LC3 II/LC3 I ratio is indicated. This indicates that SRT1720 treatment induces autophagy in WT and NC cells, and not in SIRTl "7" cells, according to the band shown for LC3 II.
  • FIG. 1 shows fluorescent images of THP-1 cells, which were infected with BCG-GFP for 3 hours and incubated with one of the following: with or without 5 ⁇ SRT1720, 1 ⁇ EX527 (EX; a sirtuin inhibitor) or EX + SRT1720. All samples were then incubated with 500 nM LysoTracker (LTR, a fluorescent dye for labelling and tracking acidic organelles in live cells) for 4 hours before fixation. Scale bar represents 5 ⁇ .
  • LTR LysoTracker
  • FIG. 3 shows data showing that SIRTl activators normalize Mycobacterium tuberculosis induced inflammatory responses.
  • A shows a Circos figure depicting gene ontology (GO) pathways modulated by resveratrol (RES) treatment (24 hours) during Mycobacterium tuberculosis infection.
  • the inner circular bar represents the number of genes in each GO category.
  • the middle circular bar represents the number of genes in particular GO category that were significantly changed upon infection (I (infected) vs. U (uninfected)).
  • the outer circular bar shows the number of genes significantly modulated by resveratrol treatment of the infected cells (R (RES -treated, infected) v I (infected)).
  • FIG. 10 A shows a heat map depicting the comparison of 149 genes from Inflammatory response section (GO:0006954) shown in (A), present within 3062 genes that are modulated by resveratrol (See Fig. 10 A). This heat map displays absolute expression values of the upregulated and downregulated genes in the respective analysis.
  • FIG. C shows line graphs depicting the change in mRNA expression levels of IL6, TNFa, MCP-1, and ILIB (cytokines which are indicative of a presence of an immune response in a subject) in Mycobacterium tuberculosis infected THP-1 cells, untreated (IN - infected) or treated with 5 ⁇ of SRT1720 over a period of 72 hours.
  • IL6, TNFa, MCP-1, and ILIB cytokines which are indicative of a presence of an immune response in a subject
  • (D) shows a bar chart, which shows the estimation of the concentration of the cytokines ⁇ , IL6, and MCP-1, respectively, in the culture supernatant of Mycobacterium tuberculosis infected THP-1 cells at 24 hours post-infection, which had been treated with 5 ⁇ SRT1720 or control (DMSO), as measured by ELISA.
  • (E) shows a line graph depicting decrease in mRNA expression of RelA/p65 upon SRT1720 treatment under the conditions as stated in in (C).
  • (F) shows images of immunoblots of cell lysates from uninfected (UN), LPS (Lipopolysaccharide) (lOO ng/ml) stimulated, and Mycobacterium tuberculosis infected THP-1 cells, either untreated or treated with 5 ⁇ SRT1720 over a period of 72 hours.
  • (G) shows a column graph showing the relative protein band density of RelA/p65 and acetylated RelA/p65, normalized to GAPDH at 72 hours. Acetylated p65 enhances an immune response, so the deacetylation of RelA/p65 will prevent an immune response from occurring.
  • FIG. 1 shows column graphs depicting the effect of SRT1720 treatment on RelA/p65 recruitment to TNFa, ILIB, IL6, and MCP-1 promoters in Mycobacterium tuberculosis infected THP-1 cells.
  • Chromatin immunoprecipitation (ChIP) assays were performed with an antibody against RelA/p65 or control rabbit IgG. Aliquots of chromatin were obtained before (Input) or after IP. Isolated chromatin was quantified by realtime PCR.
  • Data is expressed as the fold change over the levels detected in the uninfected cells after correcting for differences in the amount of starting (input) chromatin material. Representative data from three (C) - (E) and two (F) - (H) independent experiments are shown. Data is expressed as mean + SEM performed in triplicate. *P ⁇ 0.05, **P ⁇ 0.01 is determined using a two tailed Student's t-test.
  • FIG. 4 shows data illustrating that SIRT1 activation reduces Mycobacterium tuberculosis growth in mice.
  • A shows a scatter plot depicting the bacillary load in the lungs of control (WT) and Mac-SIRTl KO mice infected with Mycobacterium tuberculosis on day 21 post-infection. Bar indicates the median.
  • B shows line graphs depicting the change in lung and spleen bacillary load of Mycobacterium tuberculosis infected mice treated with 50 or 100 mg/kg of resveratrol starting 7 days post-infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice.
  • FIG. 1 shows line graphs depicting the change in lung and spleen bacillary load of Mycobacterium tuberculosis infected mice treated with 100 mg/kg of SRT1720 starting 7 days post- infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice.
  • FIG. 5 shows data showing that SIRT1 activation reduces tuberculosis associated tissue pathology and inflammation in mice.
  • A shows light micrographs images of hematoxylin and eosin (H&E) staining of representative lung sections on day 35 postinfection from Mycobacterium tuberculosis infected mice, untreated or treated with 100 mg/kg resveratrol. Scale bar at 4x represents 500 micrometres ( ⁇ ), at 40x represents 50 micrometres ( ⁇ ).
  • AFB Acid fast bacilli. IN - Mycobacterium tuberculosis infected mice, IN+RES - resveratrol treated Mycobacterium tuberculosis infected mice.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control untreated group.
  • FIG. 1 A higher number of acid fast bacilli appears to be present in the control
  • E shows a column graph representing the absolute values of the listed inflammatory chemokines and cytokines from the lungs of Mycobacterium tuberculosis infected mice as in (D), as measured using Luminex.
  • F shows a column graph comparing the change in gene expression between WT (Control) and Mac- SIRT1 KO mice infected with Mycobacterium tuberculosis.
  • FIG. G shows a column graph showing the estimated concentrations of ⁇ , TNFa and MCP-1 in the lung homogenate of mice in (F), as measured by ELISA. Bar lines in (B) and (C) represent the median. Subfigures (D) - (G) are representative of two independent experiments. Data is expressed as mean + SEM. *P ⁇ 0.05, **P ⁇ 0.01 by Mann-Whitney test.
  • Fig. 6 provides data showing that SIRT1 activation modulates the lung myeloid landscape in Mycobacterium tuberculosis infected mice.
  • A shows a scatter plot showing the results of t-distributed stochastic neighbour embedding (tSNE) analysis, which was used to objectively delineate myeloid cell subsets of the lung. Aggregate tSNE dimensionality- reduced single-cell data from lung tissues of analysed mice were plotted and color-coded by the 28 'unsupervised' DensVM clusters. A grouped description of each cluster is indicated. Detailed characterizations of each cluster are described in Fig. 14.
  • tSNE stochastic neighbour embedding
  • FIG. B shows a heat-plot summary of normalized cluster frequency (unsupervised clustering) across the different groups of mice, either untreated or treated with 100 mg/kg SRT 1720.
  • “*” indicates clusters that were significantly altered in IN compared with UN.
  • "+” indicates clusters that were significantly altered in IN+SRT compared with IN.
  • FIG. 15A shows column graphs showing the frequency of CD45 + CD3 " CD90 " CD19 " (Ly6C subsets) in various cell populations as mass cytometry data, analysed by manual gating strategy (detailed in Fig. 15A). MQs - macrophages, DCs - dendritic cells and pDCs - plasmacytoid dendritic cells.
  • D shows further t-distributed stochastic neighbour embedding (tSNE) analysis of cellular composition of lung tissues derived from UN (untreated), IN (infected) and IN+SRT (infected and treated with SRT1720) mice, highlighting six SRT1720 modulated clusters. Each plot represents a pool of 3 to 4 lung tissue cells.
  • tSNE stochastic neighbour embedding
  • Clusters 1, 10, 18, 19, 21, and 23 are shown (circled). Ungrouped cells (remaining) are shown in gray.
  • E shows column graphs depicting the mean frequencies of Ly6C subsets among CD45 + myeloid cells. Mass cytometry data was analysed by traditional gating strategy as in C.
  • F shows scatter plots while
  • G shows histograms depicting the results of fluorescent flow cytometric analysis performed to validate changes in Ly6C lo /Ly6C + monocyte composition observed in the lungs of Mycobacterium tuberculosis infected animals upon SRT1720 treatment.
  • Fig. 7 shows data depicting the SIRT1 expression in Mycobacterium tuberculosis infected human cells and in the peripheral blood of humans infected with Mycobacterium tuberculosis and other diseases.
  • A shows line graphs depicting the changes in RNA expression in THP-1 cells which were infected with Mycobacterium tuberculosis and cultured for 72 hours. RNA extracted from these cells was assessed by microarray. Expression data of SIRT1-SIRT7 mRNA in infected cells change relative to that in uninfected cells are depicted.
  • (B) shows line graphs depicting the expression data of SIRT1 in Mycobacterium tuberculosis infected macrophages from the published dataset GSE51029.
  • (C) shows a line graph representing the expression data of SIRT1 in Mycobacterium tuberculosis infected macrophages from Karim et al. (D) to (G) show the raw data of SIRT1 expression in the peripheral blood of different cohorts, which are Malawi/SA 2013 (D), UK 2010 (E), South Africa 2012 (F) and Viet 2008 (G). These cohorts are of active and latent tuberculosis patients and other diseases in which tuberculosis is a differential diagnosis. Less expression of SIRT1 mRNA were observed in active tuberculosis patients in these cohorts. Bar indicates median. *P ⁇ 0.05, **P ⁇ 0.01 as determined by Mann-Whitney and paired Wilcoxon signed-rank test.
  • FIG. 8 shows data showing that SIRT1 is expressed by CD68/CD163 macrophages in granulomas of Mycobacterium tuberculosis infected macaques.
  • A shows representative confocal images of lung sections of an Mycobacterium tuberculosis infected BCG-vaccinated macaque showing the presence of SIRT1 in CD68/CD163 macrophages and the absence of SIRT1 in CD3 + T cells. Scale bar, 15 ⁇ (Top) or 50 ⁇ (Bottom).
  • B shows a bar graph illustrating the different in percentage expression of CD68/CD163 in SIRT1 + cells.
  • FIG. 9 shows data illustrating the downregulation of SIRTl expression by mycobacteria and control of mycobacterial growth by resveratrol and SRT 1720.
  • A shows a line graph depicting the results of the evaluation of cell viability of THP- 1 cells which were treated with resveratrol (RES) at indicated concentrations for 72 hours.
  • B shows a line graph showing the results of cell viability evaluation of THP-1 cells treated with SRT 1720 under the conditions as stated in A.
  • C shows a line graph depicting the number of BCG in THP-1 cells which survived after 24 hour treatment with different doses of resveratrol (RES).
  • FIG. D shows a column graph depicting the BCG survival in human monocyte-derived macrophages (hMDMs) upon treatment with vehicle control or 5 ⁇ SRT 1720 (SRT) over a 48 hour period of infection.
  • E shows line graphs showing BCG survival in THP-1 cells upon treatment with vehicle control or 100 ⁇ RES in the absence or presence of 1 ⁇ EX527 (EX; a sirtuin inhibitor), over a 48 hour infection period.
  • EX a sirtuin inhibitor
  • FIG. F shows a line graph depicting BCG survival in THP-1 cells upon treatment with vehicle control, 5 ⁇ SRT or 60 ⁇ SA-3 over a 72 hour infection period. Growth of BCG in THP-1 cells is inhibited by treatment with 60 ⁇ SA-3.
  • G shows data illustrating that Mycobacterium tuberculosis infection led to a decrease in NAD + levels in THP- 1 cells and thus decreases NAD + /NADH ratio, while SRT 1720 treatment elevates the NAD + /NADH ratio.
  • (H) shows column graphs depicting the fold change of SIRTl mRNA expression, which was assessed by qRT-PCR in THP-1 cells infected with Mycobacterium tuberculosis, which were either untreated or treated with 5 ⁇ SRT1720 over 72 hours. Relative expression normalized to GAPDH expression and to those of uninfected cells (UN) is shown. Data in (G) are expressed as mean NAD + /NADH ratio of two independent experiments performed in duplicate. All other experiments are carried out in triplicate and are representative of three independent experiments unless stated. *P ⁇ 0.05, as determined using two-tailed Student's t- test.
  • Fig. 10 shows data illustrating that resveratrol modulates the global gene expression during mycobacterial infection.
  • A shows a flow chart depicting the strategy for analysis of microarray data.
  • B shows a scatter plot of genes differentially expressed in the Mycobacterium tuberculosis infected THP-1 cells versus uninfected cells (I vs U), and Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol (RES) versus untreated (R vs I). Expression of 3062 genes overlapped between the two treatments and reversed by RES treatment are shown in quadrant X and Y.
  • FIG. C shows a table listing the results of Ingenuity's pathway analysis (IP A) of 3062 differentially expressed genes (DEGs), thereby indicating the modulation of the pathways by resveratrol (RES) treatment.
  • IP A Ingenuity's pathway analysis
  • DEGs differentially expressed genes
  • RES resveratrol
  • FIG. 11 shows data depicting that SIRT1 activation induces LC3 expression and phagosome-lysosome fusion in mycobacteria infected THP-1 cells.
  • A shows flow cytometry histograms of wild type (WT) THP-1 cells which were infected with GFP conjugated BCG for 3 hours and incubated with either 5 ⁇ of SRT or 100 ⁇ Isoniazid (INH; Positive control) for 4 hours, or which remained untreated, and immunolabelled with anti-LC3B, followed by addition of Alexa 647 -conjugated goat anti rabbit IgG and analyzed by flow cytometry. Representative histogram of two independent experiments is shown.
  • FIG. 1 shows that SRT treatment enhances LC3B expression in Mycobacterium BCG infected cells, whereby isoniazid (INH) is used as a positive control.
  • FIG. 1 shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in THP-1 cells. WT THP-1 cells were infected as in (A) and treated with 5 ⁇ SRT and 500 nM LysoTracker (LTR) for 4 hours before fixation. Quantification of LTR-positive Mycobacterium BCG-GFP is shown.
  • (C) shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in THP-1 cells after 24 hours of treatment.
  • WT THP-1 cells were infected as in (A) and treated with 5 ⁇ SRT or 100 ⁇ RES, and 500 nM LysoTracker (LTR) for 24 hours before fixation. Quantification of LTR- positive BCG-GFP is shown.
  • (D) shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in SIRT1 "7" THP-1 cells. SIRTl "7" THP-1 cells were infected as in (A) and treated with 5 ⁇ SRT and 500 nM LysoTracker (LTR) for 4 hours before fixation. Quantification of LTR-positive BCG-GFP is shown. NS - not significant. *P ⁇ 0.05, by two-tailed Student's t- test.
  • FIG. 12 shows data illustrating that SRT1720 reduces tissue Mycobacterium tuberculosis load, reduces Mycobacterium tuberculosis derived lung pathology and that SIRTl deficient mice display an enhanced inflammatory response.
  • A shows line graphs showing the change in bacillary load in lung and spleen of Mycobacterium tuberculosis infected mice. These mice were treated with 25, 50, or 100 mg/kg of SRT starting 7 days post-infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice.
  • FIG. B shows a column graph depicting the change in SIRTl expression in the lungs of Mycobacterium tuberculosis infected mice which were treated with 25, 50 or 100 mg/kg of SRT1720, starting 7 days post-infection.
  • RNA was extracted and SIRTl mRNA expression was assessed by qRT-PCR. Relative expression differences normalized to GAPDH expression are shown.
  • Data is a representative of two independent experiments. *P ⁇ 0.05 as determined using Student's t- test.
  • FIG. 1 shows images showing the gross appearance of mouse lungs and spleens at day 35 post-infection from Mycobacterium tuberculosis infected mice, either untreated or treated with 100 mg/kg SRT1720 (SRT 100).
  • D shows light micrographs of hematoxylin and eosin staining of lung sections on day 35 after infection from Mycobacterium tuberculosis infected mice, either untreated or treated with lOOmgkg SRT1720 (SRT 100).
  • E shows column graphs depicting change in gene expression between wild type (WT) and Mac-SIRTl KO mice, which were infected with Mycobacterium tuberculosis.
  • RNA was extracted from the peritoneal cells and mRNA expression was assessed by qRT-PCR. Relative expression levels normalized to GAPDH are shown. Data is expressed as mean + SEM. n 4 - 9 mice per group. *P ⁇ 0.05, **P ⁇ 0.01 as determined Mann-Whitney test.
  • Fig. 13 shows various two-parameter dot plots as examples of the staining performed for each antibody used for the mass cytometry analysis. To verify the functionality of each antibody, representative plots illustrating the expected staining profiles of each antibody are shown. Cells gated as shown (as annotated above each plot).
  • Fig. 15 shows scatter plots and histograms outlining the manual gating strategy used in the analyses disclosed above.
  • A shows scatter plots and histograms showing the sequential manual gating strategy of the gathered mass cytometry data in order to annotate the major clusters of lung cells.
  • B shows scatter plots and cell population charts showing the fluorescent flow cytometric gating strategy used to validate changes in monocyte composition in the lungs of Mycobacterium tuberculosis infected mice upon SRT1720 treatment. Similar staining and gating strategy was used to assess the infiltrated myeloid cells in Mycobacterium tuberculosis infected Mac-SIRTl KO mice
  • Fig. 16 shows scatter plots depicting the strategy using in the validation of t- distributed stochastic neighbour embedding (tSNE) guided lung populations.
  • A shows scatter plots depicting the validation of tSNE guided dendritic cell populations.
  • tSNE-guided analysis identified three major subsets of dendritic cell population i.e. Clusters 7, 17 and 29 (refer to Figure 14). These clusters were overlayed on CDl lc + MHCII + gated cells. Cluster 7 and 17 were found to express CDl lb and not CD103, whereas cluster 29 was found to express CD103 and not CDl lb marker. This confirms the authenticity of the clusters.
  • FIG. 14 shows scatter plots depicting the validation of tSNE guided Ly6C l0 lung population.
  • tSNE- guided analysis identify 4 and 5 major subsets of Ly6C l0 and Ly6C + monocyte subsets, respectively (refer to Figure 14).
  • CD1 lc ' MHCIT cells were gated and Ly6C + monocytes (five clusters) and Ly6G + neutrophils were excluded.
  • Ly6C l0 clusters 8, 9, 18 and 19 are shown in bottom left square and ungrouped cells (remaining) are shown in top left and right square.
  • CDl lb expression divides these 4 clusters in two groups with 8 and 9 together and 18 and 19 together.
  • CD44 expression further separates cluster 8 and 9, whereas CD38 expression separates cluster 18 and 19.
  • Fig. 17 shows scatter plots and column graphs depicting the changes in lung myeloid cell population upon Mycobacterium tuberculosis infection and SRT1720 treatment.
  • A shows scatter plots depicting the results of aggregate t-distributed stochastic neighbour embedding (tSNE) dimensionality, whereby reduced single cell data from lung tissues of mice analyzed are plotted and color-coded into the 28 'unsupervised' DensVM clusters.
  • tSNE guided analysis of all four groups Uninfected, infected, infected+SRT and uninfected+SRT is shown. A grouped description of each cluster is indicated.
  • Each plot represents a pool of 3 to 4 replicate lung tissue cells.
  • FIG. 12A shows column graphs depicting mass cytometry data that was analyzed using manual gating strategy (as described in Fig. 12A). Mean frequencies of dendritic cells (CDl lc + MHCII + ) and its subset are shown in the lungs of uninfected (UN), infected (IN) and SRT1720 treated infected (IN+SRT) animals.
  • C shows column graphs depicting the mean frequencies of CD64 + MerTK + macrophages (MQs), alveolar macrophages (AMs, CD64 + MerTK + Siglec_F + ) and Interstitial macrophages (IMs, CD64 + MerTK + Siglec_F ⁇ ) in mass cytometry data.
  • FIG. D shows a bar chart depicting the differential cluster percentage of 6 clusters in uninfected (UN), Infected (IN) and SRT1720 treated infected (IN+SRT) animals. All these 6 clusters are differentially modulated by SRT1720 treatment (P ⁇ 0.05). "*" indicates significance between UN and IN; " + " indicates significance between IN and IN+SRT. Since no differences were found among UN and UN+SRT groups ( Figure 5B), the data of uninfected and uninfected+SRT animals were grouped in a single group for this analysis and considered as uninfected (UN).
  • (E) shows a column graph depicting percentage data of lung Ly6C lo /Ly6C + CDl lb lo F4/80 + monocytes in Mycobacterium tuberculosis infected WT (controls) and Mac-SIRTl KO mice on day 3 postinfection, as assessed using flow cytometry.
  • (F) shows a column graph depicting flow cytometry data indicating percentage of CD45 + CDl lc + lung cells from Mycobacterium tuberculosis infected mice, either treated with SRT1720 or untreated. Data is expressed as mean + SEM.
  • n 4 - 6 mice per group. *P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001, + P ⁇ 0.05 as determined using Mann- Whitney test.
  • the present invention shows that Mycobacterium tuberculosis downregulates sirtuin 1 (SIRT1), a NAD + -dependent deacetylase, in monocytes / macrophages, tuberculosis animal models, and tuberculosis patients with active disease.
  • SIRT1 sirtuin 1
  • Activation of SIRT1 reduced intracellular growth of drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, induced phagosome-lysosome fusion and autophagy in SIRT1 -dependent manner.
  • SIRT1 activation dampened Mycobacterium tuberculosis mediated persistent inflammatory responses via deacetylation of RelA/p65, leading to impaired binding of RelA/p65 on the promoter of inflammatory genes.
  • use of SIRT1 activators ameliorated lung pathology, reduced chronic inflammation and enhanced efficacy of anti-tuberculosis drug.
  • Mass Cytometry based high-dimensional analysis revealed SIRT1 activation mediated modulation of lung myeloid cells in Mycobacterium tuberculosis infected mice.
  • myeloid cell-specific SIRT1 knockout mice display increased inflammatory responses and susceptibility to Mycobacterium tuberculosis infection.
  • SIRTl expression is downregulated during active Mycobacterium tuberculosis infection, and that enhancement of SIRTl activity using specific activators inhibits the intracellular growth of Mycobacterium tuberculosis, normalizes the inflammatory response, enhances the efficacy of other compounds, for example isoniazid, a first-line anti-tuberculosis drug, and limits disease immunopathology.
  • the present invention provides a method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the method comprises administration of a compound which enhances activity of an NAD + -dependent deacetylase.
  • NAD + -dependent deacetylase refers to a class of proteins deacetylases, which are enzymes which have the ability to remove acetyl groups from lysine amino acids in the target proteins, whereby this activity is dependent on the presence or absence of nicotinamide adenine dinucleotide (NAD + ).
  • NAD + - dependent protein deacetylases are, but are not limited to, histone deacetylases (HDACs) These protein deacetylases can be divided into various categories, classes I to IV, of which class III refers to NAD + -dependent protein deacetylases. Examples of class III NAD + - dependent protein deacetylases are, but are not limited to sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, and sirtuin 7.
  • HDACs histone deacetylases
  • sirtuin stands for “silent mating type information regulation 2 homologs”, and refers to a family of nicotinamide adenine dinucleotide (NAD + )- dependent class III histone deacetylases (HDACs), consisting of seven members (for example, sirtuin 1 to sirtuin 7 in humans), which are present in nearly all sub-cellular compartments.
  • NAD + nicotinamide adenine dinucleotide
  • HDACs histone deacetylases
  • sirtuin-mediated deacetylation requires the concomitant reaction of NAD hydrolysis in order to be able to deacetylate lysine, meaning to say that NAD + is used as a co-factor in the reaction.
  • the protein sirtuin 1 (SIRTl) is involved in a range of cellular processes important in the maintenance of human health, including the stress response, cellular metabolism, and ageing. SIRTl is known to be important in the prevention of viral diseases; however, its role in chronic bacterial infections is unknown.
  • sirtuin 2 Cytosolic functions of sirtuin 2 include the regulation of microtubule acetylation, control of myelination in the central and peripheral nervous system and gluconeo genesis.
  • Sirtuin 3, sirtuin 4 and sirtuin 5 are located in mitochondria and regulate metabolic process and enzymes.
  • Sirtuin 6 is a stress responsive protein deacetylase and is essential in post-natal development and survival.
  • Sirtuin 7 localizes to nucleolus and interacts with RNA Polymerase I. Sirtuin 7 can attenuate DNA damage and thereby promote cellular survival under conditions of genomic stress.
  • sirtuins also include, and are not limited to, mono-adenosin triphosphate -ribosyltransferase, or deacylase activity, including desuccinylase, demalonylase, demyristoylase and depalmitoylase activity.
  • the compound is a sirtuin enhancer.
  • the NAD + -dependent deacetylase is, but is not limited to, sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7, derivatives, homologues and combinations thereof.
  • the NAD + - dependent deacetylase is sirtuin 1.
  • the term "homologue” refers to the existence of shared ancestry between genes (or structures) in different taxa.
  • homology is the relationship between biological structures or sequences that are derived from a common ancestor and that ultimately have the same or similar functions (that is a biological equivalent).
  • sequence homology DNA or protein sequences are defined in terms of shared ancestry.
  • sequence homology is often used in place of the term “sequence similarity", or vice versa. Thus, a sequence that is highly conserved (a conservative sequence) if it does not change or only shows minimal changes between the species.
  • SIRTl stands for "sirtuin (silent mating type information regulation 2 homolog) 1 (Saccharomyces cerevisiae)", referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (Saccharomyces cerevisiae) is Sir2.
  • the compounds disclosed herein have the ability to increase the activity of the target proteins, in this case, the NAD + -dependent deacetylase, or, for example, at least one or more sirtuin proteins, that is any one or more of sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7.
  • sirtuin 1 sirtuin 1
  • sirtuin 2 sirtuin 3
  • sirtuin 4 sirtuin 5
  • sirtuin 6 sirtuin 7.
  • SRT1720 specifically enhances SIRTl activity.
  • resveratrol has an effect on SIRTl and SIRT2.
  • the compound SA3 has been shown to affect SIRTl.
  • the compound is, but is not limited to, N-[2-[3-(piperazin-l-ylmethyl)imidazo[2,l-b][l,3]thiazol- 6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N-cyclopentyl-2-diazenyl-l-(3- methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4-phenyl- l,4-dihydro-3,5-pyridinedicarboxylate (BML278), trans-3,5,4'-trihydroxystilbene (resveratrol); and salts and/or derivatives thereof.
  • SA3 N-cyclopentyl-2-diazenyl-l-(3- methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide
  • BML278 diethyl l-benzyl-4
  • the compound is not resveratrol.
  • the compound is, but is not limited to, N-[2-[3-(piperazin-l- ylmethyl)imidazo[2,l-b][l,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N- cyclopentyl-2-diazenyl-l-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4-phenyl-l,4-dihydro-3,5-pyridinedicarboxylate (BML278), and salts and/or derivatives thereof.
  • the compound is N-[2-[3-(piperazin-l- ylmethyl)imidazo[2,l-b][l,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720) or a derivative thereof.
  • a derivative refers to a structural analogue of the compound in question.
  • a derivative can be, but is not limited to, a salt, an isomer, a tautomer, a prodrug or a pharmaceutically accepted version of the compound.
  • Specific methods of the invention further comprise the administration of an additional therapeutic agent (that is, a therapeutic agent other than a compound of the invention) or a further therapy.
  • an additional therapeutic agent that is, a therapeutic agent other than a compound of the invention
  • the compound(s) can be used in combination with at least one other therapeutic agent.
  • the compound(s) can be used in combination with at least one other therapy (also known as combination therapy).
  • the compound(s) can be used in combination with at least one other treatment regime.
  • Therapeutic agents include, but are not limited to antibiotics, anti-emetic agents, anti-depressants, and antifungal agents, anti-inflammatory agents, antiviral agents, anti-cancer agents, anti-microbial agents, anti-tuberculosis agents, immunomodulatory agents, alpha-interferons, ⁇ -interferons, alkylating agents, hormones or cytokines.
  • the invention encompasses administration of at least one or more additional therapeutic agent(s) that demonstrates anti-tuberculosis activity.
  • the combination therapy comprises chemotherapy.
  • the compounds of the invention and the other therapeutics agent can act additively or, preferably, synergistically.
  • a composition comprising a compound disclosed herein is administered concurrently with the administration of another therapeutic agent, which can be part of the same composition or in a different composition from that comprising the compounds of the invention.
  • a compound of the invention is administered prior to, together with, sequentially or subsequent to administration of another therapeutic agent.
  • a compound as disclosed herein is administered to a patient who has not previously undergone or is not currently undergoing treatment with another therapeutic agent.
  • a compound as disclosed herein is administered to a patient who has previously undergone or is currently undergoing treatment with another therapeutic agent.
  • the method, as disclosed herein refers to the administration of one or more compounds, as described herein, without an additional therapeutic agent.
  • mycobacterial refers to infections resulting from an initial infection and the resulting propagation of mycobacteria in a host.
  • Mycobacterium is a genus of bacteria from the family Mycobacteriacea.
  • the bacterial agents from the genus Mycobacterium include, but are not limited to, M. africanum, M. bovis, M. bovis BCG, M. canetti, M. caprae, M. microti, M. mungi, M. orygis, M. pinnipedii, M. suricattae, M.
  • tuberculosis all of which form the so-called Mycobacterium tuberculosis complex, which is a grouping of causative agents of human and animal tuberculosis; as well as M. avium, M. avium paratuberculosis, M. avium silvaticum, M. avium "hominissuis” , M. colombiense, M. indicus pranii, which form the so-called Mycobacterium avium complex; M. asiaticum, M. gordonae, M. gastri, M. kansasii, M. hiberniae, M. nonchromogenicum, M. terrae, M. triviale, M.
  • ulcerans (a known of the "Buruli", or “Bairnsdale” ulcer), M. pseudoshottsii, M. shottsii, M. triplex, M. genavense, M. florentinum, M. lentiflavum, M. palustre, M. kubicae, M. parascrofulaceum, M. heidelbergense, M. interjectum, M. simiae, M. bohemicum, M. botniense, M. branderi, M. celatum, M. chimaera, M. conspicuum, M. cookie, M. doricum, M. farcinogenes, M. haemophilum, M. homeeshornense, M.
  • M. lacus M. leprae (a known cause of leprosy), M. lepraemurium M. lepromatosis (another, less significant, cause of leprosy), M. liflandii, M. malmoense, M. marinum, M. monacense, M. montefiorense , M. murale, M. nebraskense, M. saskatchewanense , M. scrofulaceum, M. shimoidei, M. szulgai, M. tusciae, M. xenopi, M. yongonense, M. intermedium, M. abscessus, M.
  • M. immunogenum M. massiliense, M. moriokaense, M. psychrotolerans, M. pyrenivorans, M. vanbaalenii, M. pulveris, M. arosiense, M. aubagnense, M. chlorophenolicum, M. fluoroanthenivorans, M. kumamotonense, M. novocastrense, M. parmense, M. phocaicum, M. poriferae, M. rhodesiae, M. seoulense, and M. tokaiense, whereby the term "M.” stands for Mycobacterium.
  • Various species and strains can be grouped together, for example, according to the growth rate of the mycobacteria, or according to their microscopic appearance (for example, microbiological characteristics, structural appearances, and staining).
  • the latest approach is to group strains and species using cladistics, which is the classification of organisms based on the group's most recent ancestor in combination with, for example, comprehensive phylogenetic analysis based on genetic alignments of core genomes of bacterial strains.
  • the various species can also be grouped together according to their pathogenicity (for example, pathogenic and non- pathogenic), as well as the diseases which they cause (for example, human and animal tuberculosis is caused by the bacteria listed in the Mycobacterium tuberculosis complex (MTBC)).
  • MTBC Mycobacterium tuberculosis complex
  • the mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium ajricanum, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium leprae, Mycobacterium avium, Mycobacterium paratuberculosis and Mycobacterium pinnipedii.
  • the mycobacterium is a causative agent of tuberculosis.
  • the mycobacterium is a drug -resistant mycobacterium.
  • the mycobacterium is a multidrug-resistant (MDR) or extensively drug- resistant (XDR) mycobacterium.
  • drug-resistance refers to the capability of organisms, usually pathogens, to "acquire" (that is, to evolve) a resistance to the drug used against them, therefore reducing the drug's effectiveness as, for example, an antimicrobial, anti-helminthic or an anti -neoplastic in treating and/or curing a disease or condition caused by said pathogen.
  • MDR multidrug-resistant
  • XDR expressly drug-resistant
  • tuberculosis multi-drug resistant is used to describe a tuberculosis pathogen that is resistant to at least isoniazid and rifampin, at present the two most potent and most commonly prescribed tuberculosis drugs.
  • Extensively drug-resistant tuberculosis is a form of multidrug- resistant tuberculosis which is resistant to isoniazid and rifampin, as well as fluoroquinolone and at least one of three injectable second-line tuberculosis drugs (for example, but not limited to amikacin, kanamycin, or capreomycin).
  • the antituberculosis drug (also known as a tuberculosis drug) can be, but is not limited to, amikacin, aminosalicylic acid, bedaquiline, capreomycin, cycloserine, delamanid ethambutol, ethionamide, fluoroquinolone, fluoroquinolone antibiotic, isoniazid (INH), kanamycin, levofloxacin, linezolid, moxifloxacin, oxafloxacin, (6S)-2-nitro-6- ⁇ [4- (trifluoromethoxy)benzyl]oxy ⁇ -6,7-dihydro-5H-imidazo[2, l-b] [ 1 ,3]oxazine (pretomanid; PA824), pyrazinamide, rifampin, rifampicin, rifabutin, streptomycin, and combinations thereof.
  • the anti-tuberculosis drug is a combination of isoniazid (INH) and rifampin.
  • the anti-tuberculosis drug is isoniazid (INH).
  • the anti-tuberculosis drug is a combination of isoniazid, rifampin and fluoroquinolone.
  • the anti-tuberculosis drug is a combination of isoniazid, rifampin, fluoroquinolone and at least one of amikacin, kanamycin, and/or capreomycin.
  • the dose of the further drug or treatment used in combination with the compounds claimed herein depends on the nature of the treatment to be given.
  • the dose of a further drug that is administered to the subject or patient is to be in an effective amount, that is an amount effective to achieve the desired results, which is the treatment, prevention or inhibition of the disease in question.
  • the actual dose of a further drug or therapy may vary depending on, for example, the weight, metabolism, underlying medical conditions, contraindications, the length of treatment, the severity of the disease to be treated and the like.
  • the further drug is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg, between about 1 mg/kg to about 5 mg/kg, between about 2.5 mg/kg to about 8 mg/kg, between about 6 mg/kg to about 12 mg/kg, between about 8 mg/kg to about 14 mg/kg; between about 7 mg/kg to about 11 mg/kg; between about 9.5 mg/kg to about 12 mg/kg and between about 10.5 mg/kg to about 15 mg/kg of the body weight of the patient.
  • the further drug is an antituberculosis drug, which is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg, between about 1 mg/kg to about 5 mg/kg, between about 2.5 mg/kg to about 8 mg/kg, between about 6 mg/kg to about 12 mg/kg, between about 8 mg/kg to about 14 mg/kg; between about 7 mg/kg to about 11 mg/kg; between about 9.5 mg/kg to about 12 mg/kg and between about 10.5 mg/kg to about 15 mg/kg of the body weight of the patient.
  • the anti-tuberculosis drug is administered at a concentration ranging from 5mg/kg to 20 mg/kg.
  • the concentration administered to the patient may also vary, depending on whether the infection to be treated is a latent or active infection.
  • the dose administered to the patient is 5 mg/kg for a patient deemed to have an active tuberculosis infection.
  • the dose administered to the patient is between 10 mg/kg to 20 mg/kg for a patient deemed to have a latent tuberculosis infection.
  • the compounds disclosed herein can be administered to provide systemic distribution of the compound within the patient.
  • the compound(s) disclosed herein are administered to produce a systemic effect in the body.
  • the compounds disclosed herein are administered directly to the site affected by the condition, as, for example to the lung or the infected areas, using the requisite means, which will be apparent to a person skilled in the art.
  • the compounds disclosed herein are administered systemically, via oral, mucosal (including sublingual, buccal, rectal, nasal, or vaginal), parenteral (including subcutaneous, intramuscular, bolus injection, intra-arterial, or intravenous), transdermal, or topical administration.
  • the compounds are administered intravenously.
  • the compounds disclosed herein are administered via oral administration.
  • the compounds disclosed herein are not administered via oral administration.
  • the compounds disclosed herein are to be administered to the patient in an effective amount.
  • the dosage to be administered to a patient would depend on, and be influenced by, different variables, for example, the weight, metabolism, underlying medical conditions, contraindications, the length of treatment, the severity of the disease to be treated and the like.
  • the compound is administered at a concentration ranging from between about 1 mg/kg to 2000 mg/kg (2 g/kg), between about 5 mg/kg to about 25 mg/kg, between about 10 mg/kg to about 15 mg/kg, between about 1.6 mg/kg to 35 mg/kg, between about 25 mg/kg to about 60 mg/kg, between about 50 mg/kg to about 150 mg/kg, between about 100 mg/kg to about 300 mg/kg, 100 mg/kg to about 2000 mg/kg (2 g/kg), between about 200 mg/kg to about 500 mg/kg, between about 250 mg/kg to about 800 mg/kg; between about 400 mg/kg to about 1000 mg/kg (1 g/kg); between about 600 mg/kg to about 1200 mg/kg (1.2 g/kg) and between about 700 mg/kg to about 1500 mg/kg (1.5 g/kg) of the body weight of the patient.
  • the compound is administered at a concentration of 10 mg/kg, or 50 mg/kg, or 100 mg/kg, or 500 mg/kg, or 25 mg/kg.
  • dosage concentrations determined using animal models for example murine, porcine, or non-human primates may not exactly translate to the same dosage in humans, due to the obvious differences in anatomy and metabolism.
  • a dose of 100 mg/kg used in a murine model may result in a dose of roughly 500 mg/day for a 60 kg human.
  • a person skilled in the art is capable of extrapolating the required dose, for example for a human subject from, for example, data gathered from a mouse model.
  • composition, shape, and type of dosage forms of the invention will typically vary depending on their use.
  • a dosage form used in the acute treatment of a disease or a related disease may contain larger amounts of one or more of the active ingredients it comprises than a dosage form used in the chronic treatment of the same disease.
  • a parenteral dosage form may contain smaller amounts of one or more of the active ingredients it comprises than an oral dosage form used to treat the same disease or disorder.
  • the compounds disclosed herein are to be administered to a patient suffering from, or suspected to suffer from, a mycobacterial infection.
  • An infection is generally understood to be the infiltration and proliferation of a foreign organism, in most cases a pathogenic or an infectious organism, into and within a host, or a patient, as the case may be.
  • Infections can be caused by infectious agents including, but not limited to, viruses, viroids, prions, bacteria, nematodes (for example, parasitic roundworms and pinworms), arthropods (for example, ticks, mites, fleas, and lice), fungi (for example ringworm), and other macro-parasites such as tapeworms and other helminths.
  • the host is infected with bacteria.
  • the bacterium is mycobacterium. Infections can either subclinical (also known as a latent, silent, occult or inapparent infection) or clinical (also known as an active or apparent infection), depending on the absence or presence of symptoms other than the presence of the infectious agent. Therefore, a host is considered to have a latent infection when the presence of the infectious agent in the host is known but the host does not present any further symptoms. Examples of a latent bacterial infection are, but are not limited to, latent tuberculosis and latent viral infections, for example by viruses of the Herpesviridae family. In one example, the patient has a latent infection. In another example, the patient has an active infection.
  • the patient has a latent tuberculosis infection.
  • the patient has an active tuberculosis infection.
  • acute in conjunction with infection is generally used to denote a short-term infection, whereas the term “chronic” is used to denote a long-term infection.
  • chronic is used to denote a long-term infection.
  • infection is often used to denote any presence of a particular pathogen at all (no matter how little the amount), but is also often used to imply a clinically apparent infection, that is a case of infectious disease.
  • the term “infection” can also be replaced by the term “colonization” when referring to the situation of a latent infection, that is the situation where pathogens are present but no clinically apparent infection (no disease) is present.
  • Also disclosed herein is the use of a compound which enhances activity of an NAD + -dependent deacetylase in the manufacture of a medicament for preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof.
  • a compound for use in preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof wherein the compound enhances activity of an NAD + -dependent deacetylase.
  • a sirtuin enhancer for use in preventing, treating or preventing intracellular mycobacterial infections.
  • beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of extent of condition, disorder or disease; stabilized (i.e. not worsening) state of condition, disorder or disease; delay or slowing of condition, disorder or disease progression; amelioration of the condition, disorder or disease state, remission (whether partial or total), whether detectable or undetectable; or enhancement or improvement of condition, disorder or disease.
  • Treatment includes eliciting a cellular response that is clinically significant, without excessive levels of side effects. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment.
  • Mycobacterium tuberculosis infection downregulates SIRT1 expression
  • SIRTl mRNA levels were lowest in active tuberculosis patients compared with healthy and latent tuberculosis individuals (Fig. 1G). Lower expression of SIRTl mRNA in active tuberculosis individuals was also observed in the SA' 13 cohort (Fig. 7D). Notably, SIRTl mRNA levels were also reduced in HIV patients with tuberculosis as comorbidity, compared to those with HIV alone (SA' 14 cohort; Fig. 1G).
  • SIRTl activation restricts intracellular Mycobacterium tuberculosis growth, and induces phagosome-lysosome fusion and autophagy
  • SIRTl activity can be enhanced by resveratrol (trans-3,5,4'-trihydroxystilbene; RES; a natural activator) and SRT1720 (N-[2-[3- (piperazin- l-ylmethyl)imidazo[2, 1 -b] [ 1 ,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide; SRT; a synthetic activator).
  • enhancing SIRTl activity by resveratrol and SRT1720 using concentrations that are not toxic for cells (Fig. 9, A and B), inhibited the growth of intracellular Mycobacterium Bacillus Calmette-Guerin (Fig. 9C) and Mycobacterium tuberculosis in THP-1 cells in a dose- and time-dependent manner (Fig. 2, B-D).
  • SRT1720 treatment also inhibited the growth of intracellular Mycobacterium Bacillus Calmette-Guerin in human monocyte-derived macrophages (hMDMs; Fig. 9D). This effect was abolished in cells where SIRT1 was genetically inactivated (Fig. 2E) or chemically inhibited (Fig. 9E).
  • resveratrol reversed the expression pattern of 3062 of these genes (Quadrant X and Y in Fig. 10B and Table 3).
  • SRT-mediated SIRTl activation induced autophagy as assessed by upregulation of the autophagy-associated marker protein MAP1LC3A (LC3; Fig. 2H and Fig. 11A) and generation of its lipidated form (Fig. 21).
  • SIRT1 activation normalize Mycobacterium tuberculosis -induced inflammatory responses by deacetylating RelA/p65
  • SIRT1 is a master regulator of chromatin remodelling and thus reprograms gene expression.
  • Gene Ontology (GO) analysis was performed on 3062 resveratrol modulated genes in Mycobacterium tuberculosis infected cells (Fig. 10A). This indicated enrichment of GO processes involved in the inflammatory response, DNA damage restoration, telomere maintenance, and viral defence responses (Fig. 3, A and B, and Table 4). A similar trend was observed when the 3062 genes were analysed using Ingenuity Pathway Analysis (IPA).
  • IPA Ingenuity Pathway Analysis
  • Pathways such as triggering receptors expressed by myeloid cells (TREM)-l signalling, liver-X-receptor (LXR) activation, activation of interferon regulatory factors (IRF) by pattern recognition receptors (PRR), interferon signalling, and notably, NF- ⁇ signalling, were associated with host cell genes upregulated by infection and downregulated by resveratrol (Fig. IOC and Table 5). This data suggests that resveratrol-mediated SIRT1 activation results in the normalization of genes and pathways that are modulated by Mycobacterium tuberculosis.
  • TAM myeloid cells
  • LXR liver-X-receptor
  • IRF interferon regulatory factors
  • PRR pattern recognition receptors
  • NF- ⁇ signalling notably, NF- ⁇ signalling
  • SIRT1 activation reduces Mycobacterium tuberculosis growth in mice
  • SIRT1 -deficient mice myeloid cell-specific SIRT1 knockout; Mac-SIRTl KO
  • resveratrol and SRT1720 were infected with Mycobacterium tuberculosis and were found to display higher bacillary loads compared with wild-type controls (Fig. 4A).
  • resveratrol and SRT1720 inhibited the growth of Mycobacterium tuberculosis in the lungs and spleens of infected mice (Fig.
  • mice treated with isoniazid in combination with SRT1720 showed decreased bacillary loads in the lungs compared with mice receiving isoniazid alone (Table 1).
  • SIRTl activators reduce Mycobacterium tuberculosis mediated tissue pathology and inflammation in mice
  • SIRTl activation modulates the lung myeloid landscape in Mycobacterium tuberculosis infected mice
  • These differentiated clusters included diverse phenotypes, i.e., Ly6C + (Cluster 23, 24, and 25) and Ly6C l0 (Cluster 9, 18, and 19) monocytes; CDl lb + dendritic cells (Cluster 7); plasmacytoid DCs (Cluster 11); CD64 + MerTK + Siglec-F " interstitial macrophages (Clusters 13, 15, and 20); Ly6G + neutrophils (Clusters 4 and 10); eosinophil's (Cluster 1); and innate lymphoid like cells (ILCs; Clusters 21 and 34) (Fig. 6, A and B and Fig. 14). The differential abundance of these cell subsets was confirmed using manual gating (Fig. 6C and Fig. 17, B and C). SRT1720 treatment had minimal effect on uninfected animals as indicated by mixed clustering of cells from uninfected animals, with or without SRT1720 treatment (Fig. 6B).
  • Phenotyping of these six clusters identified them as Ly6C lo CDl lb lo F4/80 + monocytes (Cluster 18 and 19); Ly6C + CDl lb lo F4/80 + monocytes (Cluster 23); Ly6G + CDl lb l0 neutrophils (Cluster 10); CD25 + CDl lb + Sca-l + innate lymphoid cells (Cluster 21); and Siglec-F + eosinophil's (Cluster 1) (Fig. 6D and fig. S I ID).
  • Mycobacterium tuberculosis infected Mac-SIRTl KO mice displayed an increased percentage and numbers of CD1 lb lo F4/80 + (Ly6C l0 or Ly6C + ) monocytes in the lung compared with wild-type mice as early as 3 days post-infection (Fig. 17E and Fig. 6H, respectively).
  • a reduced frequency of CD45 + CDl lc + cells (Fig. 17F) was noted in the lungs of SRT1720-treated Mycobacterium tuberculosis -infected mice compared with untreated mice, which was also apparent in the CyTOF experiments (i.e. CD45 + CDl lc + dendritic cells, Fig.
  • SIRT1 have been described to play a role in the regulation of autophagy and can also directly affect AMPK activity, which has been shown to be clinically beneficial.
  • AMPK AMPK activity
  • the capacity of both SIRT1 and AMPK to modulate innate immune mechanism and inflammation emphasizes the importance of the SIRT1-AMPK axis in, (i) rewiring the host anti-microbial arsenal, and (ii) skewing the immuno-pathological balance towards protective immunity against Mycobacterium tuberculosis, leading to enhanced host benefits.
  • Tuberculosis pathogenesis is associated with early infiltration of myeloid cells into infected tissues. Inconsistencies in the naming and working definitions of myeloid cell subsets have complicated the objective description and quantification of cellular innate immune responses. Moreover, inflammatory conditions can dramatically change expression of many defining markers in activated cells. Utilizing a previously described unbiased high- dimensional analysis, the myeloid compartment in the lungs of Mycobacterium tuberculosis infected mice and found that SIRTl activation modulated the infiltration of a particular subset of Ly6C l0 /Ly6C + CDl lb lo F4/80 + monocytes.
  • Ly6C +/1 ° cells in SRT1720 treated Mycobacterium tuberculosis infected mice could also favour SRT1720 mediated Mycobacterium tuberculosis control.
  • the recruitment of Ly6C monocytes into the tissues occurs via engagement of the chemokine receptor CCR2 with MCP-1 (CCL2), a chemokine regulated by SIRTl.
  • ILC-like cells and eosinophils in the lungs of Mycobacterium tuberculosis infected mice upon SIRTl activation, cell subsets that were downregulated by Mycobacterium tuberculosis.
  • ILCs Innate lymphoid cells
  • the data provides new insights into the plasticity/ heterogeneity of lymphoid cells during Mycobacterium tuberculosis mediated chronic inflammation and indicates the role of SIRTl activators in controlling Mycobacterium tuberculosis growth/pathogenesis by regulating myeloid cell infiltration in the lungs of Mycobacterium tuberculosis infected mice.
  • SIRTl activators have a favourable safety profile. Therefore, their usage as an host-directed therapies for tuberculosis could have important clinical implications through (i) avoiding the development of resistance by targeting the host and not the pathogen; (ii) shortening the course of multi-drug therapy for tuberculosis; and (iii) improving anti- Mycobacterium tuberculosis immune responses to facilitate pathogen clearance. Also as SIRTl activators modulate monocyte/macrophage subsets and chronic inflammation, they could prevent long-term pulmonary morbidity due to lung destruction in tuberculosis patients. Overall, the data provided herein demonstrates an important role for SIRTl in the Mycobacterium tuberculosis infection-associated immunopathogenesis, and suggests that activation of SIRTl can improve tuberculosis treatment outcome. Materials and Methods
  • Study Design The objective of this study was to study the effect of Mycobacterium tuberculosis infection on host energy sensor viz. Sirtuins, regulating range of immuno-metabolic processes, and whether the functional connection between immune response and metabolism could be harnessed to control tuberculosis.
  • SIRTl Sirtuin 1
  • anti SIRTl (#07-131; Millipore), anti-NF- ⁇ p65 (C-20 #SC-372; Santa Cruz Biotechnology Inc), anti-NF- ⁇ p65 (acetyl K310) antibody (#abl9870; AbCam), anti-LC3B (#3868; Cell Signaling Technologies), anti-GAPDH (14C10) (#2118; Cell Signaling Technologies), anti-rabbit IgG, HRP-linked antibody (#7074; Cell Signaling Technologies) and mouse anti-rabbit IgG (Conformation Specific) mAb (L27A9) (#3678; Cell Signaling Technologies).
  • Stealth SIRTl siRNAs (Set of 3: HSS 118729, HSS 177403, HSS 177404) and control siRNAs were from Life Technologies and Integrated DNA technologies respectively (#1299001).
  • THP-1 Cell culture Human monocyte THP-1 cells from ATTC were maintained in Roswell Park Memorial Institute (RPMI-1640) medium (Gibco), supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1% sodium pyruvate, 1% L-glutamine, 1% nonessential amino acids (Life technologies), and 1% kanamycin (Sigma- Aldrich), at 37°C in a 5% CO 2 humidified atmosphere. In infection experiments, no antibiotic was used.
  • RPMI-1640 Roswell Park Memorial Institute
  • FBS heat-inactivated fetal bovine serum
  • FBS heat-inactivated fetal bovine serum
  • sodium pyruvate 1% sodium pyruvate
  • L-glutamine 1% L-glutamine
  • nonessential amino acids Life technologies
  • kanamycin Sigma- Aldrich
  • hMDMs human monocyte-derived macrophages
  • PBMCs Peripheral blood mononuclear cells
  • Monocytes were enriched from PBMCs by CD 14 magnetic selection (Miltenyi-Biotec beads).
  • the purified CD14 + monocytes were re-suspended in RPMI 1640 with 10% FBS, 1% penicillin, 2 mM L-glutamine, and 100 ng/ml human macrophage colony- stimulating factor (M-CSF, R&D Systems), and incubated in six-well plates at 37°C in 5% C0 2 for six days. The medium was changed on the fourth day.
  • M-CSF human macrophage colony- stimulating factor
  • Mtb Mycobacterium tuberculosis
  • HN878, CDC1551, Erdman, W148, AH30, CC13, AI10, KY strains and Mycobacterium bovis bacillus Calmette-Guerin (BCG) were grown in Middlebrook 7H9 broth (BBL Microbiology Systems), supplemented with albumin dextrose-catalase (ADC, Difco laboratories) and 0.05% Tween 80 at 37°
  • mycobacterial cells were pelleted, re-suspended in fresh 7H9 broth with 20% glycerol, and stored at -80°C.
  • One vial of the stock was thawed to enumerate CFU/ml.
  • the cells were thawed, washed, and sonicated prior to use.
  • Drug-resistant strains were maintained at the Public Health Research Institute (PHRI), Newark, USA.
  • the infected cells were counted, seeded in triplicate, and either left untreated or treated with different compounds for the indicated time periods.
  • mycobacteria-infected cells were pre-treated with SIRT1 inhibitor EX527 for 0.5 hours before addition of SIRT1 activators.
  • SIRT1 inhibitor EX527 for 0.5 hours before addition of SIRT1 activators.
  • THP-1 cells were differentiated for 16-18 hours using 4 ⁇ phorbol myristate acetate (PMA, Sigma) prior to infection with multi-drug resistant (MDR) strains of Mycobacterium tuberculosis.
  • PMA phorbol myristate acetate
  • PrestoBlueTM Cell Viability Reagent (Invitrogen) was used to assess the cell viability of THP-1 cells upon addition of resveratrol or SRT1720 at varying concentrations over 72 hours. 20 ⁇ ⁇ was added to each well and incubated for 20 minutes at 37 °C, and fluorescence was read on a plate reader excited at 560 nm with non-conjugated light emissions collected at 590 nm.
  • NAD + to NADH ratio measurement Quantification of NAD + and NADH was carried out using the NAD + /NADH assay kit (Abeam #ab65348), according to the manufacturer's instructions. NAD + and NADH values were normalized by protein concentration.
  • Membranes were developed using the indicated primary antibody at a 1: 1000 dilution, and secondary antibodies at a 1:3000 dilution in blocking solution. This was followed by incubation in chemiluminescent horseradish peroxidase (HRP) detection reagent (Millipore) for 1 minute prior to image acquisition.
  • HRP horseradish peroxidase
  • ChIP Chromatin immunoprecipation assay. ChIP assays were performed with samples from uninfected and Mycobacterium tuberculosis infected THP-1 cells, treated or untreated with SRT1720, using the anti- Fi B p65 antibody (C-20, Santa Cruz Biotechnology Inc) or normal rabbit IgG, with the SimpleChIP Plus Enzymatic Chromatin IP Kit (Cell Signaling Technologies), following the standard protocol. DNA fragments were subjected to qRT-PCR using primers flanking NF- ⁇ response elements on various targets. ChIP qRT-PCR data analysis was performed.
  • THP-1 cells were infected with GFP-conjugated BCG. After infection, cells were incubated with 500 nM LysoTracker (LTR; Invitrogen) in the presence or absence of drugs for 4 or 24 hours. Cells were then washed with PBS and fixed in 4 % paraformaldehyde for 20 minutes at room temperature. Fixed cells were then washed with phosphate-buffered saline (PBS). Fluorescence intensities of GFP- BCG and LTR were analysed using an Olympus FV1000 confocal microscope and used to calculate the number of bacteria co-localized with LTR together with the total number of intracellular bacteria. In total, at least 200 infected cells were counted for different analyses.
  • LTR nM LysoTracker
  • mice Female C57BL/6 mice (6-8 weeks old) were infected with Mycobacterium tuberculosis H37Rv using the nose-only aerosolization system (CH Technologies). Three to four animals were sacrificed on day 1 to determine the number of bacteria implanted in the lungs. Seven days after infection, animals were randomly distributed into different groups prior to the start of treatment in the acute model. In the chronic model, treatment was started at day 40 post-infection. Treatment with the indicated drugs was administered by gavage once a day, six days a week.
  • CH Technologies nose-only aerosolization system
  • mice were sacrificed at predetermined time points (two or four weeks after initiation of treatment), followed by harvesting of tissues and enumeration of Mycobacterium tuberculosis colony forming units (CFU).
  • CFU Mycobacterium tuberculosis colony forming units
  • the myeloid cell-specific SIRTl KO (Mac-SIRTl KO) mice were a gift from Xiaoling Li (National Institute of Environmental Health Sciences).
  • mice expressing a conditional SIRT1 floxed allele bred into a C57/BL6 background were crossed with mice expressing Cre recombinase under a myeloid- specific cell promoter.
  • Mac-SIRTl KO mice were housed in a biosafety level 3 (BSL3) laboratory at the University of Massachusetts Medical School (UMMS), USA, and treated humanely using procedures described in animal care protocols.
  • CyTOF marker labelling was performed to validate CyTOF data (in independent experiment) and to assess the infiltration of myeloid cells in Mycobacterium tuberculosis infected Mac-SIRTl KO mice.
  • Morphometry of the lesions was performed also using SigmaScan Pro 5. A calibration micrometre slide was used to determine the area evaluated. The system allows performing the analysis at significantly higher magnification and resolution on digital images. The area of all lesions in a section was measured first and then the percentage from the area of the whole section was calculated (lung involvement).
  • Raw expression data was extracted using GenomeStudio Gene Expression v 1.9.0, and processed with quantile normalization. Hierarchical clustering analysis with complete linkage algorithms was performed using R. Heat maps were plotted using SpotFire (TIBCO Software Inc. http://spotfire.tibco.com ). Differential expression analysis was performed using Linear Models for Microarray Data (LIMMA). GO analysis was carried out by DAVID. Pathway analysis was carried out using IPA (Ingenuity® Systems, www.ingenuity.com).
  • control lung samples were labelled with Cy3 while lesion samples were labelled with Cy5 and co-hybridized on arrays.
  • CFU chronic tuberculosis model bacterial load
  • mice were co-administered with INH and 100 mg/kg of SRT.
  • Table 3 Differentially expressed genes between Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol (RES) vs untreated cells. Corresponding log fold changes of Infected vs Uninfected cells are also shown.
  • RES resveratrol
  • ILMN_ .1654690 27440 CECR5 0.356 1.27E-04 -0.501 1.30E-06
  • ILMN_ .1655935 113 ADCY7 0.704 1.25E-09 -0.416 1.67E-05
  • ILMN_ .1658483 3552 ILIA 1.114 1.97E-13 -0.404 4.09E-05
  • ILMN_ .1662799 63940 GPSM3 0.251 1.54E-03 -0.344 3.51E-05
  • ILMN_ .1670305 710 SERPWG1 2.806 1.13E-22 -1.798 2.53E-18
  • ILMN_ 1694140 134265 AFAP1L1 0.264 9.43E-03 -0.287 3.22E-03
  • ILMN_ .1701195 7941 PLA2G7 2.581 4.76E-24 -1.401 1.62E-17
  • ILMN_ . 1702237 2280 FKBP1A 0.309 2.43E-04 -0.277 6.93E-04
  • ILMN_ .1707088 79961 DENND2D 0.615 1.92E-07 -0.389 5.63E-05
  • ILMN_ . 1707292 339210 C17orf67 1.013 2.41E-13 -0.295 8.11E-04
  • ILMN_ .1707591 79931 TNIP3 1.250 1.95E-15 -0.605 1.45E-08
  • ILMN_ .1707975 3053 SERPIND1 0.368 1.51E-03 -0.469 3.07E-05
  • ILMN_ .1710906 153830 RNF145 0.576 1.07E-06 -0.263 5.35E-03
  • ILMN_ .1733176 3987 LIMS1 0.847 7.47E-12 -0.863 5.59E-12 ILMN_ .1733249 59345 GNB4 0.583 1.99E-05 -0.475 4.32E-05
  • ILMN_ .1739751 284129 SLC26A11 1.847 5.27E-18 -0.773 3.06E-09 ILMN_ . 1739967 29110 TBK1 0.775 1.08E-11 -0.318 1.44E-04
  • ILMN_ .1750805 257106 ARHGAP30 0.809 1.35E-11 -0.378 2.40E-05
  • ILMN_ .1752281 23317 DNAJC13 0.249 3.17E-03 -0.241 4.81E-03
  • ILMN_ .1756860 9352 TXNL1 0.302 3.20E-03 -0.279 5.65E-03
  • ILMN_ . 1760027 7454 WAS 0.304 4.19E-04 -0.488 3.56E-07
  • ILMN_ .1762260 718 C3 1.270 4.04E-15 -0.521 1.77E-07

Abstract

Disclosed is a method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereo comprising administering a compound which activates activity of an NAD+-dependent deacetylase such as sirtuins 1, 2, 3, 4, 5, 6 and 7. In one preferred embodiment, the agent activates NAD-dependent deacetylase SIRT1, and may be SRT1720. Also disclosed is the use of sirtuin enhancers in combination with other anti-tuberculosis drugs for treatment of mycobacterial infection, in particular, the use of SRT1720 and isoniazid (INH).

Description

INHIBITION OF INTRACELLULAR GROWTH OF MYCOBACTERIUM SPECIES
AND ITS APPLICATIONS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of Singapore provisional application No. 10201600326T, filed on 15 January 2016, the contents of it being hereby incorporated by reference in its entirety for all purposes.
FIELD OF THE INVENTION
[0002] The present invention generally relates to the field of microbiology and immunology. In particular, the present invention relates to compounds that specifically target and modulate host immune response to control and treat bacterial infections.
BACKGROUND OF THE INVENTION
[0003] Antibiotics or antibacterial agents are agents that are used to inhibit the growth or kill bacteria. As commonly known, bacteria can develop resistance to antibiotics or antibacterial agents. Resistance of a bacterium to an antibiotic can range from substantially greater tolerance or reduced susceptibility to completely unaffected by the antibiotics. When a bacterium cannot be controlled or killed by antibiotics or antibacterial agents, the bacteria is able to survive, multiply and cause disease or damages to the hosts despite being in the presence of the antibiotic when such scenario occurs, the bacteria is considered resistant to drug (i.e. drug resistant bacteria). Due to the increased reliance on antibiotics to treat common diseases, antibiotic resistant bacteria are rapidly on the rise. Such antibiotic resistant bacteria have become a significant public health threat. This is the case in Tuberculosis (TB), caused by Mycobacterium tuberculosis, also. Tuberculosis (TB) pathogenesis is driven by a complex interplay between the host immune system and the survival strategies of the bacterium. The ability of, for example, Mycobacterium tuberculosis to persist in protected niches within the body delays the efficacy of current antibiotic therapy, contributing to the emergence of, for example, multi-drug resistant (MDR) strains. An effective host immune response is important for the containment of persistent bacterial infections, for example a Mycobacterium tuberculosis infection, and this immune response is closely linked to the metabolic programs of the host. The capability of, for example, Mycobacterium tuberculosis to execute a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limits the efficacy of current antibiotic mediated therapy and leads to the emergence of drug- resistant strains. Therefore, there is an urgent need to develop new therapeutic strategies, such as host-directed therapies (HDTs) that enhance host immunity against bacterial infections.
SUMMARY
[0004] In one aspect, the present invention refers to a method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the method comprises administration of a compound which enhances activity of an NAD+- dependent deacetylase.
[0005] In another aspect, the present invention refers to use of a compound which enhances activity of an NAD+-dependent deacetylase in the manufacture of a medicament for preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] The invention will be better understood with reference to the detailed description when considered in conjunction with the non-limiting examples and the accompanying drawings, in which:
[0007] Fig. 1 shows data showing that the presence of Mycobacterium tuberculosis infection downregulates SIRTl expression. (A) shows column graphs of the results of SIRTl mRNA that was assessed by qRT-PCR in Mycobacterium tuberculosis infected THP-1 cells over 72 h. SIRTl expression normalized to GAPDH expression, relative to uninfected cells (UN), is shown. (B) shows images of a Western blot analysis of SIRTl and GAPDH (control) of Mycobacterium tuberculosis infected THP-1 cells, under the conditions as recited in A. (C) shows further column graphs depicting the results of SIRTl mRNA expression, which was assessed in the lungs of Mycobacterium tuberculosis infected mice at different time points post-infection. UN - uninfected mice (n = 4); d = days post infection. (D) shows box plots depicting the SIRTl mRNA expression in the lungs of Mycobacterium tuberculosis-infected macaques with either active or latent tuberculosis disease. Fold change of SIRTl expression in lesions versus normal lung tissue is shown (n = 10 - 12). (E) shows micrograph images of immunostained lung tissue sections of a representative macaque from uninfected; BCG- vaccinated- and unvaccinated Mycobacterium tuberculosis infected group; showing reduced SIRT1 (arrow) in unvaccinated Mycobacterium tuberculosis infected macaques. Nuclear staining - dots in grey. NC - necrotic core of granuloma. Magnification 20x. (F) shows histograms representing the percentage of pulmonary cells expressing SIRT1 from images shown in (E) (n = 8 - 20). Data in (A)-(C) are representative of 3-4 independent experiments. Values are expressed as mean + SEM. * P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 determined using two-tailed Student's t-test (A, C) and Mann -Whitney test (D, F). (G) shows scatter plots illustrating the raw intensity values for SIRT1 mRNA expression in the data sets of different tuberculosis cohorts, i.e., UK 2010, South Africa 2010, and South Africa 2013. Bar indicates the median. *P < 0.05, ****P < 0.001 determined using Mann- Whitney test. (H) shows SIRT1 mRNA expression data, also depicted as a scatter plot, from active tuberculosis patients undergoing standard chemotherapy treatment from a China 2014 cohort. Red bar indicates the median, *P < 0.05, **P < 0.01, ****P < 0.001 by Mann-Whitney and paired Wilcoxon signed-rank test.
[0008] Fig. 2 shows data illustrating that SIRT1 activators enhance control of Mycobacterium tuberculosis growth. (A) shows a bar chart comparing Mycobacterium tuberculosis growth after 24 hours in scrambled control (WT) and SIRT1 knock down (SIRTl~ ~) THP-1 cells, presented as a fold change compared to uninfected cells. Average of three independent experiments is shown. (B) shows line graphs depicting a difference in Mycobacterium tuberculosis growth after treatment of THP-1 cells with a vehicle control or 100 μΜ of resveratrol (RES). (C) shows a line graph depicting the change in Mycobacterium tuberculosis growth after 24 hours in THP-1 cells treated with different doses of SRT 1720 (SRT). (D) shows line graphs illustrating the difference in Mycobacterium tuberculosis growth after treatment of THP-1 cells with vehicle control or 5 μΜ of SRT. (E) shows a bar chart depicting the differences in Mycobacterium tuberculosis growth after 24 hours in scrambled control (WT) and SIRTl"7" THP-1 cells treated with either a vehicle control, 5 μΜ of SRT1720 or 100 μΜ of resveratrol. Data is presented as fold change relative to control. (F) shows multiple line graphs, each showing the growth of different multi-drug resistant (MDR) strains of Mycobacterium tuberculosis (e.g. HN878; W148; CC13; AI10; AH30 and KY) after 72 hours in THP-1 cells treated with either a vehicle control, 100 μΜ isoniazid (INH), 5 μΜ SRT1720 or 100 μΜ RES. The name of each strain is indicated on the respective graph. Growth restriction by SRT 1720 and resveratrol are shown to be significant over the control, as calculated by ANOVA. (G) shows a scatter plot of genes involved in autophagy that are differentially expressed in Mycobacterium tuberculosis infected THP-1 cells [I] vs uninfected cells [U], and in Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol [R] vs untreated [I]. Positive and negative regulators of autophagy shown to be enriched are found in the upper left and lower right quadrants of the scatter plot, respectively, lfc - log fold change. (H) shows flow cytometry histograms of wild type (WT), scrambled control (NC) or SIRTl"7" THP-1 cells which were infected with Mycobacterium tuberculosis for 3 hours and incubated with or without 5 μΜ of SRT1720, 100 μΜ of resveratrol or 200 nM Rapamycin (positive control) for 4 hours, immunolabelled with anti-LC3B and Alexa 647- conjugated goat anti rabbit IgG, and analysed by flow cytometry. Shown is a representative histogram of four independent experiments. These histograms show the intracellular expression level of LC3 in the cells. An increase of LC3 indicates an increase of autophagy in the cell population, thereby showing the efficacy of the applied compound in cell killing. (I) shows an image of an immunoblot of WT, NC or SIRTl"7" THP-1 cells which were infected and treated with 5 μΜ of SRT1720 for 24 hours. The cell lysates were then subjected to immunoblot analysis for LC3 and for GAPDH. LC3 II/LC3 I ratio is indicated. This indicates that SRT1720 treatment induces autophagy in WT and NC cells, and not in SIRTl"7" cells, according to the band shown for LC3 II. (J) shows fluorescent images of THP-1 cells, which were infected with BCG-GFP for 3 hours and incubated with one of the following: with or without 5 μΜ SRT1720, 1 μΜ EX527 (EX; a sirtuin inhibitor) or EX + SRT1720. All samples were then incubated with 500 nM LysoTracker (LTR, a fluorescent dye for labelling and tracking acidic organelles in live cells) for 4 hours before fixation. Scale bar represents 5 μιη. This data shows co-localization bacteria (BCG-GCP) with acidic vacuoles and thus indicates that SRT1720 treatment enhances the phagosome-lysosome fusion and that this enhancement of phagosome-lysosome fusion is SIRTl specific. (K) shows a bar chart representing the quantification of LTR-positive BCG-GFP in THP-1 cells, under the same conditions as illustrated in (J). Data in (B) to (E) and (H) to (K) are representative of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 as determined using two-tailed Student's t-test.
[0009] Fig. 3 shows data showing that SIRTl activators normalize Mycobacterium tuberculosis induced inflammatory responses. (A) shows a Circos figure depicting gene ontology (GO) pathways modulated by resveratrol (RES) treatment (24 hours) during Mycobacterium tuberculosis infection. The inner circular bar represents the number of genes in each GO category. The middle circular bar represents the number of genes in particular GO category that were significantly changed upon infection (I (infected) vs. U (uninfected)). The outer circular bar shows the number of genes significantly modulated by resveratrol treatment of the infected cells (R (RES -treated, infected) v I (infected)). A cut-off of lxlO"4 was used for the GO pathways. Black lines indicate pathways sharing at least 50% of genes. The thickness of the line shows the extent of overlaps between the two pathways. (B) shows a heat map depicting the comparison of 149 genes from Inflammatory response section (GO:0006954) shown in (A), present within 3062 genes that are modulated by resveratrol (See Fig. 10 A). This heat map displays absolute expression values of the upregulated and downregulated genes in the respective analysis. (C) shows line graphs depicting the change in mRNA expression levels of IL6, TNFa, MCP-1, and ILIB (cytokines which are indicative of a presence of an immune response in a subject) in Mycobacterium tuberculosis infected THP-1 cells, untreated (IN - infected) or treated with 5 μΜ of SRT1720 over a period of 72 hours. (D) shows a bar chart, which shows the estimation of the concentration of the cytokines ΙΣΙβ, IL6, and MCP-1, respectively, in the culture supernatant of Mycobacterium tuberculosis infected THP-1 cells at 24 hours post-infection, which had been treated with 5 μΜ SRT1720 or control (DMSO), as measured by ELISA. (E) shows a line graph depicting decrease in mRNA expression of RelA/p65 upon SRT1720 treatment under the conditions as stated in in (C). (F) shows images of immunoblots of cell lysates from uninfected (UN), LPS (Lipopolysaccharide) (lOO ng/ml) stimulated, and Mycobacterium tuberculosis infected THP-1 cells, either untreated or treated with 5 μΜ SRT1720 over a period of 72 hours. (G) shows a column graph showing the relative protein band density of RelA/p65 and acetylated RelA/p65, normalized to GAPDH at 72 hours. Acetylated p65 enhances an immune response, so the deacetylation of RelA/p65 will prevent an immune response from occurring. Thus, it is shown here that SRT1720 treatment reduces the amount of total p65 and deacetylated p65, thereby modulating an immune response. (H) shows column graphs depicting the effect of SRT1720 treatment on RelA/p65 recruitment to TNFa, ILIB, IL6, and MCP-1 promoters in Mycobacterium tuberculosis infected THP-1 cells. Chromatin immunoprecipitation (ChIP) assays were performed with an antibody against RelA/p65 or control rabbit IgG. Aliquots of chromatin were obtained before (Input) or after IP. Isolated chromatin was quantified by realtime PCR. Data is expressed as the fold change over the levels detected in the uninfected cells after correcting for differences in the amount of starting (input) chromatin material. Representative data from three (C) - (E) and two (F) - (H) independent experiments are shown. Data is expressed as mean + SEM performed in triplicate. *P < 0.05, **P < 0.01 is determined using a two tailed Student's t-test.
[0010] Fig. 4 shows data illustrating that SIRT1 activation reduces Mycobacterium tuberculosis growth in mice. (A) shows a scatter plot depicting the bacillary load in the lungs of control (WT) and Mac-SIRTl KO mice infected with Mycobacterium tuberculosis on day 21 post-infection. Bar indicates the median. (B) shows line graphs depicting the change in lung and spleen bacillary load of Mycobacterium tuberculosis infected mice treated with 50 or 100 mg/kg of resveratrol starting 7 days post-infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice. (C) shows line graphs depicting the change in lung and spleen bacillary load of Mycobacterium tuberculosis infected mice treated with 100 mg/kg of SRT1720 starting 7 days post- infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice. (D) shows a line graph depicting the change in lung bacillary load of Mycobacterium tuberculosis infected mice treated with 100 mg/kg of SRT1720 starting 40 days postinfection. Bacillary loads were enumerated on days 1, 7, 40, 55, and 68 post-infection. N=8- 12 mice per group per time point. Data is expressed as mean + SEM. A-D, combined data of two independent experiments is shown. *P < 0.05, **P < 0.01 by Mann-Whitney test.
[0011] Fig. 5 shows data showing that SIRT1 activation reduces tuberculosis associated tissue pathology and inflammation in mice. (A) shows light micrographs images of hematoxylin and eosin (H&E) staining of representative lung sections on day 35 postinfection from Mycobacterium tuberculosis infected mice, untreated or treated with 100 mg/kg resveratrol. Scale bar at 4x represents 500 micrometres (μιη), at 40x represents 50 micrometres (μιη). AFB - Acid fast bacilli. IN - Mycobacterium tuberculosis infected mice, IN+RES - resveratrol treated Mycobacterium tuberculosis infected mice. A higher number of acid fast bacilli appears to be present in the control untreated group. (B) is a scatter plot showing the percentage of lung area involved in disease pathology in the same groups of mice (IN (untreated) vs IN+RES (resveratrol treated Mycobacterium tuberculosis infected mice)). (C) is a scatter plot showing the percentage of lung area involved in disease pathology of Mycobacterium tuberculosis infected mice, either untreated or treated with 100 mg/kg SRT1720 (SRT) at day 35 post-infection. IN+SRT - SRT1720 treated Mycobacterium tuberculosis infected mice. (D) shows column graphs depicting changes in mRNA expression of the listed genes. Mycobacterium tuberculosis infected mice were treated with 100 mg/kg of SRT, starting 7 days post-infection. On day 35, RNA was extracted from the lungs and mRNA expression was assessed by qRT-PCR. (E) shows a column graph representing the absolute values of the listed inflammatory chemokines and cytokines from the lungs of Mycobacterium tuberculosis infected mice as in (D), as measured using Luminex. (F) shows a column graph comparing the change in gene expression between WT (Control) and Mac- SIRT1 KO mice infected with Mycobacterium tuberculosis. On day 14, RNA was extracted from the lungs and mRNA expression was assessed by qRT-PCR. (G) shows a column graph showing the estimated concentrations of ΙΣΙβ, TNFa and MCP-1 in the lung homogenate of mice in (F), as measured by ELISA. Bar lines in (B) and (C) represent the median. Subfigures (D) - (G) are representative of two independent experiments. Data is expressed as mean + SEM. *P < 0.05, **P < 0.01 by Mann-Whitney test.
[0012] Fig. 6 provides data showing that SIRT1 activation modulates the lung myeloid landscape in Mycobacterium tuberculosis infected mice. (A) shows a scatter plot showing the results of t-distributed stochastic neighbour embedding (tSNE) analysis, which was used to objectively delineate myeloid cell subsets of the lung. Aggregate tSNE dimensionality- reduced single-cell data from lung tissues of analysed mice were plotted and color-coded by the 28 'unsupervised' DensVM clusters. A grouped description of each cluster is indicated. Detailed characterizations of each cluster are described in Fig. 14. (B) shows a heat-plot summary of normalized cluster frequency (unsupervised clustering) across the different groups of mice, either untreated or treated with 100 mg/kg SRT 1720. UN - uninfected mice, UN+SRT - uninfected mice treated with SRT 1720, IN - Mycobacterium tuberculosis infected mice, IN+SRT - Mycobacterium tuberculosis infected mice treated with SRT 1720. "*" indicates clusters that were significantly altered in IN compared with UN. "+" indicates clusters that were significantly altered in IN+SRT compared with IN. (C) shows column graphs showing the frequency of CD45+CD3"CD90"CD19" (Ly6C subsets) in various cell populations as mass cytometry data, analysed by manual gating strategy (detailed in Fig. 15A). MQs - macrophages, DCs - dendritic cells and pDCs - plasmacytoid dendritic cells. (D) shows further t-distributed stochastic neighbour embedding (tSNE) analysis of cellular composition of lung tissues derived from UN (untreated), IN (infected) and IN+SRT (infected and treated with SRT1720) mice, highlighting six SRT1720 modulated clusters. Each plot represents a pool of 3 to 4 lung tissue cells. Clusters 1, 10, 18, 19, 21, and 23 are shown (circled). Ungrouped cells (remaining) are shown in gray. (E) shows column graphs depicting the mean frequencies of Ly6C subsets among CD45+ myeloid cells. Mass cytometry data was analysed by traditional gating strategy as in C. (F) shows scatter plots while (G) shows histograms depicting the results of fluorescent flow cytometric analysis performed to validate changes in Ly6Clo/Ly6C+ monocyte composition observed in the lungs of Mycobacterium tuberculosis infected animals upon SRT1720 treatment. (H) shows histograms showing the number of lung Ly6Clo/Ly6C+ CDl lbloF4/80+ monocytes in WT controls and Mac-SIRTl KO mice on day 3 post-infection. Data is expressed as mean + SEM. n = 4 - 6 mice per group per time point. *P < 0.05, **P < 0.01, #P <0.005 by Mann- Whitney test.
[0013] Fig. 7 shows data depicting the SIRT1 expression in Mycobacterium tuberculosis infected human cells and in the peripheral blood of humans infected with Mycobacterium tuberculosis and other diseases. (A) shows line graphs depicting the changes in RNA expression in THP-1 cells which were infected with Mycobacterium tuberculosis and cultured for 72 hours. RNA extracted from these cells was assessed by microarray. Expression data of SIRT1-SIRT7 mRNA in infected cells change relative to that in uninfected cells are depicted. (B) shows line graphs depicting the expression data of SIRT1 in Mycobacterium tuberculosis infected macrophages from the published dataset GSE51029. (C) shows a line graph representing the expression data of SIRT1 in Mycobacterium tuberculosis infected macrophages from Karim et al. (D) to (G) show the raw data of SIRT1 expression in the peripheral blood of different cohorts, which are Malawi/SA 2013 (D), UK 2010 (E), South Africa 2012 (F) and Viet 2008 (G). These cohorts are of active and latent tuberculosis patients and other diseases in which tuberculosis is a differential diagnosis. Less expression of SIRT1 mRNA were observed in active tuberculosis patients in these cohorts. Bar indicates median. *P< 0.05, **P< 0.01 as determined by Mann-Whitney and paired Wilcoxon signed-rank test.
[0014] Fig. 8 shows data showing that SIRT1 is expressed by CD68/CD163 macrophages in granulomas of Mycobacterium tuberculosis infected macaques. (A) shows representative confocal images of lung sections of an Mycobacterium tuberculosis infected BCG-vaccinated macaque showing the presence of SIRT1 in CD68/CD163 macrophages and the absence of SIRT1 in CD3+ T cells. Scale bar, 15 μΜ (Top) or 50 μΜ (Bottom). First column - CD68/CD163 or CD3, second column - SIRTl and third column - nuclei stain. Last column - merged figure of first three columns. (B) shows a bar graph illustrating the different in percentage expression of CD68/CD163 in SIRT1+ cells.
[0015] Fig. 9 shows data illustrating the downregulation of SIRTl expression by mycobacteria and control of mycobacterial growth by resveratrol and SRT 1720. (A) shows a line graph depicting the results of the evaluation of cell viability of THP- 1 cells which were treated with resveratrol (RES) at indicated concentrations for 72 hours. (B) shows a line graph showing the results of cell viability evaluation of THP-1 cells treated with SRT 1720 under the conditions as stated in A. (C) shows a line graph depicting the number of BCG in THP-1 cells which survived after 24 hour treatment with different doses of resveratrol (RES). (D) shows a column graph depicting the BCG survival in human monocyte-derived macrophages (hMDMs) upon treatment with vehicle control or 5 μΜ SRT 1720 (SRT) over a 48 hour period of infection. (E) shows line graphs showing BCG survival in THP-1 cells upon treatment with vehicle control or 100 μΜ RES in the absence or presence of 1 μΜ EX527 (EX; a sirtuin inhibitor), over a 48 hour infection period. The effect of resveratrol (RES) on mycobacterial growth was abolished in cells where SIRTl was chemically inhibited by 1 μΜ EX. (F) shows a line graph depicting BCG survival in THP-1 cells upon treatment with vehicle control, 5 μΜ SRT or 60 μΜ SA-3 over a 72 hour infection period. Growth of BCG in THP-1 cells is inhibited by treatment with 60 μΜ SA-3. (G) shows data illustrating that Mycobacterium tuberculosis infection led to a decrease in NAD+ levels in THP- 1 cells and thus decreases NAD+/NADH ratio, while SRT 1720 treatment elevates the NAD+/NADH ratio. (H) shows column graphs depicting the fold change of SIRTl mRNA expression, which was assessed by qRT-PCR in THP-1 cells infected with Mycobacterium tuberculosis, which were either untreated or treated with 5 μΜ SRT1720 over 72 hours. Relative expression normalized to GAPDH expression and to those of uninfected cells (UN) is shown. Data in (G) are expressed as mean NAD+/NADH ratio of two independent experiments performed in duplicate. All other experiments are carried out in triplicate and are representative of three independent experiments unless stated. *P< 0.05, as determined using two-tailed Student's t- test.
[0016] Fig. 10 shows data illustrating that resveratrol modulates the global gene expression during mycobacterial infection. (A) shows a flow chart depicting the strategy for analysis of microarray data. (DEGs - differentially expressed genes) (B) shows a scatter plot of genes differentially expressed in the Mycobacterium tuberculosis infected THP-1 cells versus uninfected cells (I vs U), and Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol (RES) versus untreated (R vs I). Expression of 3062 genes overlapped between the two treatments and reversed by RES treatment are shown in quadrant X and Y. (C) shows a table listing the results of Ingenuity's pathway analysis (IP A) of 3062 differentially expressed genes (DEGs), thereby indicating the modulation of the pathways by resveratrol (RES) treatment. In dark grey are genes downregulated by infection but upregulated by RES treatment (correspond to Quadrant Y in B), and in light grey are genes upregulated by infection and downregulated by RES (correspond to Quadrant X in B).
[0017] Fig. 11 shows data depicting that SIRT1 activation induces LC3 expression and phagosome-lysosome fusion in mycobacteria infected THP-1 cells. (A) shows flow cytometry histograms of wild type (WT) THP-1 cells which were infected with GFP conjugated BCG for 3 hours and incubated with either 5 μΜ of SRT or 100 μΜ Isoniazid (INH; Positive control) for 4 hours, or which remained untreated, and immunolabelled with anti-LC3B, followed by addition of Alexa 647 -conjugated goat anti rabbit IgG and analyzed by flow cytometry. Representative histogram of two independent experiments is shown. This figure shows that SRT treatment enhances LC3B expression in Mycobacterium BCG infected cells, whereby isoniazid (INH) is used as a positive control. (B) shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in THP-1 cells. WT THP-1 cells were infected as in (A) and treated with 5 μΜ SRT and 500 nM LysoTracker (LTR) for 4 hours before fixation. Quantification of LTR-positive Mycobacterium BCG-GFP is shown. (C) shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in THP-1 cells after 24 hours of treatment. WT THP-1 cells were infected as in (A) and treated with 5 μΜ SRT or 100 μΜ RES, and 500 nM LysoTracker (LTR) for 24 hours before fixation. Quantification of LTR- positive BCG-GFP is shown. (D) shows a column graph depicting the percentage of Mycobacterium BCG that co-localized with LysoTracker in SIRT1"7" THP-1 cells. SIRTl"7" THP-1 cells were infected as in (A) and treated with 5 μΜ SRT and 500 nM LysoTracker (LTR) for 4 hours before fixation. Quantification of LTR-positive BCG-GFP is shown. NS - not significant. *P< 0.05, by two-tailed Student's t- test.
[0018] Fig. 12 shows data illustrating that SRT1720 reduces tissue Mycobacterium tuberculosis load, reduces Mycobacterium tuberculosis derived lung pathology and that SIRTl deficient mice display an enhanced inflammatory response. (A) shows line graphs showing the change in bacillary load in lung and spleen of Mycobacterium tuberculosis infected mice. These mice were treated with 25, 50, or 100 mg/kg of SRT starting 7 days post-infection. Bacillary loads were enumerated on days 1, 7, 21, and 35 post-infection. Control - Untreated infected mice. (B) shows a column graph depicting the change in SIRTl expression in the lungs of Mycobacterium tuberculosis infected mice which were treated with 25, 50 or 100 mg/kg of SRT1720, starting 7 days post-infection. On day 35, RNA was extracted and SIRTl mRNA expression was assessed by qRT-PCR. Relative expression differences normalized to GAPDH expression are shown. UN - uninfected mouse, IN - Infected mouse. Data is a representative of two independent experiments. *P< 0.05 as determined using Student's t- test. (C) shows images showing the gross appearance of mouse lungs and spleens at day 35 post-infection from Mycobacterium tuberculosis infected mice, either untreated or treated with 100 mg/kg SRT1720 (SRT 100). (D) shows light micrographs of hematoxylin and eosin staining of lung sections on day 35 after infection from Mycobacterium tuberculosis infected mice, either untreated or treated with lOOmgkg SRT1720 (SRT 100). (E) shows column graphs depicting change in gene expression between wild type (WT) and Mac-SIRTl KO mice, which were infected with Mycobacterium tuberculosis. On day 21, RNA was extracted from the peritoneal cells and mRNA expression was assessed by qRT-PCR. Relative expression levels normalized to GAPDH are shown. Data is expressed as mean + SEM. n = 4 - 9 mice per group. *P < 0.05, **P < 0.01 as determined Mann-Whitney test.
[0019] Fig. 13 shows various two-parameter dot plots as examples of the staining performed for each antibody used for the mass cytometry analysis. To verify the functionality of each antibody, representative plots illustrating the expected staining profiles of each antibody are shown. Cells gated as shown (as annotated above each plot).
[0020] Fig. 14 shows a heat-plot summary of the average median expression of each cellular marker analysed for the 28 clusters identified via tSNE (see Fig. 6) and a rough description of each of the clusters. Samples from all mice across 4 groups (n = 15) were pooled and ran as a single sample.
[0021] Fig. 15 shows scatter plots and histograms outlining the manual gating strategy used in the analyses disclosed above. (A) shows scatter plots and histograms showing the sequential manual gating strategy of the gathered mass cytometry data in order to annotate the major clusters of lung cells. (B) shows scatter plots and cell population charts showing the fluorescent flow cytometric gating strategy used to validate changes in monocyte composition in the lungs of Mycobacterium tuberculosis infected mice upon SRT1720 treatment. Similar staining and gating strategy was used to assess the infiltrated myeloid cells in Mycobacterium tuberculosis infected Mac-SIRTl KO mice
[0022] Fig. 16 shows scatter plots depicting the strategy using in the validation of t- distributed stochastic neighbour embedding (tSNE) guided lung populations. (A) shows scatter plots depicting the validation of tSNE guided dendritic cell populations. tSNE-guided analysis identified three major subsets of dendritic cell population i.e. Clusters 7, 17 and 29 (refer to Figure 14). These clusters were overlayed on CDl lc+MHCII+ gated cells. Cluster 7 and 17 were found to express CDl lb and not CD103, whereas cluster 29 was found to express CD103 and not CDl lb marker. This confirms the authenticity of the clusters. (B) shows scatter plots depicting the validation of tSNE guided Ly6Cl0 lung population. tSNE- guided analysis identify 4 and 5 major subsets of Ly6Cl0 and Ly6C+ monocyte subsets, respectively (refer to Figure 14). CD1 lc'MHCIT cells were gated and Ly6C+ monocytes (five clusters) and Ly6G+ neutrophils were excluded. Ly6Cl0 clusters 8, 9, 18 and 19 are shown in bottom left square and ungrouped cells (remaining) are shown in top left and right square. CDl lb expression divides these 4 clusters in two groups with 8 and 9 together and 18 and 19 together. CD44 expression further separates cluster 8 and 9, whereas CD38 expression separates cluster 18 and 19.
[0023] Fig. 17 shows scatter plots and column graphs depicting the changes in lung myeloid cell population upon Mycobacterium tuberculosis infection and SRT1720 treatment. (A) shows scatter plots depicting the results of aggregate t-distributed stochastic neighbour embedding (tSNE) dimensionality, whereby reduced single cell data from lung tissues of mice analyzed are plotted and color-coded into the 28 'unsupervised' DensVM clusters. tSNE guided analysis of all four groups, Uninfected, infected, infected+SRT and uninfected+SRT is shown. A grouped description of each cluster is indicated. Each plot represents a pool of 3 to 4 replicate lung tissue cells. (B) shows column graphs depicting mass cytometry data that was analyzed using manual gating strategy (as described in Fig. 12A). Mean frequencies of dendritic cells (CDl lc+MHCII+) and its subset are shown in the lungs of uninfected (UN), infected (IN) and SRT1720 treated infected (IN+SRT) animals. (C) shows column graphs depicting the mean frequencies of CD64+MerTK+ macrophages (MQs), alveolar macrophages (AMs, CD64+MerTK+Siglec_F+) and Interstitial macrophages (IMs, CD64+MerTK+Siglec_F~) in mass cytometry data. (D) shows a bar chart depicting the differential cluster percentage of 6 clusters in uninfected (UN), Infected (IN) and SRT1720 treated infected (IN+SRT) animals. All these 6 clusters are differentially modulated by SRT1720 treatment (P< 0.05). "*" indicates significance between UN and IN; "+" indicates significance between IN and IN+SRT. Since no differences were found among UN and UN+SRT groups (Figure 5B), the data of uninfected and uninfected+SRT animals were grouped in a single group for this analysis and considered as uninfected (UN). (E) shows a column graph depicting percentage data of lung Ly6Clo/Ly6C+ CDl lbloF4/80+ monocytes in Mycobacterium tuberculosis infected WT (controls) and Mac-SIRTl KO mice on day 3 postinfection, as assessed using flow cytometry. (F) shows a column graph depicting flow cytometry data indicating percentage of CD45+CDl lc+ lung cells from Mycobacterium tuberculosis infected mice, either treated with SRT1720 or untreated. Data is expressed as mean + SEM. n = 4 - 6 mice per group. *P< 0.05, **P< 0.01, ***P< 0.001, +P< 0.05 as determined using Mann- Whitney test.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0024] The development of more accessible targets for combating persistent Mycobacterium tuberculosis infections in a host is important in the development of treatment methods for Mycobacterium tuberculosis infections. One way of tackling a persistent infection is ensuring an effective host immune response. This aspect is important for the containment of a persistent Mycobacterium tuberculosis infection, of which the metabolic programs of the host play a key role in modulating the host immune response. The engagement of cellular immuno -metabolic circuits are predominantly regulated by sensors, including, among others, mTOR (mammalian targets of rapamycin), and AMPK (AMP-activated protein kinase). Perturbations in mTOR and AMPK signalling have been associated with Mycobacterium tuberculosis virulence. Targeting the mTOR pathway with specific inhibitors has been shown to stimulate autophagy induction, leading to increased mycobacterial clearance. Similarly, activation of AMPK using the anti-diabetic drug metformin, lead to improved Mycobacterium tuberculosis control. This highlights the potential of targeting functional connections between host immune defence and metabolism to modulate Mycobacterium tuberculosis pathogenicity. [0025] The present invention shows that Mycobacterium tuberculosis downregulates sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, in monocytes / macrophages, tuberculosis animal models, and tuberculosis patients with active disease. Activation of SIRT1 reduced intracellular growth of drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, induced phagosome-lysosome fusion and autophagy in SIRT1 -dependent manner. SIRT1 activation dampened Mycobacterium tuberculosis mediated persistent inflammatory responses via deacetylation of RelA/p65, leading to impaired binding of RelA/p65 on the promoter of inflammatory genes. In Mycobacterium tuberculosis infected mice, use of SIRT1 activators ameliorated lung pathology, reduced chronic inflammation and enhanced efficacy of anti-tuberculosis drug. Mass Cytometry based high-dimensional analysis revealed SIRT1 activation mediated modulation of lung myeloid cells in Mycobacterium tuberculosis infected mice. Notably, myeloid cell-specific SIRT1 knockout mice display increased inflammatory responses and susceptibility to Mycobacterium tuberculosis infection. Collectively, these results provide a link between SIRT1 activation and tuberculosis pathogenesis, and indicate a potential of SIRT1 activators in designing an effective and clinically relevant host-directed therapies (HDTs) for tuberculosis.
[0026] In the present disclosure, it is shown that SIRTl expression is downregulated during active Mycobacterium tuberculosis infection, and that enhancement of SIRTl activity using specific activators inhibits the intracellular growth of Mycobacterium tuberculosis, normalizes the inflammatory response, enhances the efficacy of other compounds, for example isoniazid, a first-line anti-tuberculosis drug, and limits disease immunopathology.
[0027] Thus, the present invention provides a method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the method comprises administration of a compound which enhances activity of an NAD+-dependent deacetylase. As used herein, the term "NAD+-dependent deacetylase" refers to a class of proteins deacetylases, which are enzymes which have the ability to remove acetyl groups from lysine amino acids in the target proteins, whereby this activity is dependent on the presence or absence of nicotinamide adenine dinucleotide (NAD+). Other examples of NAD+- dependent protein deacetylases are, but are not limited to, histone deacetylases (HDACs) These protein deacetylases can be divided into various categories, classes I to IV, of which class III refers to NAD+-dependent protein deacetylases. Examples of class III NAD+- dependent protein deacetylases are, but are not limited to sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, and sirtuin 7.
[0028] As used herein, the term "sirtuin" stands for "silent mating type information regulation 2 homologs", and refers to a family of nicotinamide adenine dinucleotide (NAD+)- dependent class III histone deacetylases (HDACs), consisting of seven members (for example, sirtuin 1 to sirtuin 7 in humans), which are present in nearly all sub-cellular compartments. Different from other known protein deacetylases, which simply hydrolyse acetyl-lysine residues, sirtuin-mediated deacetylation requires the concomitant reaction of NAD hydrolysis in order to be able to deacetylate lysine, meaning to say that NAD+ is used as a co-factor in the reaction. Among the sirtuins, the protein sirtuin 1 (SIRTl) is involved in a range of cellular processes important in the maintenance of human health, including the stress response, cellular metabolism, and ageing. SIRTl is known to be important in the prevention of viral diseases; however, its role in chronic bacterial infections is unknown. Cytosolic functions of sirtuin 2 include the regulation of microtubule acetylation, control of myelination in the central and peripheral nervous system and gluconeo genesis. Sirtuin 3, sirtuin 4 and sirtuin 5 are located in mitochondria and regulate metabolic process and enzymes. Sirtuin 6 is a stress responsive protein deacetylase and is essential in post-natal development and survival. Sirtuin 7 localizes to nucleolus and interacts with RNA Polymerase I. Sirtuin 7 can attenuate DNA damage and thereby promote cellular survival under conditions of genomic stress. The enzymatic activities of sirtuins also include, and are not limited to, mono-adenosin triphosphate -ribosyltransferase, or deacylase activity, including desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. Thus, in one example, the compound is a sirtuin enhancer. In another example, the NAD+-dependent deacetylase is, but is not limited to, sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7, derivatives, homologues and combinations thereof. In another example, the NAD+- dependent deacetylase is sirtuin 1. As used herein, the term "homologue" refers to the existence of shared ancestry between genes (or structures) in different taxa. In other words, homology is the relationship between biological structures or sequences that are derived from a common ancestor and that ultimately have the same or similar functions (that is a biological equivalent). In terms of sequence homology, DNA or protein sequences are defined in terms of shared ancestry. The term "sequence homology" is often used in place of the term "sequence similarity", or vice versa. Thus, a sequence that is highly conserved (a conservative sequence) if it does not change or only shows minimal changes between the species. In the case of, for example sirtuin, SIRTl stands for "sirtuin (silent mating type information regulation 2 homolog) 1 (Saccharomyces cerevisiae)", referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (Saccharomyces cerevisiae) is Sir2.
[0029] Disclosed herein are compounds that act on the activity of the NAD+-dependent deacetylase. In other words, the compounds disclosed herein have the ability to increase the activity of the target proteins, in this case, the NAD+-dependent deacetylase, or, for example, at least one or more sirtuin proteins, that is any one or more of sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7. This also applies to derivatives and salts of the disclosed compounds. For example, it has been shown that SRT1720 specifically enhances SIRTl activity. It has also been shown that resveratrol has an effect on SIRTl and SIRT2. The compound SA3 has been shown to affect SIRTl. The compound BML-278 has been shown to have an effect on SIRTl (for example, with an EC50 = 1 μΜ), SIRT2 (for example, with an EC50 = 25 μΜ) and SIRT3 (for example, with an EC50 = 50 μΜ). In one example, the compound is, but is not limited to, N-[2-[3-(piperazin-l-ylmethyl)imidazo[2,l-b][l,3]thiazol- 6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N-cyclopentyl-2-diazenyl-l-(3- methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4-phenyl- l,4-dihydro-3,5-pyridinedicarboxylate (BML278), trans-3,5,4'-trihydroxystilbene (resveratrol); and salts and/or derivatives thereof. In one example, the compound is not resveratrol. In another example, the compound is, but is not limited to, N-[2-[3-(piperazin-l- ylmethyl)imidazo[2,l-b][l,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N- cyclopentyl-2-diazenyl-l-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4-phenyl-l,4-dihydro-3,5-pyridinedicarboxylate (BML278), and salts and/or derivatives thereof. In one example, the compound is N-[2-[3-(piperazin-l- ylmethyl)imidazo[2,l-b][l,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide (SRT1720) or a derivative thereof.
[0030] As used herein, the term "derivative" refers to a structural analogue of the compound in question. For example, a derivative can be, but is not limited to, a salt, an isomer, a tautomer, a prodrug or a pharmaceutically accepted version of the compound.
[0031] Specific methods of the invention further comprise the administration of an additional therapeutic agent (that is, a therapeutic agent other than a compound of the invention) or a further therapy. In certain examples, the compound(s) can be used in combination with at least one other therapeutic agent. In another example, the compound(s) can be used in combination with at least one other therapy (also known as combination therapy). In yet another example, the compound(s) can be used in combination with at least one other treatment regime. Therapeutic agents include, but are not limited to antibiotics, anti-emetic agents, anti-depressants, and antifungal agents, anti-inflammatory agents, antiviral agents, anti-cancer agents, anti-microbial agents, anti-tuberculosis agents, immunomodulatory agents, alpha-interferons, β-interferons, alkylating agents, hormones or cytokines. In another example, the invention encompasses administration of at least one or more additional therapeutic agent(s) that demonstrates anti-tuberculosis activity. In another example, the combination therapy comprises chemotherapy.
[0032] The compounds of the invention and the other therapeutics agent can act additively or, preferably, synergistically. In one example, a composition comprising a compound disclosed herein is administered concurrently with the administration of another therapeutic agent, which can be part of the same composition or in a different composition from that comprising the compounds of the invention. In another example, a compound of the invention is administered prior to, together with, sequentially or subsequent to administration of another therapeutic agent. In another example, a compound as disclosed herein is administered to a patient who has not previously undergone or is not currently undergoing treatment with another therapeutic agent. In yet another example, a compound as disclosed herein is administered to a patient who has previously undergone or is currently undergoing treatment with another therapeutic agent. In one example, the method, as disclosed herein, refers to the administration of one or more compounds, as described herein, without an additional therapeutic agent.
[0033] Disclosed herein are methods and compounds for treating mycobacterial infections in a host. The term "mycobacterial" refers to infections resulting from an initial infection and the resulting propagation of mycobacteria in a host. Mycobacterium is a genus of bacteria from the family Mycobacteriacea. The bacterial agents from the genus Mycobacterium include, but are not limited to, M. africanum, M. bovis, M. bovis BCG, M. canetti, M. caprae, M. microti, M. mungi, M. orygis, M. pinnipedii, M. suricattae, M. tuberculosis, all of which form the so-called Mycobacterium tuberculosis complex, which is a grouping of causative agents of human and animal tuberculosis; as well as M. avium, M. avium paratuberculosis, M. avium silvaticum, M. avium "hominissuis" , M. colombiense, M. indicus pranii, which form the so-called Mycobacterium avium complex; M. asiaticum, M. gordonae, M. gastri, M. kansasii, M. hiberniae, M. nonchromogenicum, M. terrae, M. triviale, M. ulcerans (a known of the "Buruli", or "Bairnsdale" ulcer), M. pseudoshottsii, M. shottsii, M. triplex, M. genavense, M. florentinum, M. lentiflavum, M. palustre, M. kubicae, M. parascrofulaceum, M. heidelbergense, M. interjectum, M. simiae, M. bohemicum, M. botniense, M. branderi, M. celatum, M. chimaera, M. conspicuum, M. cookie, M. doricum, M. farcinogenes, M. haemophilum, M. heckeshornense, M. intracellulare, M. lacus, M. leprae (a known cause of leprosy), M. lepraemurium M. lepromatosis (another, less significant, cause of leprosy), M. liflandii, M. malmoense, M. marinum, M. monacense, M. montefiorense , M. murale, M. nebraskense, M. saskatchewanense , M. scrofulaceum, M. shimoidei, M. szulgai, M. tusciae, M. xenopi, M. yongonense, M. intermedium, M. abscessus, M. chelonae, M. bolletii, M. fortuitum, M. fortuitum subsp. Acetamidolyticum, M. boenickei, M. peregrinum, M. porcinum. M. senegalense, M. septicum, M. neworleansense, M. houstonense, M. mucogenicum, M. mageritense, M. brisbanense, M. cosmeticum, M. parafortuitum, M. austroafricanum, M. diernhoferi, M. hodleri, M. neoaurum, M. frederiksbergens, M. aurum, M. vaccae, M. chitae, M. fallax, M. confluentis, M. flavescens, M. madagascariense, M. phlei, M. smegmatis, M. goodie, M. wolinskyi, M. thermoresistibile , M. gadium, M. komossense, M. obuense, M. sphagni, M. agri, M. aichiense, M. alvei, M. arupense, M. brumae, M. canariasense, M. chubuense, M. conceptionense , M. duvalii, M. elephantis, M. gilvum, M. hassiacum, M. holsaticum, M. immunogenum, M. massiliense, M. moriokaense, M. psychrotolerans, M. pyrenivorans, M. vanbaalenii, M. pulveris, M. arosiense, M. aubagnense, M. chlorophenolicum, M. fluoroanthenivorans, M. kumamotonense, M. novocastrense, M. parmense, M. phocaicum, M. poriferae, M. rhodesiae, M. seoulense, and M. tokaiense, whereby the term "M." stands for Mycobacterium. Various species and strains can be grouped together, for example, according to the growth rate of the mycobacteria, or according to their microscopic appearance (for example, microbiological characteristics, structural appearances, and staining). The latest approach is to group strains and species using cladistics, which is the classification of organisms based on the group's most recent ancestor in combination with, for example, comprehensive phylogenetic analysis based on genetic alignments of core genomes of bacterial strains. The various species can also be grouped together according to their pathogenicity (for example, pathogenic and non- pathogenic), as well as the diseases which they cause (for example, human and animal tuberculosis is caused by the bacteria listed in the Mycobacterium tuberculosis complex (MTBC)). In one example, the mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium ajricanum, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium leprae, Mycobacterium avium, Mycobacterium paratuberculosis and Mycobacterium pinnipedii. In another example, the mycobacterium is a causative agent of tuberculosis. In yet another example, the mycobacterium is a drug -resistant mycobacterium. In a further example, the mycobacterium is a multidrug-resistant (MDR) or extensively drug- resistant (XDR) mycobacterium. As used herein, the term "drug-resistance" refers to the capability of organisms, usually pathogens, to "acquire" (that is, to evolve) a resistance to the drug used against them, therefore reducing the drug's effectiveness as, for example, an antimicrobial, anti-helminthic or an anti -neoplastic in treating and/or curing a disease or condition caused by said pathogen. When an organism is resistant to more than one drug, the organism is then said to be multidrug-resistant (MDR). The term "extensively drug-resistant (XDR)" refers to types of drug-resistant pathogens that have become resistant to almost all known forms of treatment for that particular pathogen. For example, in the case of tuberculosis, multi-drug resistant is used to describe a tuberculosis pathogen that is resistant to at least isoniazid and rifampin, at present the two most potent and most commonly prescribed tuberculosis drugs. Extensively drug-resistant tuberculosis is a form of multidrug- resistant tuberculosis which is resistant to isoniazid and rifampin, as well as fluoroquinolone and at least one of three injectable second-line tuberculosis drugs (for example, but not limited to amikacin, kanamycin, or capreomycin). Therefore, in one example, the antituberculosis drug (also known as a tuberculosis drug) can be, but is not limited to, amikacin, aminosalicylic acid, bedaquiline, capreomycin, cycloserine, delamanid ethambutol, ethionamide, fluoroquinolone, fluoroquinolone antibiotic, isoniazid (INH), kanamycin, levofloxacin, linezolid, moxifloxacin, oxafloxacin, (6S)-2-nitro-6-{ [4- (trifluoromethoxy)benzyl]oxy } -6,7-dihydro-5H-imidazo[2, l-b] [ 1 ,3]oxazine (pretomanid; PA824), pyrazinamide, rifampin, rifampicin, rifabutin, streptomycin, and combinations thereof. In another example, the anti-tuberculosis drug is a combination of isoniazid (INH) and rifampin. In a further example, the anti-tuberculosis drug is isoniazid (INH). In yet another example, the anti-tuberculosis drug is a combination of isoniazid, rifampin and fluoroquinolone. In another example, the anti-tuberculosis drug is a combination of isoniazid, rifampin, fluoroquinolone and at least one of amikacin, kanamycin, and/or capreomycin.
[0034] In terms of the combination therapy, the dose of the further drug or treatment used in combination with the compounds claimed herein depends on the nature of the treatment to be given. In any case, the dose of a further drug that is administered to the subject or patient is to be in an effective amount, that is an amount effective to achieve the desired results, which is the treatment, prevention or inhibition of the disease in question. Based on this criteria, as a person skilled in the art will appreciated, the actual dose of a further drug or therapy may vary depending on, for example, the weight, metabolism, underlying medical conditions, contraindications, the length of treatment, the severity of the disease to be treated and the like. Thus, in one example, the further drug is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg, between about 1 mg/kg to about 5 mg/kg, between about 2.5 mg/kg to about 8 mg/kg, between about 6 mg/kg to about 12 mg/kg, between about 8 mg/kg to about 14 mg/kg; between about 7 mg/kg to about 11 mg/kg; between about 9.5 mg/kg to about 12 mg/kg and between about 10.5 mg/kg to about 15 mg/kg of the body weight of the patient. In another example, the further drug is an antituberculosis drug, which is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg, between about 1 mg/kg to about 5 mg/kg, between about 2.5 mg/kg to about 8 mg/kg, between about 6 mg/kg to about 12 mg/kg, between about 8 mg/kg to about 14 mg/kg; between about 7 mg/kg to about 11 mg/kg; between about 9.5 mg/kg to about 12 mg/kg and between about 10.5 mg/kg to about 15 mg/kg of the body weight of the patient. In a further example, the anti-tuberculosis drug is administered at a concentration ranging from 5mg/kg to 20 mg/kg. In the example of an anti-tuberculosis drug, the concentration administered to the patient may also vary, depending on whether the infection to be treated is a latent or active infection. Thus, in one example, the dose administered to the patient is 5 mg/kg for a patient deemed to have an active tuberculosis infection. In another example, the dose administered to the patient is between 10 mg/kg to 20 mg/kg for a patient deemed to have a latent tuberculosis infection.
[0035] The compounds disclosed herein can be administered to provide systemic distribution of the compound within the patient. In one example, the compound(s) disclosed herein are administered to produce a systemic effect in the body. In another example, the compounds disclosed herein are administered directly to the site affected by the condition, as, for example to the lung or the infected areas, using the requisite means, which will be apparent to a person skilled in the art. In another example, the compounds disclosed herein are administered systemically, via oral, mucosal (including sublingual, buccal, rectal, nasal, or vaginal), parenteral (including subcutaneous, intramuscular, bolus injection, intra-arterial, or intravenous), transdermal, or topical administration. In one example, the compounds are administered intravenously. In another one example, the compounds disclosed herein are administered via oral administration. In another example, the compounds disclosed herein are not administered via oral administration.
[0036] The compounds disclosed herein are to be administered to the patient in an effective amount. To this end, as a person in the art will appreciate, the dosage to be administered to a patient would depend on, and be influenced by, different variables, for example, the weight, metabolism, underlying medical conditions, contraindications, the length of treatment, the severity of the disease to be treated and the like. In one example, the compound is administered at a concentration ranging from between about 1 mg/kg to 2000 mg/kg (2 g/kg), between about 5 mg/kg to about 25 mg/kg, between about 10 mg/kg to about 15 mg/kg, between about 1.6 mg/kg to 35 mg/kg, between about 25 mg/kg to about 60 mg/kg, between about 50 mg/kg to about 150 mg/kg, between about 100 mg/kg to about 300 mg/kg, 100 mg/kg to about 2000 mg/kg (2 g/kg), between about 200 mg/kg to about 500 mg/kg, between about 250 mg/kg to about 800 mg/kg; between about 400 mg/kg to about 1000 mg/kg (1 g/kg); between about 600 mg/kg to about 1200 mg/kg (1.2 g/kg) and between about 700 mg/kg to about 1500 mg/kg (1.5 g/kg) of the body weight of the patient. In one example, the compound is administered at a concentration of 10 mg/kg, or 50 mg/kg, or 100 mg/kg, or 500 mg/kg, or 25 mg/kg. It will be appreciated by a person skilled in the art that dosage concentrations determined using animal models, for example murine, porcine, or non-human primates may not exactly translate to the same dosage in humans, due to the obvious differences in anatomy and metabolism. Thus, for example, a dose of 100 mg/kg used in a murine model may result in a dose of roughly 500 mg/day for a 60 kg human. It is understood that a person skilled in the art is capable of extrapolating the required dose, for example for a human subject from, for example, data gathered from a mouse model.
[0037] The composition, shape, and type of dosage forms of the invention will typically vary depending on their use. For example, a dosage form used in the acute treatment of a disease or a related disease may contain larger amounts of one or more of the active ingredients it comprises than a dosage form used in the chronic treatment of the same disease. Similarly, a parenteral dosage form may contain smaller amounts of one or more of the active ingredients it comprises than an oral dosage form used to treat the same disease or disorder. These and other ways in which specific dosage forms encompassed by this disclosure will vary from one another will be readily apparent to those skilled in the art. Thus, different therapeutically effective amounts may be applicable for different conditions, as will be readily known by those of ordinary skill in the art. Similarly, amounts sufficient to treat or prevent such conditions, but insufficient to cause, or sufficient to reduce, adverse effects associated with conventional therapies are also encompassed by the above described dosage amounts and dose frequency schedules.
[0038] The compounds disclosed herein are to be administered to a patient suffering from, or suspected to suffer from, a mycobacterial infection. An infection is generally understood to be the infiltration and proliferation of a foreign organism, in most cases a pathogenic or an infectious organism, into and within a host, or a patient, as the case may be. Infections can be caused by infectious agents including, but not limited to, viruses, viroids, prions, bacteria, nematodes (for example, parasitic roundworms and pinworms), arthropods (for example, ticks, mites, fleas, and lice), fungi (for example ringworm), and other macro-parasites such as tapeworms and other helminths. In one example, the host is infected with bacteria. In another example, the bacterium is mycobacterium. Infections can either subclinical (also known as a latent, silent, occult or inapparent infection) or clinical (also known as an active or apparent infection), depending on the absence or presence of symptoms other than the presence of the infectious agent. Therefore, a host is considered to have a latent infection when the presence of the infectious agent in the host is known but the host does not present any further symptoms. Examples of a latent bacterial infection are, but are not limited to, latent tuberculosis and latent viral infections, for example by viruses of the Herpesviridae family. In one example, the patient has a latent infection. In another example, the patient has an active infection. In a further example, the patient has a latent tuberculosis infection. In another example, the patient has an active tuberculosis infection. The term "acute" in conjunction with infection is generally used to denote a short-term infection, whereas the term "chronic" is used to denote a long-term infection. The word "infection" is often used to denote any presence of a particular pathogen at all (no matter how little the amount), but is also often used to imply a clinically apparent infection, that is a case of infectious disease. Thus, the term "infection" can also be replaced by the term "colonization" when referring to the situation of a latent infection, that is the situation where pathogens are present but no clinically apparent infection (no disease) is present.
[0039] Also disclosed herein is the use of a compound which enhances activity of an NAD+-dependent deacetylase in the manufacture of a medicament for preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof. In one example, there is disclosed a compound for use in preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the compound enhances activity of an NAD+-dependent deacetylase. In another example, there is disclosed a sirtuin enhancer for use in preventing, treating or preventing intracellular mycobacterial infections. The terms "treat", "treatment", and grammatical variants thereof, refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological condition, disorder or disease or obtain beneficial or desired clinical results. Such beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of extent of condition, disorder or disease; stabilized (i.e. not worsening) state of condition, disorder or disease; delay or slowing of condition, disorder or disease progression; amelioration of the condition, disorder or disease state, remission (whether partial or total), whether detectable or undetectable; or enhancement or improvement of condition, disorder or disease. Treatment includes eliciting a cellular response that is clinically significant, without excessive levels of side effects. Treatment also includes prolonging survival as compared to expected survival if not receiving treatment.
[0040] The invention illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms "comprising", "including", "containing", etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the inventions embodied therein herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention.
[0041] The invention has been described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.
[0042] Other embodiments are within the following claims and non- limiting examples. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.
EXPERIMENTAL SECTION
Mycobacterium tuberculosis infection downregulates SIRT1 expression
[0043] Understanding host immune signalling pathways and Mycobacterium tuberculosis evasion strategies are warranted for the advancement of tuberculosis host-directed therapies (TB HDTs). This led to the investigation of the effect of Mycobacterium tuberculosis infection on sirtuins, an important family of host energy sensors, also known to regulate inflammation. A comparison of Mycobacterium tuberculosis infected and uninfected human monocytic THP-1 cells revealed a time-dependent Mycobacterium tuberculosis mediated downregulation of SIRT1 (Fig. 7 A), the gene that encodes for sirtuin 1 (SIRT1), which was confirmed by qRT-PCR and immunoblot (Fig. 1, A and B), and is consistent with published microarray datasets of Mycobacterium tuberculosis infected cells (Fig. 7, B and C). A time- dependent reduction of SIRT1 mRNA expression was also observed in the lung tissues of Mycobacterium tuberculosis infected mice (Fig. 1C). Higher SIRT1 expression was observed in the lesions of Mycobacterium tuberculosis infected macaques with latent tuberculosis compared with active disease (Fig. ID). Immunostaining of the granulomas of Mycobacterium tuberculosis infected macaque lung sections further showed higher levels of SIRT1 in the Bacillus Calmette-Guerin (BCG)-vaccinated macaques compared with unvaccinated animals (Fig. 1, E and F). These SIRT1 expressing cells were mainly CD68+ and CD163+ macrophages and not CD3+ T cells (Fig. 8). [0044] To evaluate the clinical significance of Mycobacterium tuberculosis mediated SIRTl downregulation, a pairwise comparison of SIRTl mRNA expression profiles derived from peripheral blood of active tuberculosis patients, latent tuberculosis individuals, and healthy controls from seven different cohorts (Table 2) was performed. In the UK' IO and SA' 10 cohort, SIRTl mRNA levels were lowest in active tuberculosis patients compared with healthy and latent tuberculosis individuals (Fig. 1G). Lower expression of SIRTl mRNA in active tuberculosis individuals was also observed in the SA' 13 cohort (Fig. 7D). Notably, SIRTl mRNA levels were also reduced in HIV patients with tuberculosis as comorbidity, compared to those with HIV alone (SA' 14 cohort; Fig. 1G). In three additional data sets from tuberculosis patients undergoing anti- tuberculosis chemotherapy, SIRTl mRNA increased after two to three months of therapy and reached levels comparable with those observed in healthy/latent tuberculosis individuals by the sixth month of treatment (Fig. 1H and Fig. 7, E and F). Furthermore, human monocyte-derived macrophages (hMDMs) from tuberculosis patients also displayed reduced SIRTl mRNA expression compared with those from latent tuberculosis individuals (Fig. 7G). This data highlights an important functional consequence of downregulation of SIRTl expression during Mycobacterium tuberculosis infection in humans. In all, these results indicate (i) an important disease-related effect of Mycobacterium tuberculosis infection on SIRTl expression and (ii) an association of lower SIRTl expression with tuberculosis pathogenesis.
SIRTl activation restricts intracellular Mycobacterium tuberculosis growth, and induces phagosome-lysosome fusion and autophagy
[0045] To determine if SIRTl is essential for controlling mycobacterial growth, SIRTl -deficient cells were infected with Mycobacterium tuberculosis and were found to display higher bacillary loads compared with wild-type controls (Fig. 2A), suggesting that activating SIRTl may control mycobacterial growth. SIRTl activity can be enhanced by resveratrol (trans-3,5,4'-trihydroxystilbene; RES; a natural activator) and SRT1720 (N-[2-[3- (piperazin- l-ylmethyl)imidazo[2, 1 -b] [ 1 ,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide; SRT; a synthetic activator). Indeed, enhancing SIRTl activity by resveratrol and SRT1720, using concentrations that are not toxic for cells (Fig. 9, A and B), inhibited the growth of intracellular Mycobacterium Bacillus Calmette-Guerin (Fig. 9C) and Mycobacterium tuberculosis in THP-1 cells in a dose- and time-dependent manner (Fig. 2, B-D). SRT1720 treatment also inhibited the growth of intracellular Mycobacterium Bacillus Calmette-Guerin in human monocyte-derived macrophages (hMDMs; Fig. 9D). This effect was abolished in cells where SIRT1 was genetically inactivated (Fig. 2E) or chemically inhibited (Fig. 9E). Resveratrol and SRT1720 treatment also restricted intracellular replication of multi-drug resistant strains of Mycobacterium tuberculosis in a time-dependent manner (Fig. 2F). Inhibition of mycobacterial growth by SIRT1 activation was further validated with N- cyclopentyl-2-diazenyl-l-(3-methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), an additional SIRT1 activator (Fig. 9F). SIRT1 activity is primarily dependent on the availability of intracellular NAD+. In the experiments, Mycobacterium tuberculosis infection reduced the intracellular NAD+/NADH ratio, which was reversed by the addition of SIRTl - activating compounds (Fig. 9G). Notably, SRT1720-mediated activation increased the levels of SIRT1 mRNA in Mycobacterium tuberculosis infected cells (Fig. 9H), consistent with earlier studies.
[0046] To identify the possible mechanism(s) underlying the restriction of intracellular Mycobacterium tuberculosis growth by SIRT1 activators, a genome-wide transcriptional analysis using total RNA isolated from Mycobacterium tuberculosis infected THP-1 cells in the presence or absence of resveratrol was performed. At 24 hours post-infection, a total of 8766 genes were differentially expressed in response to infection (Fig. 10A). Resveratrol treatment altered the expression of 6325 genes compared with untreated Mycobacterium tuberculosis infected cells (Fig. 10A), of which 71% (4486/6325) overlapped with those affected by infection. Notably, resveratrol reversed the expression pattern of 3062 of these genes (Quadrant X and Y in Fig. 10B and Table 3). Analysis of these 3062 genes identified the enrichment of genes that regulate autophagy and phagosome-lysosome fusion (P = 4.76xl0"5), indicating induction of innate anti-microbial cellular functions (Fig. 2G). Indeed, in mycobacteria-infected cells, SRT-mediated SIRTl activation induced autophagy as assessed by upregulation of the autophagy-associated marker protein MAP1LC3A (LC3; Fig. 2H and Fig. 11A) and generation of its lipidated form (Fig. 21). This SRT-mediated autophagy induction was not observed in Mycobacterium tuberculosis infected SIRTl deficient cells (Fig. 2, H and I). Next, the effects of SIRTl activation on phagosome - lysosome fusion was assessed in cells infected with fluorescent Mycobacterium Bacillus Calmette-Guerin and stained with the lysosomal marker LysoTracker red (LTR). SIRTl activation by SRT1720 or resveratrol led to a significant increase in fluorescent Mycobacterium Bacillus Calmette-Guerin accumulation in LTR-labelled compartments (Fig. 2, J and K; Fig. 11, B and C), whereas this was not observed in cells where SIRT1 was chemically (Fig. 2, J and K) or genetically (Fig. 11D) inhibited. Taken together, this data indicates that SIRT1 activation contributes to the control of mycobacterial growth by inducing autophagy and phagosome-lysosome fusion.
SIRT1 activation normalize Mycobacterium tuberculosis -induced inflammatory responses by deacetylating RelA/p65
[0047] SIRT1 is a master regulator of chromatin remodelling and thus reprograms gene expression. To identify the effect of SIRT1 activation, Gene Ontology (GO) analysis was performed on 3062 resveratrol modulated genes in Mycobacterium tuberculosis infected cells (Fig. 10A). This indicated enrichment of GO processes involved in the inflammatory response, DNA damage restoration, telomere maintenance, and viral defence responses (Fig. 3, A and B, and Table 4). A similar trend was observed when the 3062 genes were analysed using Ingenuity Pathway Analysis (IPA). Pathways, such as triggering receptors expressed by myeloid cells (TREM)-l signalling, liver-X-receptor (LXR) activation, activation of interferon regulatory factors (IRF) by pattern recognition receptors (PRR), interferon signalling, and notably, NF-κΒ signalling, were associated with host cell genes upregulated by infection and downregulated by resveratrol (Fig. IOC and Table 5). This data suggests that resveratrol-mediated SIRT1 activation results in the normalization of genes and pathways that are modulated by Mycobacterium tuberculosis. Consistent with the effects of resveratrol on the inflammatory response, treatment of Mycobacterium tuberculosis infected THP-1 cells with SRT1720 reduced mRNA and protein expression of inflammatory cytokines (T Fa, ILlp, IL6, and MCP-1; Fig. 3, C and D), and RelA/p65 (Fig. 3, E-G), which is a subunit of NF-κΒ, a known target of SIRT1. Here, SRT treatment led to decreased RelA/p65 acetylation in Mycobacterium tuberculosis infected THP-1 cells (Fig. 3, F and G). Chromatin immunoprecipitation (ChIP) assays on infected and uninfected THP-1 cells revealed that Mycobacterium tuberculosis infection enhanced the occupancy of RelA/p65 on TNFa, IL1B, IL6, and MCP-1 promoters, which was reversed by SRT-mediated SIRT1 activation (Fig. 3H). These results indicate that SIRT1 activation mediated deacetylation of RelA/p65 is important for the unoccupancy of RelA/p65 on the promoter of pro- inflammatory genes, leading to the attenuation of Mycobacterium tuberculosis-induced inflammatory responses.
SIRT1 activation reduces Mycobacterium tuberculosis growth in mice
[0048] To determine if SIRT1 is essential for controlling mycobacterial growth in vivo, SIRT1 -deficient mice (myeloid cell-specific SIRT1 knockout; Mac-SIRTl KO) were infected with Mycobacterium tuberculosis and were found to display higher bacillary loads compared with wild-type controls (Fig. 4A). Next, the efficacy of resveratrol and SRT1720 in mouse models of acute and chronic tuberculosis was evaluated. In an acute model of Mycobacterium tuberculosis infection, resveratrol and SRT1720 inhibited the growth of Mycobacterium tuberculosis in the lungs and spleens of infected mice (Fig. 4, B and C, and Fig. 12A). When SRT1720 was administered in combination with isoniazid (INH), a greater proportion of mice with no detectable colony-forming units (CFU) in the tissues were detected compared with mice receiving isoniazid alone (Table 1). Consistent with findings in vitro (Fig. 9H), an increase in SIRT1 mRNA levels in the lungs of Mycobacterium tuberculosis infected mice upon SRT1720 treatment was also observed (Fig. 12B). In a chronic model of tuberculosis, SRT1720 alone inhibited the growth of Mycobacterium tuberculosis in the lungs (Fig. 4D), and mice treated with isoniazid in combination with SRT1720 showed decreased bacillary loads in the lungs compared with mice receiving isoniazid alone (Table 1). These results indicate that activation of SIRTl controls Mycobacterium tuberculosis growth and can enhance Mycobacterium tuberculosis clearance by anti-tuberculosis drugs, indicating the potential of SIRTl activators as adjunctive host-directed therapies for tuberculosis.
SIRTl activators reduce Mycobacterium tuberculosis mediated tissue pathology and inflammation in mice
[0049] Next, the effect of resveratrol and SRT1720 treatment on tissue immunopathology was assessed. Histologic examination of the lungs from untreated control mice at 35 days post-infection revealed diffuse coalescent lesions with numerous infiltrating macrophages and lymphocytes, and large number of intracellular acid-fast bacilli (AFB; Fig. 5A). At this time, resveratrol-treated mice displayed reduced levels of acid-fast bacilli and slightly smaller granulomatous lesions (Fig. 5A), previously linked with improved Mycobacterium tuberculosis control in mice. This observation was confirmed by morphometric analysis, which showed the reduced percentage of total lung parenchyma area involved in the pathology in resveratrol-treated mice compared with untreated control animals (43.8% vs. 55.6%, respectively; Fig. 5B). Similarly, tissues (lung and spleen) of SRT1720-treated Mycobacterium tuberculosis infected mice were smaller (Fig. 12C) and had lower levels of cellular infiltrate present (Fig. 1 ID), with a reduced percentage of total area of lung involved compared with untreated mice (33.7% vs. 44.3%, respectively; Fig. 5C). Consistent with in vitro findings (Fig. 3C), SRT1720 treatment reduced both mRNA and protein expression of inflammatory cytokines and chemokines in Mycobacterium tuberculosis infected lung tissue (Fig. 5, D and E). In contrast, Mycobacterium tuberculosis infected Mac-SIRTl KO mice showed increased expression of inflammatory cytokines and chemokines compared to wild- type mice (Fig. 5, F and G; Fig. 12E). Increased inflammation in the adipose tissues of Mac- SIRTl KO mice was also recently observed when given a high-fat diet. Taken together, these results emphasize the role of SIRTl in regulating immunopathology during Mycobacterium tuberculosis infection, possibly linked to SIRTl activation mediated control of Mycobacterium tuberculosis growth.
SIRTl activation modulates the lung myeloid landscape in Mycobacterium tuberculosis infected mice
[0050] Infiltration of myeloid cells expressing inflammatory cytokines and chemokines into the infected tissues is a major characteristic of tuberculosis progression in mice. Because reduced pathological inflammation was observed in the lungs of resveratrol- and SRT1720- treated Mycobacterium tuberculosis infected mice (Fig. 5), the profile of pulmonary myeloid cells was investigated using cytometry by time-of-flight (CyTOF). Lung cells from infected and uninfected mice, with or without SRT1720 treatment, were stained with a panel of 37 markers (Table 6) and analysed by mass cytometry. First, the panel antibodies were verified by their ability to bind to the lung cells (Fig. 13). Analysis of CD45+CD90"CD3"CD19" lung cells using non-linear dimensionality reduction (tSNE) in conjunction with a machine- learning updated clustering algorithm (DensVM) identified 28 distinct cell clusters with shared surface marker expression characteristics (Fig. 6A and Fig. 14). The accuracy of the machine-learning automated gating was assessed in experiments by validating each cluster using manual gating (Fig. 15 A), overlaying each cluster on its respective parent population. For example, dendritic cells (DCs) clusters (cluster 7, 17, and 29; Fig. 14), when overlaid on the gated CDl lc+MHCII+ population, were distributed according to CDl lb and CD 103 expression (Fig. 16A). Similar results were obtained when four Ly6Cl0 and five Ly6C+ clusters (Fig. 14) were assessed for Ly6C expression (Fig. 16B). All four Ly6Cl0 clusters (Clusters 8, 9, 18, and 19) were further categorized into individual clusters based on CDl lb, CD44, and CD38 expression (Fig. 16B), as identified by tSNE analysis (Fig. 6A and Fig, 14).
[0051] Unbiased analysis of 28 clusters clearly distinguished uninfected, infected, and SRT1720-treated infected animals (Fig. 6B and Fig. 17A). Nineteen out of 28 clusters were found to be significantly enriched or depleted in Mycobacterium tuberculosis infected animals (Fig. 6B). These differentiated clusters included diverse phenotypes, i.e., Ly6C+ (Cluster 23, 24, and 25) and Ly6Cl0 (Cluster 9, 18, and 19) monocytes; CDl lb+ dendritic cells (Cluster 7); plasmacytoid DCs (Cluster 11); CD64+MerTK+Siglec-F" interstitial macrophages (Clusters 13, 15, and 20); Ly6G+ neutrophils (Clusters 4 and 10); eosinophil's (Cluster 1); and innate lymphoid like cells (ILCs; Clusters 21 and 34) (Fig. 6, A and B and Fig. 14). The differential abundance of these cell subsets was confirmed using manual gating (Fig. 6C and Fig. 17, B and C). SRT1720 treatment had minimal effect on uninfected animals as indicated by mixed clustering of cells from uninfected animals, with or without SRT1720 treatment (Fig. 6B).
SIRT1 activation impairs Ly6C monocytes in the mice lung
[0052] High dimensional analysis revealed that SRT1720 treatment of Mycobacterium tuberculosis infected animals normalized 6 out of the 19 disease-associated clusters towards the frequency present in the lungs of uninfected mice (Fig. 6, B and D). Phenotyping of these six clusters identified them as Ly6CloCDl lbloF4/80+ monocytes (Cluster 18 and 19); Ly6C+CDl lbloF4/80+ monocytes (Cluster 23); Ly6G+CDl lbl0 neutrophils (Cluster 10); CD25+CDl lb+Sca-l+ innate lymphoid cells (Cluster 21); and Siglec-F+ eosinophil's (Cluster 1) (Fig. 6D and fig. S I ID). Of particular interest was the decreased abundance of CDl lbloF4/80+ monocytes (Ly6Cl0 or Ly6C+) in the lungs of SRT1720-treated Mycobacterium tuberculosis infected mice compared with untreated Mycobacterium tuberculosis infected mice, confirmed by manual gating (Fig. 6E), and verified using fluorescence flow cytometry (Fig. 6, F and G and Fig. 15B). In contrast, Mycobacterium tuberculosis infected Mac-SIRTl KO mice displayed an increased percentage and numbers of CD1 lbloF4/80+ (Ly6Cl0 or Ly6C+) monocytes in the lung compared with wild-type mice as early as 3 days post-infection (Fig. 17E and Fig. 6H, respectively). In the flow cytometry experiment, a reduced frequency of CD45+CDl lc+ cells (Fig. 17F) was noted in the lungs of SRT1720-treated Mycobacterium tuberculosis -infected mice compared with untreated mice, which was also apparent in the CyTOF experiments (i.e. CD45+CDl lc+ dendritic cells, Fig. 17B). This is consistent with an earlier study that shows SIRT1 mediated regulation of CD 11c expression. Overall, the data indicates an association of SIRT1 activity/expression with myeloid cell frequency in the lungs of Mycobacterium tuberculosis infected mice, relevant for the control of Mycobacterium tuberculosis growth and inflammation. [0053] Mycobacterium tuberculosis has co-evolved with the human immune system, acquiring a remarkable ability to exploit cellular host factors and circumvent immunity for its own survival. In this study, it was shown that active Mycobacterium tuberculosis infection suppresses SIRT1 (a conserved mammalian NAD+-dependent deacetylase) expression and reduce cellular NAD+ pool, which is required for SIRT1 activity. Depletion of cellular NAD+ could be due to a toxin secreted by Mycobacterium tuberculosis that leads to host cell death and Mycobacterium tuberculosis dissemination. It was shown that SIRT1 -activating compounds inhibited the intracellular growth of Mycobacterium tuberculosis; activated host cell autophagy and phagosome-lysosome fusion; and reduced Mycobacterium tuberculosis growth, tissue pathology, and chronic inflammation in mice. These effects are biologically significant responses that indicate clinically significant effects of SIRT1 activators in human tuberculosis. SIRT1 have been described to play a role in the regulation of autophagy and can also directly affect AMPK activity, which has been shown to be clinically beneficial. Thus, the capacity of both SIRT1 and AMPK to modulate innate immune mechanism and inflammation, emphasizes the importance of the SIRT1-AMPK axis in, (i) rewiring the host anti-microbial arsenal, and (ii) skewing the immuno-pathological balance towards protective immunity against Mycobacterium tuberculosis, leading to enhanced host benefits.
[0054] Tuberculosis pathogenesis is associated with early infiltration of myeloid cells into infected tissues. Inconsistencies in the naming and working definitions of myeloid cell subsets have complicated the objective description and quantification of cellular innate immune responses. Moreover, inflammatory conditions can dramatically change expression of many defining markers in activated cells. Utilizing a previously described unbiased high- dimensional analysis, the myeloid compartment in the lungs of Mycobacterium tuberculosis infected mice and found that SIRTl activation modulated the infiltration of a particular subset of Ly6Cl0/Ly6C+ CDl lbloF4/80+ monocytes. Cells fitting this description are important for early pathogen defence but, if sustained, can contribute to higher bacterial burdens and accelerate mortality in mice. Moreover Mycobacterium tuberculosis persist and disseminate by infecting newly recruited uninfected monocytes / macrophages, therefore reduced recruitment of Ly6C+/1° cells in SRT1720 treated Mycobacterium tuberculosis infected mice could also favour SRT1720 mediated Mycobacterium tuberculosis control. The recruitment of Ly6C monocytes into the tissues occurs via engagement of the chemokine receptor CCR2 with MCP-1 (CCL2), a chemokine regulated by SIRTl. In addition, mass cytometry data also showed an upregulation of ILC-like cells and eosinophils in the lungs of Mycobacterium tuberculosis infected mice upon SIRTl activation, cell subsets that were downregulated by Mycobacterium tuberculosis. Innate lymphoid cells (ILCs) have been shown to control eosinophil homeostasis, and their balance is important during infection and inflammation. Future studies are needed to understand the role of SIRTl on ILC -eosinophil crosstalk during Mycobacterium tuberculosis infection. Taken together, the data provides new insights into the plasticity/ heterogeneity of lymphoid cells during Mycobacterium tuberculosis mediated chronic inflammation and indicates the role of SIRTl activators in controlling Mycobacterium tuberculosis growth/pathogenesis by regulating myeloid cell infiltration in the lungs of Mycobacterium tuberculosis infected mice.
[0055] SIRTl activators have a favourable safety profile. Therefore, their usage as an host-directed therapies for tuberculosis could have important clinical implications through (i) avoiding the development of resistance by targeting the host and not the pathogen; (ii) shortening the course of multi-drug therapy for tuberculosis; and (iii) improving anti- Mycobacterium tuberculosis immune responses to facilitate pathogen clearance. Also as SIRTl activators modulate monocyte/macrophage subsets and chronic inflammation, they could prevent long-term pulmonary morbidity due to lung destruction in tuberculosis patients. Overall, the data provided herein demonstrates an important role for SIRTl in the Mycobacterium tuberculosis infection-associated immunopathogenesis, and suggests that activation of SIRTl can improve tuberculosis treatment outcome. Materials and Methods
[0056] Study Design. The objective of this study was to study the effect of Mycobacterium tuberculosis infection on host energy sensor viz. Sirtuins, regulating range of immuno-metabolic processes, and whether the functional connection between immune response and metabolism could be harnessed to control tuberculosis. The experiments indicated that Mycobacterium tuberculosis modulates Sirtuin 1 (SIRTl) in monocytes/macrophages and tuberculosis animal models (mice and macaque). Next, the efficacy of SIRTl activators was evaluated against Mycobacterium tuberculosis infection in mouse tuberculosis model. Also an adjunctive treatment together with isoniazid, a standard tuberculosis therapeutic drug, in mouse model was evaluated. Detailed mechanistic studies were performed to elucidate the mechanism of SIRTl activation, in controlling Mycobacterium tuberculosis growth in vitro and in mouse models (using wild type and SIRTl knock out animals). Then, a mass cytometry approach, "CyTOF", was used to characterize the landscape of pulmonary myeloid cells from Mycobacterium tuberculosis infected mice and precisely delineate the anti-inflammatory function of SIRTl. Finally, the clinical significance of Mycobacterium tuberculosis mediated SIRTl downregulation was evaluated by mining the SIRTl mRNA expression profiles from peripheral blood of active tuberculosis patients, latent tuberculosis individuals, and healthy controls from seven different cohorts.
[0057] Reagents. The following chemicals were used: SRT1720 HC1 (#A4180; Apex Bio), Resveratrol (#711004; Sigma- Aldrich), SA3 (#SC-222315; Santa Cruz), EX527 (#S 1541 ; SelleckChem) and Isoniazid (#13377; Sigma- Aldrich). The following antibodies were used: anti SIRTl (#07-131; Millipore), anti-NF-κΒ p65 (C-20 #SC-372; Santa Cruz Biotechnology Inc), anti-NF-κΒ p65 (acetyl K310) antibody (#abl9870; AbCam), anti-LC3B (#3868; Cell Signaling Technologies), anti-GAPDH (14C10) (#2118; Cell Signaling Technologies), anti-rabbit IgG, HRP-linked antibody (#7074; Cell Signaling Technologies) and mouse anti-rabbit IgG (Conformation Specific) mAb (L27A9) (#3678; Cell Signaling Technologies). Stealth SIRTl siRNAs (Set of 3: HSS 118729, HSS 177403, HSS 177404) and control siRNAs were from Life Technologies and Integrated DNA technologies respectively (#1299001).
[0058] THP-1 Cell culture. Human monocyte THP-1 cells from ATTC were maintained in Roswell Park Memorial Institute (RPMI-1640) medium (Gibco), supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1% sodium pyruvate, 1% L-glutamine, 1% nonessential amino acids (Life technologies), and 1% kanamycin (Sigma- Aldrich), at 37°C in a 5% CO2 humidified atmosphere. In infection experiments, no antibiotic was used.
[0059] Preparation of human monocyte-derived macrophages (hMDMs). Peripheral blood mononuclear cells (PBMCs) were isolated from total blood using a Ficoll gradient. Monocytes were enriched from PBMCs by CD 14 magnetic selection (Miltenyi-Biotec beads). The purified CD14+ monocytes were re-suspended in RPMI 1640 with 10% FBS, 1% penicillin, 2 mM L-glutamine, and 100 ng/ml human macrophage colony- stimulating factor (M-CSF, R&D Systems), and incubated in six-well plates at 37°C in 5% C02 for six days. The medium was changed on the fourth day. On day 6, differentiated macrophages were harvested, centrifuged, plated in fresh medium without human M-CSF, and cultured overnight. On day 7, cells were washed and used for experiments. Blood collection from healthy volunteers was approved by the Institutional Review Board (IRB), NHG Domain, Singapore.
[0060] Culture of mycobacterial strains. Mycobacterium tuberculosis (Mtb) H37Rv, HN878, CDC1551, Erdman, W148, AH30, CC13, AI10, KY strains and Mycobacterium bovis bacillus Calmette-Guerin (BCG), were grown in Middlebrook 7H9 broth (BBL Microbiology Systems), supplemented with albumin dextrose-catalase (ADC, Difco laboratories) and 0.05% Tween 80 at 37°C for 5-7 days to an optical density of 0.4-0.5 (OD600). After this time, mycobacterial cells were pelleted, re-suspended in fresh 7H9 broth with 20% glycerol, and stored at -80°C. One vial of the stock was thawed to enumerate CFU/ml. On the day of infection, the cells were thawed, washed, and sonicated prior to use. Drug-resistant strains were maintained at the Public Health Research Institute (PHRI), Newark, USA.
[0061] Infection of monocytes and macrophages with mycobacteria. Frozen Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG or M. bovis SCG-GFP or M. bovis fiCG-mCherry were thawed, washed, re-suspended in antibiotic-free RPMI-1640 with 10% FBS, and were used to infect THP-1 and hMDMs in six-well plates with a multiplicity of infection (MOI) of 5. The infected cells were incubated at 37°C with 5% C02 for 3 hours. After this time, cells were washed twice with antibiotic-free medium by centrifugation at 130 rcf. The infected cells were counted, seeded in triplicate, and either left untreated or treated with different compounds for the indicated time periods. For inhibition experiments, mycobacteria-infected cells were pre-treated with SIRT1 inhibitor EX527 for 0.5 hours before addition of SIRT1 activators. At pre-determined time points post-infection the infected cells were lysed for enumerating mycobacteria. THP-1 cells were differentiated for 16-18 hours using 4 μΜ phorbol myristate acetate (PMA, Sigma) prior to infection with multi-drug resistant (MDR) strains of Mycobacterium tuberculosis.
[0062] Cell viability. PrestoBlue™ Cell Viability Reagent (Invitrogen) was used to assess the cell viability of THP-1 cells upon addition of resveratrol or SRT1720 at varying concentrations over 72 hours. 20 μΐ^ was added to each well and incubated for 20 minutes at 37 °C, and fluorescence was read on a plate reader excited at 560 nm with non-conjugated light emissions collected at 590 nm.
[0063] NAD+ to NADH ratio measurement. Quantification of NAD+ and NADH was carried out using the NAD+/NADH assay kit (Abeam #ab65348), according to the manufacturer's instructions. NAD+ and NADH values were normalized by protein concentration.
[0064] Transfection of siRNAs. To knock down SIRT1 expression, THP-1 cells were transfected with siRNAs using the Lipofectamine 2000 kit (Invitrogen), according to the manufacturer's protocol. Knockdown of SIRT1 was confirmed by western blotting. All transfection data is the mean + SEM of three independent experiments, performed in duplicate.
[0065] Western blot. Protein lysates from Mycobacterium tuberculosis infected THP-1 cells, either untreated or treated with Sirtuin 1 activators, were obtained by lysis in RIPA buffer (Sigma) with protease (Roche) and phosphatase (Roche) inhibitors at indicated time points. A Micro BCA Protein Kit (Thermo Scientific) was used to measure protein levels, and equal amounts of proteins were resolved by electrophoresis on 12% Tris-HCL gels (Mini- PROTEAN TGX gels, Bio-Rad) and transferred onto PVDF membranes (Trans-blot Turbo transfer pack, BioRad). Membranes were developed using the indicated primary antibody at a 1: 1000 dilution, and secondary antibodies at a 1:3000 dilution in blocking solution. This was followed by incubation in chemiluminescent horseradish peroxidase (HRP) detection reagent (Millipore) for 1 minute prior to image acquisition.
[0066] Chromatin immunoprecipation (ChIP) assay. ChIP assays were performed with samples from uninfected and Mycobacterium tuberculosis infected THP-1 cells, treated or untreated with SRT1720, using the anti- Fi B p65 antibody (C-20, Santa Cruz Biotechnology Inc) or normal rabbit IgG, with the SimpleChIP Plus Enzymatic Chromatin IP Kit (Cell Signaling Technologies), following the standard protocol. DNA fragments were subjected to qRT-PCR using primers flanking NF-κΒ response elements on various targets. ChIP qRT-PCR data analysis was performed.
[0067] Measurement of M. bovis BCG in lysosomes. THP-1 cells were infected with GFP-conjugated BCG. After infection, cells were incubated with 500 nM LysoTracker (LTR; Invitrogen) in the presence or absence of drugs for 4 or 24 hours. Cells were then washed with PBS and fixed in 4 % paraformaldehyde for 20 minutes at room temperature. Fixed cells were then washed with phosphate-buffered saline (PBS). Fluorescence intensities of GFP- BCG and LTR were analysed using an Olympus FV1000 confocal microscope and used to calculate the number of bacteria co-localized with LTR together with the total number of intracellular bacteria. In total, at least 200 infected cells were counted for different analyses.
[0068] Autophagy analysis. Anti-LC3 antibody from Cell Signaling Technologies was used for flow cytometric analysis and for Western blotting at a dilution of 1:250 and 1: 1000, respectively. See Supplemental Experimental Procedures for details on Mass Cytometry and Flow cytometry. As a positive control, cells were treated with 200 nM Rapamycin or ΙμΜ isoniazid (INH) for 4 hours.
[0069] Mouse models of infection with Mycobacterium tuberculosis . The in vivo anti- tubercular activity of SRT1720 and resveratrol (RES) was evaluated in an acute and chronic infection model of C57BL/6 mice. Female C57BL/6 mice (6-8 weeks old) were infected with Mycobacterium tuberculosis H37Rv using the nose-only aerosolization system (CH Technologies). Three to four animals were sacrificed on day 1 to determine the number of bacteria implanted in the lungs. Seven days after infection, animals were randomly distributed into different groups prior to the start of treatment in the acute model. In the chronic model, treatment was started at day 40 post-infection. Treatment with the indicated drugs was administered by gavage once a day, six days a week. Mice were sacrificed at predetermined time points (two or four weeks after initiation of treatment), followed by harvesting of tissues and enumeration of Mycobacterium tuberculosis colony forming units (CFU). A total of six experiments, five acute and one chronic, were performed, where SRT1720 or resveratrol were administered in combination with isoniazid. All mice were housed in a biosafety level 3 (BSL3) laboratory, and treated humanely using procedures described in animal care protocols. The myeloid cell-specific SIRTl KO (Mac-SIRTl KO) mice were a gift from Xiaoling Li (National Institute of Environmental Health Sciences). The mouse model was generated from mice expressing a conditional SIRT1 floxed allele bred into a C57/BL6 background, and then crossed with mice expressing Cre recombinase under a myeloid- specific cell promoter. Mac-SIRTl KO mice were housed in a biosafety level 3 (BSL3) laboratory at the University of Massachusetts Medical School (UMMS), USA, and treated humanely using procedures described in animal care protocols.
[0070] Enumeration of Mycobacterium tuberculosis CFU in infected mice. The mycobacterial load in the lung and spleen of infected mice was quantified by plating tissue homogenates on Middlebrook 7H11 agar supplemented with oleic albumin dextrose catalase (OADC). At pre-determined time points post-infection/post-treatment, mice were euthanized, and lungs and spleen were aseptically excised, washed in PBS, and homogenized in PBS containing 0.25% Tween 80 using a MACS tissue dissociator (Miltenyi Biotech). A series of dilutions of tissue homogenate were plated on Middlebrook 7H11 agar in triplicate. Agar plates were incubated at 37°C for three weeks, after which colonies were counted visually. CFU obtained from two or three dilutions were used to calculate the total number of CFU/tissue/mouse.
[0071] CyTOF marker labelling, flow cytometry, data acquisition and analysis. Lung cells were stained with heavy-metal isotope-labelled antibodies (Table 6) , barcoded and were acquired on CyTOF 1 (Fluidigm). Samples were de-barcoded using manual gating in FlowJo and analysis of live CD45+CD3-CD90-CD19- myeloid cells was carried out using the t- distributed stochastic neighbour embedding (tSNE) dimension reduction and DensVM density-based clustering algorithm. Flow cytometry was performed to validate CyTOF data (in independent experiment) and to assess the infiltration of myeloid cells in Mycobacterium tuberculosis infected Mac-SIRTl KO mice.
[0072] Histology and Morphometry. The upper right lobes of mouse lungs were fixed in 10% buffered formalin and paraffin-embedded. Sections were stained with Hematoxylin- Eosin (H&E) or Ziehl-Neelsen (ZN) acid-fast stain for evaluation of pathology and photography. Stained sections were photographed in a Nikon Microphot-FX photomicrographic system with NIS-Elements F3.0 software (Nikon Instruments Inc.). Morphometric analysis of lung involvement in pathology was performed using PathScan Enabler IV slide scanner (Meyer Instruments) and SigmaScan Pro 5 (SPSS Scence Inc.) a computer-based image analysis system. Morphometry of the lesions was performed also using SigmaScan Pro 5. A calibration micrometre slide was used to determine the area evaluated. The system allows performing the analysis at significantly higher magnification and resolution on digital images. The area of all lesions in a section was measured first and then the percentage from the area of the whole section was calculated (lung involvement).
[0073] Immunohistochemistry of Macaque lung sections. Slides (5-μιη thick) were cut from formalin-fixed, paraffin-embedded tissue blocks, subjected to double antigen retrieval, and stained with SIRT1 antibody (E104, AbCam, 1: 150), CD3, CD68 and CD163. Detection was performed with an anti-rabbit Mach 3 Rabbit AP Polymer Kit (Biocare), and slides were counterstained with YO-PRO nuclei stain (Molecular Probes). The images were taken on a CRi Microscope, and counted using InForm software. Images were processed using Adobe Photoshop. Only those cells that exhibited a SIRT1 signal at least 15 arbitrary units bright from each nuclei were considered positive and included for quantification.
[0074] Real-time RT-qPCR. THP-1 cells or mouse lung cells were lysed and homogenized in TRIZOL reagent (Invitrogen), and total RNA was isolated using the RNeasy Mini Kit (Qiagen). RNA was reverse transcribed using the iScript cDNA synthesis kit (Bio- Rad). cDNA was used for real-time qPCR using 2x iQ SYBR Green Supermix and an iCycler (Bio-Rad). The primers for real-time RT-qPCR are described in Table 7. The mRNA expression levels in infected cells/tissue were normalized to GAPDH expression, and fold induction was calculated by the AACT method relative to those in uninfected cells/tissue. RT- qPCR was performed in triplicate.
[0075] Microarray analysis. Mycobacterium tuberculosis infected THP-1 cells, treated or untreated with 100 μΜ of resveratrol for 24 hours (three biological replicates for each condition), were harvested and homogenized in mirVana lysis buffer (Life Technologies). RNA was extracted using the mirVana miRNA Isolation Kit (Life Technologies). Uninfected cells were kept as controls. RNA quality was confirmed using the Agilent Bioanalyzer and only samples with RNA Integrity Number >7 were processed. Biotinylated cRNA was prepared from 100 ng of total RNA using the Epicentre TargetAmp Nano-g Biotin-aRNA labeling kit for the Illumina system, followed by hybridization on Illumina human arrays. Raw expression data was extracted using GenomeStudio Gene Expression v 1.9.0, and processed with quantile normalization. Hierarchical clustering analysis with complete linkage algorithms was performed using R. Heat maps were plotted using SpotFire (TIBCO Software Inc. http://spotfire.tibco.com ). Differential expression analysis was performed using Linear Models for Microarray Data (LIMMA). GO analysis was carried out by DAVID. Pathway analysis was carried out using IPA (Ingenuity® Systems, www.ingenuity.com).
[0076] Gene expression analysis of Macaque granulomas. Granuloma samples were collected from animals infected with a moderate dose of Mycobacterium tuberculosis CDC1551 (50-100 cfu) via aerosol, which resulted in the development of either active tuberculosis or latent tuberculosis infection. These samples were used for isolation of total RNA and subjected to host transcriptomics using Agilent Rhesus Macaque specific microarrays (Agilent, Palo Alto, CA), relative to normal lung tissue derived from uninfected macaques as baseline as described earlier. As described earlier, control lung samples were labelled with Cy3 while lesion samples were labelled with Cy5 and co-hybridized on arrays. Data was normalized using locally weighted scatterplot smoothing and data specific for SIRT1 was analysed across the matrix and hierarchically clustered using Spotfire DecisionSite for Microarray Analysis (http://spotfire.tibco.com/).
[0077] Cytokine analysis. ELISAs for IL-Ιβ, JL6, and MCP-1 were performed on THP-1 cell culture supernatants using human cytokine/chemokine- specific ELISA kits (eBiosciences, BioLegend) as per manufacturers' instructions. In vitro cell culture experiments were carried out in triplicate, a minimum of three times. Lung homogenates from three or four mice in each group were assayed by Luminex 100, using Exponent 3.2 software and Milliplex™ MAP for Luminex xMAP Technology Assay (MCYTOMAG-70K mouse cytokine 32-plex; Millipore). The standard concentrations ranged from 3.2 to 10,000 pg/ml.
[0078] Human cohorts. SIRT1 gene expression profiles were retrieved from Gene Expression Omnibus. Eight publicly available clinical datasets of whole blood gene expression profiles from active tuberculosis patients (n = 201), individuals with latent tuberculosis (n = 191), healthy controls (n = 18), patients with tuberculosis undergoing therapy at various time points (n = 38) and patients with other diseases (n = 110) were analysed (Table 2).
[0079] Statistics. All values are expressed as the mean ± SEM of individual samples. Samples were analysed using Student's t-test and Mann-Whitney test for two groups and ANOVA for multiple groups. Human expression data was analysed using Mann-Whitney between patient groups within each dataset. Dataset of individual active tuberculosis patients undergoing treatment over time was analysed using a paired Wilcoxon signed-rank test. [0080] Accession Codes. GEO accession of microarray data is GSE78233.
[0081] Study Approval. The study was approved by the Institutional Biosafety Committee (IBC) and Institutional Animal Care and Use Committee (IACUC) of the Biological Resource Council (BRC), A*STAR, Singapore and the University of Massachusetts Medical School (UMMS), USA.
TABLES
[0082] Table 1. SRT1720 treatment enhances efficacy of isoniazid in Mycobacterium tuberculosis infected mice.
Lungs Spleen
Mouse model
INH1 SRT+INIP INH SRT+INH
Acute
Expt 1 11
2/4 (50%) 4/5 (80%) 4/5 (80%) 5/5 (100%)
Expt 2 1/4 (25%) 1/4 (25%) 0/5 (0%) 5/5 (100%)
Chronic 10.7+2.5 x 10' 4.9+2.8 x 104 NP NP
Definition of abbreviations: INH= isoniazid; SRT= SRT1720; NP = not performed.
*In an acute tuberculosis model proportion of mice with no detectable CFUs in the lungs and spleen during INH therapy with and without SRT1720, after 4 weeks of treatment in two different experiments.
n a chronic tuberculosis model bacterial load (CFU) in the lung of INH or SRT+INH treated mice after 2 weeks of treatment.
* Mycobacterium tuberculosis infected mice were administered 10 mg/kg of INH.
"Number of mice with no detectable CFU out of total number of animals in that group. In bracket percentage information is provided.
**Mean CFU values (n = 5). Difference in CFU values between INH and SRT+INH group is significant. P < 0.05 by Mann- Whitney test.
§Mtb-infected mice were co-administered with INH and 100 mg/kg of SRT.
[0083] Table 2. Tuberculosis datasets used in this study.
Country jjeaimy Active ^°St Latent Other Study Microarra GEO
ID or . · treatment ,. rereren , ,t
. controls TB . TB diseases - T y platrorm accession cohort active ce No. r TB
Illumina
United
UK Human
kingdo 12 21 21 18 GSE 19444 '10 HT-12
m
v3.0
Illumina
SA' South Human
20 31 18 GSE 19442 10 Africa HT-12
v3.0
Illumina
SA South Human
21 23 22 GSE50834 '14 Africa HT-12
v4.0
Illumina
SA South Human
29 29 38 19 GSE40553 '12 Africa HT-12
v4.0
Affymetri
x Human
Chin Genome
China 21 GSE54992 a ' 14 U133 Plus
2.0 Array
Affymetri
x Human
Viet Vietna Genome
20 GSE11199 '08 m U133 Plus
2.0 Array
Illumina
SA Human
Malawi 97 97 83 23 GSE37250 '13 HT-12
V4.0
[0084] Table 3. Differentially expressed genes between Mycobacterium tuberculosis infected THP-1 cells treated with resveratrol (RES) vs untreated cells. Corresponding log fold changes of Infected vs Uninfected cells are also shown.
Infected+
Infected vs Infected+
Infected vs RES vs
S. Uninfected RES vs
Probe Gene ID Gene symbol Uninfected Infected
No. (log fold Infected
(P value) (log fold
change) (P value) change)
1 ILMN_ .1651346 353376 TICAM2 1.102 1.87E-14 -0.245 2.38E-03
2 ILMN_ .1652003 2790 GNG10 0.490 5.28E-05 -0.570 4.24E-06
3 ILMN_ .1652065 3779 KCNMB1 0.541 6.25E-08 -0.585 1.13E-08
4 ILMN_ .1652085 10199 MPHOSPH10 0.278 6.12E-03 -0.329 4.67E-04
5 ILMN_ .1652185 3566 IL4R 1.870 9.20E-21 -0.663 1.25E-09 ILMN_ .1652219 140688 C20orfl l2 0.328 4.39E-03 -0.387 9.43E-04
ILMN_ .1652413 90226 UCN2 0.374 1.18E-04 -0.256 5.30E-03
ILMN_ .1652417 389760 DC36 0.253 8.01E-03 -0.474 1.59E-06
ILMN_ .1652649 643722 LOC643722 0.232 1.05E-02 -0.243 7.60E-03
ILMN_ .1652680 652616 LOC652616 2.274 7.15E-19 -0.820 3.89E-10
ILMN_ .1652787 118788 PIK3AP1 1.767 4.68E-17 -0.413 1.16E-04
ILMN_ .1652825 3587 IL10RA 3.629 1.59E-28 -1.181 1.49E-15
ILMN_ .1653180 7171 TPM4 0.838 2.54E-10 -1.211 4.42E-14
ILMN_ .1653283 351 APP 0.293 2.93E-03 -0.261 7.57E-03
ILMN_ .1653591 135644 TRIM40 0.284 4.98E-03 -0.333 1.03E-03
ILMN_ .1653601 646144 LOC646144 0.405 5.72E-05 -0.231 8.61E-03
ILMN_ .1653652 5788 PTPRC 0.749 7.88E-10 -0.499 1.06E-06
ILMN_ .1654010 56894 AGPAT3 0.375 2.45E-04 -0.660 2.67E-08
ILMN_ .1654318 25930 PTPN23 0.281 7.93E-04 -0.213 5.08E-03
ILMN_ .1654319 145864 HAPLN3 1.322 1.65E-14 -0.784 1.75E-09
ILMN_ .1654331 3214 HOXB4 0.277 8.51E-03 -0.283 2.76E-03
ILMN_ .1654340 7360 UGP2 0.616 2.81E-07 -0.379 1.02E-04
ILMN_ .1654389 728744 LOC728744 1.263 2.54E-14 -0.358 3.85E-04
ILMN_ .1654398 23179 RGL1 4.731 5.72E-29 -1.212 4.75E-15
ILMN_ .1654436 90987 ZNF251 0.493 2.71E-04 -0.620 2.14E-06
ILMN_ .1654488 7403 UTX 0.820 4.29E-10 -0.405 7.15E-05
ILMN_ .1654560 10333 TLR6 2.189 1.06E-19 -0.534 1.21E-06
ILMN_ .1654630 54540 FAM193B 0.256 6.71E-03 -0.239 3.40E-03
ILMN_ .1654685 79772 MCTP1 1.226 1.15E-14 -0.297 1.30E-03
ILMN_ .1654690 27440 CECR5 0.356 1.27E-04 -0.501 1.30E-06
ILMN_ .1654773 8573 CASK 1.332 7.07E-17 -0.721 2.19E-10
ILMN_ .1655077 639 PRDM1 2.520 1.58E-22 -0.313 7.73E-04
ILMN_ .1655572 79992 C6orf59 1.025 3.07E-11 -0.483 3.29E-06
ILMN_ .1655644 91752 ZNF804A 0.714 6.02E-11 -0.208 7.34E-03
ILMN_ .1655766 340120 ANKRD34B 0.638 9.31E-07 -0.562 7.03E-07
ILMN_ .1655821 822 CAPG 0.725 9.00E-09 -0.778 2.59E-09
ILMN_ .1655864 653853 LOC653853 0.249 5.54E-03 -0.318 3.40E-04
ILMN_ .1655884 488 ATP2A2 0.465 1.05E-06 -0.606 1.10E-08
ILMN_ .1655935 113 ADCY7 0.704 1.25E-09 -0.416 1.67E-05
ILMN_ .1656011 5996 RGS1 5.380 7.08E-27 -3.387 7.35E-22
ILMN_ .1656254 388677 NOTCH2NL 0.638 1.44E-08 -0.477 3.40E-06
ILMN_ .1656361 201175 LOC201175 0.478 4.56E-05 -0.564 3.83E-07
ILMN_ .1656386 9871 SEC24D 0.764 3.00E-10 -0.279 1.69E-03
ILMN_ .1656670 3135 HLA-G 1.875 1.64E-20 -0.261 1.91E-03
ILMN_ .1656938 731486 LOC731486 1.980 2.11E-20 -0.824 1.09E-11
ILMN_ .1657423 51324 SPG21 1.038 1.22E-14 -0.672 4.35E-10
ILMN_ .1657435 4499 MT1M 0.994 4.68E-12 -0.519 2.09E-06
ILMN_ .1657550 4597 MVD 0.468 4.34E-05 -0.459 1.91E-06
ILMN_ .1657708 11343 MGLL 1.737 9.17E-19 -0.336 1.72E-04 ILMN_ .1657836 64857 PLEKHG2 0.567 2.09E-08 -0.354 6.29E-05
ILMN_ .1657871 91543 RSAD2 4.331 2.95E-28 -0.354 4.51E-04
ILMN_ .1657892 51311 TLR8 2.745 3.63E-25 -1.938 2.56E-21
ILMN_ .1658028 732371 LOC732371 0.673 1.56E-08 -0.522 8.09E-07
ILMN_ .1658337 79647 AKIRIN1 0.441 2.87E-06 -0.251 2.04E-03
ILMN_ .1658416 51023 MRPS18C 0.442 4.98E-06 -0.258 3.06E-03
ILMN_ .1658472 51107 APH1A 0.239 7.86E-03 -0.378 8.47E-05
ILMN_ .1658483 3552 ILIA 1.114 1.97E-13 -0.404 4.09E-05
ILMN_ .1658494 28984 C13orfl5 2.548 4.60E-23 -0.777 2.50E-10
ILMN_ .1658513 23096 IQSEC2 0.459 3.69E-05 -0.316 2.40E-03
ILMN_ .1658709 3912 LAMB1 0.859 9.68E-11 -0.369 8.20E-05
ILMN_ .1658962 3937 LCP2 0.765 1.05E-10 -0.563 6.73E-08
ILMN_ .1658995 23597 ACOT9 1.649 1.37E-17 -0.858 5.52E-11
ILMN_ .1659255 6102 RP2 0.475 1.23E-04 -0.312 5.66E-03
ILMN_ .1659688 3959 LGALS3BP 2.710 1.21E-23 -0.399 1.90E-05
ILMN_ .1659752 730996 LOC730996 0.752 7.77E-10 -0.351 9.49E-05
ILMN_ .1659766 9531 BAG3 0.721 4.88E-11 -0.379 1.20E-05
ILMN_ .1659960 259307 IL4I1 5.876 3.24E-33 -0.219 7.24E-03
ILMN_ .1659976 10978 CLP1 0.430 1.87E-06 -0.329 1.25E-04
ILMN_ .1659984 4224 MEP1A 0.327 1.28E-04 -0.362 4.75E-05
ILMN_ .1660027 2213 FCGR2B 0.857 2.99E-12 -0.627 2.60E-09
ILMN_ .1660031 5031 P2RY6 1.080 1.15E-11 -1.093 2.24E-12
ILMN_ .1660436 3304 HSPA1B 1.185 2.44E-14 -0.405 4.32E-05
ILMN_ .1660462 255231 MCOLN2 0.273 8.05E-04 -0.243 3.05E-03
ILMN_ .1660624 3985 LIMK2 0.474 9.07E-08 -0.630 5.96E-10
ILMN_ .1660844 92105 INTS4 0.233 2.83E-03 -0.255 1.71E-03
ILMN_ .1660871 10783 NEK6 1.175 1.52E-15 -0.775 5.00E-11
ILMN_ .1660923 54435 HCG4 2.087 2.56E-22 -0.295 3.72E-04
ILMN_ .1661173 9325 TRIP4 1.140 1.32E-14 -0.404 1.13E-05
ILMN_ .1661293 7767 ZNF224 0.481 7.14E-07 -0.252 2.25E-03
ILMN_ .1661366 5223 PGAM1 0.240 4.63E-03 -1.002 4.50E-13
ILMN_ .1661439 10211 FLOT1 1.678 1.40E-17 -0.586 1.55E-07
ILMN_ .1661695 11213 IRAK3 0.227 2.86E-03 -0.202 8.36E-03
ILMN_ .1661755 64855 FAM129B 1.623 1.22E-18 -0.698 4.43E-10
ILMN_ .1661895 51050 PI15 0.553 2.07E-06 -0.588 7.76E-07
ILMN_ .1662026 695 BTK 0.585 4.93E-09 -0.455 5.90E-07
ILMN_ .1662316 65082 VPS33A 0.250 5.78E-03 -0.428 8.94E-06
ILMN_ .1662358 4599 MX1 2.684 3.18E-25 -0.258 1.40E-03
ILMN_ .1662451 2208 FCER2 0.537 1.79E-06 -0.653 6.71E-08
ILMN_ .1662686 10208 USPL1 0.658 2.42E-10 -0.427 1.08E-06
ILMN_ .1662799 63940 GPSM3 0.251 1.54E-03 -0.344 3.51E-05
ILMN_ .1662848 79770 TXNDC15 0.287 9.61E-03 -0.332 1.94E-03
ILMN_ .1663090 6651 SON 0.228 6.19E-03 -0.460 1.33E-06
ILMN_ .1663347 9381 OTOF 1.184 9.89E-13 -0.830 2.05E-09 ILMN_ .1663618 6774 STAT3 0.875 2.70E-12 -0.561 3.10E-08
ILMN_ .1663866 7045 TGFBI 1.112 2.47E-14 -0.580 4.53E-08
ILMN_ .1663873 4322 MMP13 0.492 6.77E-05 -0.437 1.36E-04
ILMN_ .1664362 84251 SGIP1 2.129 1.95E-22 -1.579 6.94E-19
ILMN_ 1664449 29880 ALG5 0.255 7.27E-03 -0.410 8.09E-05
ILMN_ 1664464 5730 PTGDS 0.328 1.38E-03 -0.265 8.02E-03
ILMN_ .1664631 10863 ADAM28 0.876 5.40E-12 -0.493 5.71E-07
ILMN_ .1664691 27071 DAPP1 1.161 1.01E-12 -0.272 4.46E-03
ILMN_ .1664761 51524 TMEM138 1.182 5.42E-16 -0.628 1.46E-09
ILMN_ .1664802 26118 WSB1 0.969 1.48E-10 -0.434 6.47E-05
ILMN_ .1664828 164668 APOBEC3H 1.989 7.72E-21 -0.483 1.19E-06
ILMN_ .1664833 54534 MRPL50 0.188 1.04E-02 -0.319 8.08E-05
ILMN_ .1664920 83636 C19orfl2 0.729 2.79E-10 -0.486 6.57E-07
ILMN_ .1664931 2961 GTF2E2 0.828 6.56E-13 -0.198 7.61E-03
ILMN_ .1665135 5930 RBBP6 0.402 1.55E-05 -0.309 4.31E-04
ILMN_ .1665455 123879 DCUN1D3 1.021 5.23E-13 -0.334 2.61E-04
ILMN_ .1665682 3601 IL15RA 2.580 2.10E-25 -0.605 1.61E-09
ILMN_ .1665865 3487 IGFBP4 1.634 5.71E-18 -0.272 2.25E-03
ILMN_ .1665871 23357 ANGEL 1 1.009 6.53E-13 -0.228 8.86E-03
ILMN_ .1666089 116448 OLIG1 0.627 4.13E-08 -1.129 1.14E-13
ILMN_ .1666269 1522 CTSZ 0.972 1.90E-12 -0.917 8.71E-12
ILMN_ .1666376 81844 TRIM56 1.194 6.15E-15 -0.220 7.66E-03
ILMN_ 1666444 5937 RBMS1 0.729 1.20E-09 -0.233 8.67E-03
ILMN_ .1667224 56833 SLAMF8 4.558 3.38E-29 -1.414 2.52E-16
ILMN_ .1667430 8560 DEGS1 0.421 3.41E-05 -0.267 3.95E-03
ILMN_ .1667476 4055 LTBR 0.704 1.89E-10 -0.694 4.44E-10
ILMN_ .1667748 341405 ANKRD33 2.430 1.21E-23 -0.684 4.99E-10
ILMN_ .1667825 197259 MLKL 1.158 3.30E-16 -0.720 3.48E-11
ILMN_ .1667893 64759 TNS3 1.519 7.28E-18 -0.807 2.40E-11
ILMN_ .1668039 2995 GYPC 1.050 2.51E-14 -0.945 1.90E-13
ILMN_ .1668442 54072 C21orf42 0.593 1.15E-06 -0.347 6.06E-04
ILMN_ .1668514 23396 PIP5K1C 0.592 5.55E-08 -0.518 6.34E-07
ILMN_ .1668743 728069 LOC728069 0.748 2.66E-10 -0.303 5.36E-04
ILMN_ .1668748 51586 MED 15 0.275 3.29E-03 -0.222 8.97E-03
ILMN_ .1668822 10538 BATF 0.336 5.20E-05 -0.799 1.03E-11
ILMN_ .1668979 79982 DNAJB14 0.524 3.59E-06 -0.299 5.35E-04
ILMN_ .1669252 8453 CUL2 0.615 2.86E-09 -0.446 9.61E-07
ILMN_ .1669376 55332 DRAM1 3.563 4.17E-28 -0.549 6.27E-08
ILMN_ .1669714 4625 MYH7 0.361 5.55E-04 -0.392 1.51E-04
ILMN_ .1669781 5618 PRLR 0.427 1.82E-05 -0.538 6.54E-07
ILMN_ .1669982 114800 CCDC85A 1.775 4.73E-18 -0.736 2.44E-09
ILMN_ .1670124 150223 LOCI 50223 0.708 2.98E-09 -0.615 1.74E-08
ILMN_ .1670272 26020 LRP10 1.082 1.17E-14 -0.401 4.75E-06
ILMN_ .1670305 710 SERPWG1 2.806 1.13E-22 -1.798 2.53E-18 ILMN_ .1670379 84168 ANTXR1 0.529 6.23E-07 -0.620 4.38E-08
ILMN_ .1670490 10630 PDPN 1.918 3.61E-16 -1.590 4.32E-15
ILMN_ .1670609 475 ATOX1 1.207 3.52E-16 -0.278 6.01E-04
ILMN_ .1670638 26207 PITPNC1 0.680 3.51E-09 -0.652 9.06E-09
ILMN_ .1670926 51363 CHST15 1.196 4.12E-12 -0.948 4.84E-10
ILMN_ .1671067 9969 MED 13 0.750 8.78E-09 -0.401 1.14E-04
ILMN_ .1671142 8111 GPR68 0.417 5.09E-05 -0.960 1.18E-11
ILMN_ .1671154 84000 TMPRSS13 0.495 3.71E-05 -0.307 2.07E-03
ILMN_ .1671452 65080 MRPL44 0.236 8.71E-03 -0.616 4.11E-08
ILMN_ .1671482 130589 GALM 1.998 3.25E-19 -1.152 4.22E-14
ILMN_ .1671885 8079 MLF2 0.472 1.49E-05 -0.379 2.38E-05
ILMN_ .1672006 6741 SSB 0.924 1.33E-12 -0.323 2.32E-04
ILMN_ .1672295 80149 ZC3H12A 3.397 5.64E-26 -0.828 7.91E-11
ILMN_ .1672496 3301 DNAJA1 0.520 1.83E-08 -0.272 5.08E-04
ILMN_ .1672547 4650 MY09B 0.520 5.00E-08 -0.323 1.19E-04
ILMN_ .1672582 653220 X AGE IB 0.936 1.74E-12 -0.371 6.94E-05
ILMN_ .1672589 10509 SEMA4B 0.496 4.35E-05 -0.589 8.78E-07
ILMN_ .1672878 29 ABR 0.846 1.38E-12 -0.235 2.83E-03
ILMN_ .1673030 1240 CMKLR1 0.603 9.23E-08 -0.555 5.05E-07
ILMN_ .1673409 84848 MGC16121 0.660 2.27E-07 -0.440 4.69E-05
ILMN_ .1673586 6533 SLC6A6 1.165 2.88E-13 -0.410 1.67E-05
ILMN_ .1673649 10525 HYOU1 0.434 5.96E-06 -0.524 2.91E-07
ILMN_ .1673711 3326 HSP90AB 1 0.210 5.60E-03 -0.647 7.79E-10
ILMN_ .1673788 55573 CDV3 0.314 1.49E-03 -0.495 4.20E-06
ILMN_ .1673917 2969 GTF2I 0.852 1.33E-10 -0.632 2.09E-08
ILMN_ .1673953 3269 HRH1 1.233 2.48E-15 -0.261 2.00E-03
ILMN_ .1674038 1509 CTSD 2.019 9.82E-19 -0.806 2.11E-09
ILMN_ .1674160 274 BIN1 0.888 1.60E-11 -0.584 6.50E-08
ILMN_ .1674282 5467 PPARD 1.143 7.89E-14 -0.350 1.84E-04
ILMN_ .1674285 401233 LOC401233 1.451 1.64E-16 -0.564 2.16E-07
ILMN_ .1674563 6351 CCL4 1.330 9.45E-14 -0.594 3.12E-07
ILMN_ .1674593 114132 SIGLECl l 0.661 4.55E-08 -0.299 2.18E-03
ILMN_ .1674719 4811 NIDI 0.455 2.67E-06 -0.571 3.03E-08
ILMN_ .1674985 55092 TMEM51 1.790 3.75E-20 -0.448 1.54E-06
ILMN_ .1675130 4782 NFIC 0.327 7.08E-03 -0.439 9.18E-05
ILMN_ .1675156 998 CDC42 0.412 2.23E-05 -0.690 1.67E-09
ILMN_ .1675192 3452 IFNA21 0.664 1.31E-05 -0.307 2.11E-03
ILMN_ .1675448 677 ZFP36L1 3.056 2.63E-21 -1.859 2.51E-17
ILMN_ .1675507 11217 AKAP2 0.470 2.37E-06 -0.345 1.35E-04
ILMN_ .1675671 23308 ICOSLG 1.091 5.36E-15 -0.256 1.64E-03
ILMN_ .1675848 10627 MYL12A 0.598 1.26E-09 -0.213 4.33E-03
ILMN_ .1676213 27286 SRPX2 0.430 6.52E-06 -0.238 5.53E-03
ILMN_ .1676372 30835 CD209 2.249 7.24E-21 -1.884 6.48E-19
ILMN_ .1676413 7447 VSNL1 1.019 1.72E-13 -0.589 3.15E-08 ILMN_ 1676448 57590 WDFY1 0.538 1.14E-07 -0.446 2.64E-06
ILMN_ .1676893 109 ADCY3 0.287 8.82E-04 -0.472 7.79E-07
ILMN_ .1676899 55689 YEATS2 1.006 2.60E-14 -0.428 2.33E-06
ILMN_ .1677178 245934 DEFB121 0.304 1.16E-02 -0.319 6.97E-03
ILMN_ .1677308 83872 HMCN1 0.623 9.47E-09 -0.574 3.79E-08
ILMN_ .1677567 1833 EPYC 1.079 5.67E-14 -1.091 3.56E-14
ILMN_ .1677827 51284 TLR7 1.427 7.18E-17 -0.380 3.67E-05
ILMN_ .1677843 53917 RAB24 0.960 9.87E-13 -0.217 4.72E-03
ILMN_ .1678422 79132 DHX58 2.838 5.51E-25 -0.362 1.72E-05
ILMN_ .1678437 10129 FRY 0.432 3.50E-06 -0.704 5.90E-10
ILMN_ .1678579 1376 CPT2 0.218 6.07E-03 -0.221 6.00E-03
ILMN_ .1678745 84955 NUDCD1 0.358 4.02E-04 -0.435 4.38E-05
ILMN_ .1678833 1230 CCR1 1.909 6.50E-19 -0.856 l.OlE-10
ILMN_ .1678922 26091 HERC4 0.520 7.59E-08 -0.269 9.41E-04
ILMN_ .1679133 1992 SERPWB l 1.168 5.82E-16 -0.358 2.55E-05
ILMN_ .1679217 90362 FAM110B 1.190 1.81E-14 -0.298 5.21E-04
ILMN_ .1679268 57162 PELI1 2.235 5.62E-23 -0.348 6.29E-05
ILMN_ .1679299 3547 IGSF1 1.319 1.54E-17 -0.725 4.25E-11
ILMN_ .1679339 375341 C3orf62 0.636 1.51E-07 -0.790 1.55E-10
ILMN_ .1679693 84910 TMEM87B 0.880 2.35E-10 -0.533 3.02E-07
ILMN_ .1679929 51621 KLF13 0.934 1.34E-13 -0.758 2.48E-11
ILMN_ .1680109 10087 COL4A3BP 0.654 2.53E-09 -0.436 1.41E-06
ILMN_ .1680139 23764 MAFF 1.564 6.74E-16 -0.279 2.72E-03
ILMN_ .1680192 200315 APOBEC3A 1.377 7.35E-17 -0.581 3.34E-08
ILMN_ .1680339 5157 PDGFRL 3.813 4.40E-28 -0.347 1.80E-04
ILMN_ .1680390 2651 GCNT2 1.136 1.08E-13 -0.472 1.56E-06
ILMN_ .1680419 140460 ASB7 0.576 2.32E-07 -0.227 6.48E-03
ILMN_ .1680465 221079 ARL5B 1.353 6.42E-16 -0.228 7.43E-03
ILMN_ .1680644 54468 MIOS 0.521 1.30E-07 -0.363 3.11E-05
ILMN_ .1680782 219988 PATL1 1.278 9.75E-16 -0.242 4.39E-03
ILMN_ .1680831 9031 BAZ1B 0.416 1.22E-05 -0.386 4.57E-05
ILMN_ .1680937 8347 HIST1H2BC 0.480 5.52E-06 -0.442 4.11E-06
ILMN_ .1680973 2294 FOXF1 0.684 8.12E-09 -0.338 3.32E-04
ILMN_ .1681067 23533 PIK3R5 0.535 6.11E-07 -0.333 4.31E-04
ILMN_ .1681203 5756 TWF1 0.541 1.23E-06 -0.453 1.01E-05
ILMN_ .1681301 9447 AIM2 3.115 1.70E-23 -0.877 1.16E-11
ILMN_ .1681628 11179 ZNF277 1.249 5.67E-16 -0.323 2.29E-04
ILMN_ .1681855 4943 TBC1D25 0.361 2.31E-03 -0.402 9.52E-05
ILMN_ .1682054 6717 SRI 0.301 2.07E-03 -0.373 2.40E-04
ILMN_ .1682081 127544 RNF19B 2.645 8.51E-25 -0.607 5.38E-09
ILMN_ .1682312 1536 CYBB 2.819 1.60E-21 -1.115 1.46E-11
ILMN_ .1682717 8870 IER3 3.473 9.50E-23 -0.320 8.34E-03
ILMN_ .1682761 388325 C17orf87 1.261 7.29E-13 -0.561 4.56E-06
ILMN_ .1682937 284654 RSPOl 0.466 3.71E-06 -0.333 3.71E-04 ILMN_ .1682993 4818 NKG7 0.934 8.71E-13 -0.881 1.96E-12
ILMN_ .1683178 3717 JAK2 1.147 6.44E-15 -0.321 2.20E-04
ILMN_ .1683250 440731 LOC440731 0.320 5.30E-04 -0.334 2.73E-04
ILMN_ .1683415 817 CAMK2D 0.596 4.29E-08 -0.329 3.83E-04
ILMN_ .1683456 6354 CCL7 3.750 1.63E-22 -3.006 1.93E-21
ILMN_ .1683598 2182 ACSL4 0.805 1.41E-11 -0.342 7.79E-05
ILMN_ .1683792 51056 LAP3 1.884 3.04E-20 -0.355 4.89E-05
ILMN_ .1683950 29916 SNX11 1.319 7.16E-18 -0.333 4.04E-05
ILMN_ .1684054 427 ASAH1 0.378 3.03E-05 -0.322 1.77E-04
ILMN_ .1684368 85027 C5orf62 0.982 5.27E-13 -0.784 2.98E-11
ILMN_ .1684887 64092 SAMSN1 2.133 5.35E-20 -2.273 3.14E-21
ILMN_ .1685005 7132 TNFRSF1A 0.430 1.70E-06 -0.577 1.55E-08
ILMN_ .1685095 55330 CNO 0.510 8.73E-06 -0.330 1.33E-03
ILMN_ .1685493 57458 TMCC3 1.140 1.46E-13 -0.348 3.51E-04
ILMN_ .1685540 57619 SHRM 1.121 2.20E-11 -0.540 6.39E-08
ILMN_ .1685824 9334 B4GALT5 1.028 1.11E-14 -0.522 3.60E-08
ILMN_ .1686573 1672 DEFB1 0.810 6.81E-11 -1.354 4.18E-16
ILMN_ .1686623 1436 CSF1R 1.965 2.82E-22 -0.578 3.26E-09
ILMN_ .1686805 1398 CRK 0.504 1.70E-06 -0.251 5.23E-03
ILMN_ .1686989 3638 INSIG1 0.543 1.83E-07 -0.384 3.14E-05
ILMN_ .1687301 1462 VCAN 1.239 1.79E-14 -1.791 1.18E-18
ILMN_ .1687403 64976 MRPL40 1.140 9.77E-16 -0.553 9.84E-09
ILMN_ 1687440 28996 HIPK2 1.016 7.41E-12 -0.328 4.85E-04
ILMN_ .1687501 26002 MOXD1 1.439 2.78E-17 -0.522 2.15E-07
ILMN_ .1687519 8773 SNAP23 0.334 5.20E-04 -0.280 2.72E-03
ILMN_ .1687533 10507 SEMA4D 0.933 1.37E-12 -0.774 9.30E-11
ILMN_ .1687768 135112 NCOA7 2.977 4.02E-27 -0.488 1.02E-07
ILMN_ .1688480 595 CCND1 2.189 6.57E-21 -0.266 3.77E-03
ILMN_ .1688775 284207 METRNL 1.658 4.78E-17 -0.288 2.58E-03
ILMN_ .1689371 26157 GIMAP2 1.289 9.71E-16 -0.586 1.64E-08
ILMN_ .1689518 5175 PEC AMI 0.537 3.77E-07 -0.341 2.80E-04
ILMN_ .1689578 7098 TLR3 1.092 1.64E-14 -0.303 4.11E-04
ILMN_ .1689585 25943 C20orfl94 0.215 5.70E-03 -0.607 5.36E-09
ILMN_ .1689836 728 C5AR1 2.732 1.31E-22 -0.856 2.27E-11
ILMN_ .1689842 6307 SC4MOL 0.987 2.40E-14 -0.244 1.26E-03
ILMN_ .1689953 975 CD81 0.782 1.41E-11 -0.328 9.46E-05
ILMN_ .1689968 80301 PLEKH02 2.397 8.21E-22 -0.367 1.28E-04
ILMN_ .1689989 9578 CDC42BPB 0.407 1.48E-05 -0.237 5.82E-03
ILMN_ .1690145 653930 LOC653930 0.702 1.66E-07 -0.327 3.14E-03
ILMN_ .1690174 54567 DLL4 1.696 3.34E-16 -0.714 7.98E-08
ILMN_ .1690241 116071 BATF2 3.275 7.11E-27 -0.756 1.28E-10
ILMN_ .1690253 79933 SYNP02L 0.552 1.24E-06 -0.391 1.81E-04
ILMN_ .1690566 83937 RASSF4 1.188 5.02E-17 -0.586 1.79E-09
ILMN_ .1690621 84059 GPR98 0.284 1.20E-02 -0.367 2.67E-04 ILMN_ 1690844 387820 LOC387820 0.809 8.03E-12 -0.525 9.73E-08
ILMN_ .1691334 51314 TXNDC3 0.252 8.44E-03 -0.341 1.29E-04
ILMN_ .1691339 51267 CLEC1A 0.435 1.65E-05 -0.315 5.29E-04
ILMN_ .1691341 3575 IL7R 3.770 5.29E-25 -0.968 2.64E-10
ILMN_ .1691364 6772 STAT1 2.847 1.86E-26 -0.219 3.93E-03
ILMN_ .1691376 182 JAG1 0.480 2.90E-06 -0.254 3.35E-03
ILMN_ .1691535 8450 CUL4B 0.422 1.12E-05 -0.354 1.23E-04
ILMN_ .1691575 6643 SNX2 0.954 3.07E-13 -0.226 5.36E-03
ILMN_ .1691717 79651 RHBDF2 2.726 1.37E-23 -0.912 2.41E-12
ILMN_ .1691772 146050 ZSCAN29 0.460 4.04E-06 -0.262 3.38E-03
ILMN_ .1692056 9955 HS3ST3A1 1.656 2.58E-18 -1.182 1.77E-15
ILMN_ .1692058 4692 NDN 0.521 4.69E-06 -0.309 4.10E-04
ILMN_ .1692225 79930 DOK3 0.338 1.78E-04 -0.392 3.65E-05
ILMN_ .1692280 4821 NKX2-2 0.968 2.53E-13 -0.884 2.56E-12
ILMN_ .1692295 64005 MY01G 0.378 2.08E-05 -1.060 1.81E-14
ILMN_ .1692335 2004 ELK3 0.242 1.24E-02 -0.300 2.49E-03
ILMN_ .1692398 8506 CNTNAP1 1.157 4.03E-15 -0.426 3.58E-06
ILMN_ .1692464 55020 FLJ20699 0.382 1.47E-05 -0.414 6.43E-06
ILMN_ .1692539 23616 SH3BP1 0.993 2.06E-13 -0.509 3.63E-07
ILMN_ .1692731 80727 TTYH3 1.174 2.18E-15 -0.535 1.14E-07
ILMN_ .1692742 22898 DENND3 1.121 6.41E-14 -0.467 1.87E-06
ILMN_ .1692865 155382 VPS37D 0.819 3.67E-10 -0.256 3.29E-03
ILMN_ .1693009 10875 FGL2 1.843 2.48E-19 -0.926 5.02E-12
ILMN_ .1693334 5033 P4HA1 0.552 2.11E-07 -0.365 7.62E-05
ILMN_ .1693338 1545 CYP1B 1 0.495 9.38E-07 -1.843 1.02E-19
ILMN_ .1693431 144811 C13orf31 2.956 5.75E-23 -1.311 3.94E-14
ILMN_ .1693552 11314 CD300A 0.746 5.63E-09 -0.487 6.70E-06
ILMN_ .1693630 9605 C16orf7 0.803 4.70E-11 -0.389 3.04E-05
ILMN_ .1693771 444 ASPH 0.303 7.85E-04 -0.419 2.08E-05
ILMN_ .1693826 84868 HAVCR2 4.600 8.94E-30 -1.262 8.19E-16
ILMN_ .1694058 340198 IFITM4P 0.464 1.30E-05 -0.251 5.90E-03
ILMN_ 1694140 134265 AFAP1L1 0.264 9.43E-03 -0.287 3.22E-03
ILMN_ .1694213 51177 PLEKHOl 2.730 1.69E-23 -1.037 6.19E-13
ILMN_ .1694249 947 CD34 0.273 8.48E-03 -0.272 8.25E-03
ILMN_ 1694466 9189 ZBED1 1.450 1.09E-17 -0.450 2.45E-06
ILMN_ .1694980 4669 NAGLU 0.500 3.24E-06 -0.443 2.49E-05
ILMN_ .1695058 92745 SLC38A5 0.449 1.98E-05 -0.788 5.07E-10
ILMN_ .1695246 200942 KLHDC8B 1.654 1.35E-15 -0.748 3.99E-09
ILMN_ .1695290 10979 FERMT2 1.658 1.70E-18 -0.660 3.75E-09
ILMN_ .1695311 3108 HLA-DMA 0.679 5.70E-09 -0.308 9.26E-04
ILMN_ .1695316 64116 SLC39A8 1.023 1.20E-11 -0.515 6.31E-06
ILMN_ .1695354 90427 BMF 1.902 2.23E-19 -0.925 1.39E-12
ILMN_ .1695435 653610 LOC653610 1.443 8.01E-16 -0.659 5.83E-09
ILMN_ .1695485 286333 C9orfl09 0.509 5.60E-06 -0.696 1.57E-08 ILMN_ .1695583 644094 LOC644094 0.249 8.67E-03 -0.270 2.47E-03
ILMN_ .1696317 93589 CACNA2D4 0.415 4.44E-06 -0.399 7.84E-06
ILMN_ .1696360 1508 CTSB 3.100 5.34E-24 -1.341 7.87E-15
ILMN_ .1696419 2040 STOM 0.800 1.52E-11 -0.475 6.64E-07
ILMN_ .1696537 115265 DDIT4L 4.958 1.05E-30 -2.364 1.54E-22
ILMN_ .1696591 5925 RBI 0.637 2.81E-08 -0.326 6.68E-04
ILMN_ .1696622 145389 SLC38A6 1.395 2.13E-15 -0.490 5.39E-06
ILMN_ .1696654 24138 IFIT5 1.960 5.22E-19 -0.350 3.85E-04
ILMN_ .1697153 23390 ZDHHC17 0.883 4.28E-12 -0.360 7.60E-05
ILMN_ .1697268 84034 EMILIN2 0.608 1.06E-09 -0.679 2.01E-10
ILMN_ .1697309 653361 NCF1 4.145 1.13E-24 -0.930 7.78E-10
ILMN_ .1697409 8764 TNFRSF14 1.755 1.11E-19 -0.659 2.24E-09
ILMN_ .1697499 3127 HLA-DRB5 0.862 7.92E-11 -0.631 4.41E-08
ILMN_ .1697554 54440 SASH3 0.941 4.38E-14 -0.735 1.93E-11
ILMN_ .1697817 24145 PANX1 1.661 6.88E-17 -0.258 7.28E-03
ILMN_ .1697864 159013 CXorf38 1.531 1.36E-18 -0.418 2.34E-06
ILMN_ .1697971 10475 TRIM38 0.821 4.18E-12 -0.249 1.29E-03
ILMN_ .1698015 6899 TBX1 1.031 4.13E-11 -0.567 3.94E-07
ILMN_ .1698019 5641 LGMN 3.074 1.05E-25 -0.469 1.14E-06
ILMN_ .1698243 112770 Clorf85 0.438 6.54E-07 -0.384 8.86E-06
ILMN_ .1698313 1368 CPM 0.379 1.09E-04 -0.259 2.79E-03
ILMN_ .1698323 55041 PLEKHB2 0.371 2.53E-04 -0.498 3.44E-06
ILMN_ .1698487 6392 SDHD 0.193 8.98E-03 -0.224 3.51E-03
ILMN_ .1699022 23052 ENDOD1 1.281 5.87E-14 -0.422 8.05E-05
ILMN_ .1699496 51317 PHF21A 0.773 2.41E-11 -0.211 6.50E-03
ILMN_ .1699570 7165 TPD52L2 0.979 3.19E-13 -0.488 7.05E-07
ILMN_ .1699574 8829 NRP1 2.381 4.55E-22 -0.316 4.85E-04
ILMN_ .1699636 22985 ACINI 0.259 1.38E-03 -0.397 9.23E-06
ILMN_ .1699651 3569 IL6 1.065 7.91E-13 -0.852 l.OlE-10
ILMN_ .1699806 646426 LOC646426 0.241 7.30E-03 -0.232 8.58E-03
ILMN_ .1699829 1490 CTGF 1.500 2.38E-16 -0.325 3.14E-04
ILMN_ .1699856 5900 RALGDS 1.573 2.29E-18 -1.072 5.11E-14
ILMN_ .1699908 3594 IL12RB1 0.600 1.98E-06 -0.304 3.68E-03
ILMN_ .1700031 23532 PRAME 0.525 5.98E-08 -0.777 2.72E-11
ILMN_ .1700081 10468 FST 1.566 1.97E-17 -1.157 2.16E-14
ILMN_ .1700180 643930 LOC643930 1.526 1.68E-11 -0.529 2.73E-05
ILMN_ .1700276 51528 C14orfl00 0.258 1.49E-03 -0.257 1.92E-03
ILMN_ .1700428 3112 HLA-DOB 0.309 5.77E-03 -0.386 4.69E-04
ILMN_ .1700610 64581 CLEC7A 0.256 1.47E-03 -0.248 2.44E-03
ILMN_ .1700628 57062 DDX24 0.273 1.76E-03 -0.289 1.28E-03
ILMN_ .1700811 56061 UBFD1 1.226 2.05E-15 -0.347 1.48E-04
ILMN_ .1700967 151963 C3orf59 0.903 2.47E-12 -0.361 5.83E-05
ILMN_ .1701094 2055 CLN8 0.402 1.69E-05 -0.297 7.80E-04
ILMN_ .1701195 7941 PLA2G7 2.581 4.76E-24 -1.401 1.62E-17 ILMN_ .1701455 26270 FBX06 1.956 2.02E-21 -0.229 4.50E-03
ILMN_ .1701551 23460 ABCA6 1.009 3.83E-11 -0.956 2.34E-11
ILMN_ .1701621 9997 SC02 1.387 1.56E-16 -0.491 1.21E-06
ILMN_ .1701655 80024 SLC24A6 0.450 1.76E-06 -0.257 2.27E-03
ILMN_ .1701854 2787 GNG5 0.286 5.09E-04 -0.350 2.82E-05
ILMN_ .1701877 558 AXL 2.201 2.68E-22 -0.355 5.98E-05
ILMN_ .1701911 140947 C5orf20 2.178 6.44E-23 -1.820 5.81E-21
ILMN_ .1701914 29126 CD274 1.303 8.09E-14 -0.297 1.17E-03
ILMN_ .1702237 2280 FKBP1A 0.309 2.43E-04 -0.277 6.93E-04
ILMN_ .1702501 6196 RPS6KA2 2.898 1.61E-23 -0.674 2.16E-09
ILMN_ .1702585 646817 LOC646817 0.468 3.26E-05 -0.399 2.20E-04
ILMN_ .1702787 64218 SEMA4A 2.253 1.74E-20 -0.853 2.71E-10
ILMN_ .1703178 7857 SCG2 0.797 6.63E-09 -0.672 1.90E-08
ILMN_ .1703180 2117 ETV3 0.300 2.53E-04 -0.339 7.64E-05
ILMN_ .1703314 79786 KLHL36 0.559 1.33E-06 -0.428 3.82E-05
ILMN_ .1703335 114294 LACTB 2.269 1.53E-21 -0.538 3.24E-07
ILMN_ .1703558 2275 FHL3 1.152 5.49E-11 -0.334 2.33E-03
ILMN_ .1703572 64881 PCDH20 0.674 1.46E-08 -0.555 5.14E-07
ILMN_ .1703617 10598 AHSA1 0.220 1.18E-02 -0.773 4.34E-10
ILMN_ .1703622 5479 PPIB 0.379 2.52E-03 -0.435 6.20E-04
ILMN_ .1703650 10318 TNIP1 1.445 4.76E-17 -0.278 1.52E-03
ILMN_ .1703791 310 ANXA7 0.491 2.03E-07 -0.318 1.73E-04
ILMN_ .1703926 5732 PTGER2 0.462 3.99E-05 -0.279 4.49E-03
ILMN_ .1703955 114907 FBX032 2.112 2.02E-19 -0.751 5.89E-09
ILMN_ .1704139 207063 DHRSX 0.548 7.21E-08 -0.528 1.14E-07
ILMN_ 1704164 23400 ATP13A2 0.623 5.63E-06 -0.378 4.51E-04
ILMN_ .1704290 9517 SPTLC2 0.564 5.30E-08 -0.407 1.69E-05
ILMN_ .1704369 51474 LIMA1 0.889 1.86E-12 -1.100 1.43E-14
ILMN_ .1704550 51582 AZIN1 0.358 1.24E-04 -0.313 6.37E-04
ILMN_ .1704713 53944 CSNK1G1 0.568 6.50E-07 -0.285 2.53E-03
ILMN_ .1704985 1593 CYP27A1 1.758 1.42E-17 -0.378 2.84E-04
ILMN_ .1705224 375346 TMEM110 1.584 1.13E-15 -0.480 7.87E-07
ILMN_ .1705302 2217 FCGRT 0.191 1.22E-02 -0.295 4.10E-04
ILMN_ .1705663 23312 DMXL2 2.146 1.46E-21 -0.827 1.37E-11
ILMN_ .1705750 7052 TGM2 1.034 1.29E-11 -0.356 8.00E-04
ILMN_ .1705874 642093 LOC642093 1.546 5.80E-14 -0.763 1.80E-07
ILMN_ .1705907 9972 NUP153 0.307 1.01E-03 -0.275 2.52E-03
ILMN_ .1705953 91694 L0NRF1 0.726 8.94E-10 -0.238 5.47E-03
ILMN_ 1706434 440359 LOC440359 0.204 1.13E-02 -0.597 2.10E-08
ILMN_ .1706498 29940 DSE 2.035 3.39E-19 -0.895 1.30E-10
ILMN_ .1706521 1455 CSNK1G2 0.264 1.41E-03 -0.373 2.40E-05
ILMN_ .1706645 115004 C6orfl50 1.197 6.30E-13 -0.435 5.98E-05
ILMN_ .1707051 4772 NFATC1 1.194 4.84E-15 -1.051 1.21E-13
ILMN_ .1707088 79961 DENND2D 0.615 1.92E-07 -0.389 5.63E-05 ILMN_ .1707292 339210 C17orf67 1.013 2.41E-13 -0.295 8.11E-04
ILMN_ .1707513 54858 PGPEP1 0.795 3.70E-10 -0.408 2.56E-05
ILMN_ .1707591 79931 TNIP3 1.250 1.95E-15 -0.605 1.45E-08
ILMN_ .1707695 3434 IFIT1 4.451 2.33E-29 -0.314 5.11E-04
ILMN_ .1707727 51129 ANGPTL4 1.063 2.02E-12 -0.270 4.74E-03
ILMN_ .1707945 92797 HELB 0.669 7.37E-09 -0.307 7.61E-04
ILMN_ .1707975 3053 SERPIND1 0.368 1.51E-03 -0.469 3.07E-05
ILMN_ .1708110 55314 TMEM144 0.978 1.42E-12 -0.305 7.46E-04
ILMN_ .1708248 10859 LILRB1 1.286 4.45E-15 -0.572 2.35E-07
ILMN_ .1708721 9910 RABGAP1L 1.767 8.09E-20 -0.438 1.88E-06
ILMN_ .1708728 55766 H2AFJ 0.992 3.95E-13 -0.233 6.29E-03
ILMN_ .1708881 55647 RAB20 1.306 3.18E-17 -0.210 6.44E-03
ILMN_ .1708922 25 ABL1 0.293 3.05E-03 -0.341 6.61E-04
ILMN_ 1709044 60436 TGIF2 0.262 9.04E-04 -0.238 2.69E-03
ILMN_ .1709153 51334 PRR16 2.376 1.61E-22 -1.435 4.43E-17
ILMN_ .1709583 644019 LOC644019 0.258 5.31E-03 -0.536 9.83E-07
ILMN_ .1709630 203260 CCDC107 0.431 1.32E-04 -0.388 3.68E-04
ILMN_ .1709750 64420 SUSD1 0.391 6.38E-06 -0.209 7.49E-03
ILMN_ .1709820 313 AOAH 0.339 5.90E-04 -0.298 2.21E-03
ILMN_ .1709894 10845 CLPX 0.270 1.10E-03 -0.341 1.11E-04
ILMN_ .1709937 3783 KCNN4 1.776 8.14E-19 -0.690 1.70E-09
ILMN_ .1710092 140685 ZBTB46 1.151 2.29E-16 -0.217 3.83E-03
ILMN_ .1710221 2859 GPR35 0.711 l.lOE-10 -0.319 9.60E-05
ILMN_ .1710514 602 BCL3 3.415 7.16E-27 -0.523 2.94E-07
ILMN_ .1710740 717 C2 1.702 1.02E-18 -0.608 2.69E-08
ILMN_ .1710906 153830 RNF145 0.576 1.07E-06 -0.263 5.35E-03
ILMN_ .1710923 57823 SLAMF7 2.171 7.17E-20 -0.335 3.34E-04
ILMN_ .1711102 10678 B3GNT2 0.256 2.12E-03 -0.233 4.12E-03
ILMN_ .1711223 649362 LOC649362 0.971 4.31E-10 -0.558 5.10E-07
ILMN_ .1711331 440738 MAP1LC3C 0.525 4.11E-05 -0.684 7.81E-08
ILMN_ .1711332 22797 TFEC 1.110 3.47E-13 -0.400 9.24E-05
ILMN_ .1711383 6789 STK4 0.746 3.36E-10 -0.307 5.02E-04
ILMN_ .1711703 80262 C16orf70 1.325 2.31E-16 -0.735 5.97E-11
ILMN_ .1711909 55741 EDEM2 0.773 1.06E-10 -0.264 1.41E-03
ILMN_ .1711994 10312 TCIRG1 0.610 1.11E-08 -0.528 2.37E-07
ILMN_ .1712639 84883 AIFM2 0.749 1.24E-10 -0.312 3.36E-04
ILMN_ .1712673 23328 SASH1 1.510 3.98E-19 -0.812 3.57E-12
ILMN_ .1712684 56975 FAM20C 1.139 1.53E-14 -0.359 8.62E-05
ILMN_ .1712888 10808 HSPH1 0.224 8.42E-03 -0.394 3.66E-05
ILMN_ .1712914 10501 SEMA6B 0.430 7.30E-05 -0.386 6.39E-05
ILMN_ .1712944 166 AES 0.305 3.36E-03 -0.297 4.37E-03
ILMN_ .1713058 9050 PSTPIP2 1.784 4.47E-21 -1.520 3.51E-19
ILMN_ .1713156 10943 MSL3L1 0.469 5.01E-07 -0.209 6.72E-03
ILMN_ .1713182 653879 LOC653879 1.326 8.39E-15 -0.399 4.72E-05 ILMN_ .1713285 8775 NAPA 1.011 1.19E-11 -0.456 1.09E-05
ILMN_ .1713496 8869 ST3GAL5 1.975 7.63E-21 -0.932 5.50E-13
ILMN_ .1713505 4864 NPC1 1.340 1.54E-16 -0.465 1.28E-06
ILMN_ .1713542 9830 TRIM 14 0.561 6.85E-06 -0.309 2.41E-03
ILMN_ .1713603 5579 PRKCB1 0.480 6.56E-07 -0.496 2.55E-07
ILMN_ .1713715 83902 KRTAP17-1 0.256 5.44E-03 -0.306 1.46E-03
ILMN_ .1713751 8728 ADAM 19 0.662 2.08E-09 -0.454 1.76E-06
ILMN_ .1713759 51465 UBE2J1 0.599 3.79E-09 -0.425 2.52E-06
ILMN_ .1713952 55765 Clorfl06 0.990 1.20E-14 -0.710 3.28E-11
ILMN_ .1714165 6483 ST3GAL2 0.986 4.29E-12 -0.247 6.68E-03
ILMN_ .1714401 81609 SNX27 0.528 6.77E-08 -0.430 2.98E-06
ILMN_ .1714402 54877 ZCCHC2 0.645 1.13E-07 -0.304 1.02E-03
ILMN_ .1714600 89795 NAV3 1.770 9.60E-18 -1.152 1.36E-13
ILMN_ .1714602 942 CD86 1.376 1.03E-16 -0.670 6.91E-10
ILMN_ .1715024 4047 LSS 0.332 2.74E-04 -0.469 3.70E-06
ILMN_ .1715131 1236 CCR7 4.204 1.79E-26 -0.507 2.46E-05
ILMN_ .1715169 3123 HLA-DRB 1 0.769 8.82E-10 -0.380 7.43E-05
ILMN_ .1715173 6195 RPS6KA1 0.375 1.28E-04 -0.488 3.93E-06
ILMN_ .1715175 4233 MET 0.554 1.53E-07 -0.364 1.07E-04
ILMN_ .1715543 641371 ACOT1 0.716 8.56E-09 -0.477 1.12E-05
ILMN_ .1715635 8992 ATP6V0E1 0.771 6.29E-11 -0.286 9.08E-04
ILMN_ .1716237 10965 ACOT2 0.633 3.79E-06 -0.338 9.50E-04
ILMN_ .1716264 27063 ANKRD1 0.410 4.64E-04 -0.289 6.37E-03
ILMN_ .1716276 388372 CCL4L2 7.223 1.95E-32 -0.539 1.48E-05
ILMN_ .1716546 201252 FLJ23754 0.351 1.32E-03 -0.378 6.46E-04
ILMN_ .1716547 55577 NAGK 1.871 1.13E-19 -0.236 2.53E-03
ILMN_ .1716704 84166 NLRC5 0.879 3.94E-11 -0.458 5.56E-06
ILMN_ .1716736 941 CD80 3.494 4.68E-26 -0.462 8.18E-06
ILMN_ .1716859 6999 TD02 7.345 7.22E-33 -5.071 2.77E-30
ILMN_ .1716862 5495 PPM1B 0.311 3.72E-04 -0.503 5.80E-07
ILMN_ .1717180 9107 MTMR6 0.266 1.48E-03 -0.282 8.19E-04
ILMN_ .1717207 64386 MMP25 1.205 3.52E-16 -1.004 3.88E-14
ILMN_ .1717229 195827 C9orf21 0.675 2.64E-09 -0.358 2.75E-05
ILMN_ .1717261 3125 HLA-DRB 3 0.753 9.74E-11 -0.397 1.51E-05
ILMN_ .1717262 10544 PROCR 1.048 1.63E-13 -1.066 4.59E-14
ILMN_ .1717313 4794 NFKBIE 1.416 1.67E-17 -0.312 2.51E-04
DKFZp6860132
ILMN_ .1717482 401014 0.685 1.23E-06 -0.298 7.48E-03
ILMN_ .1717594 91056 DKFZp761E198 0.517 1.03E-05 -0.302 3.88E-03
ILMN_ .1717639 150094 SIK1 1.003 3.19E-13 -0.279 4.00E-04
ILMN_ .1718303 5819 PVRL2 1.476 2.52E-17 -0.616 1.88E-08
ILMN_ .1718552 10563 CXCL13 5.539 1.47E-26 -4.228 8.39E-24
ILMN_ .1718558 64761 PARP12 2.620 4.01E-25 -0.219 4.48E-03
ILMN_ .1718734 4302 MLLT6 1.041 6.66E-14 -0.318 2.23E-04 ILMN_ .1719286 5476 CTSA 0.395 1.75E-05 -0.321 2.65E-04
ILMN_ .1719543 4094 MAF 0.668 2.64E-09 -0.302 1.92E-04
ILMN_ .1719627 11000 SLC27A3 0.224 5.35E-03 -0.416 6.41E-06
ILMN_ .1719649 9725 TMEM63A 0.992 3.21E-14 -0.523 5.01E-08
ILMN_ .1720048 6347 CCL2 7.717 2.54E-33 -2.468 1.01E-20
ILMN_ .1720083 30844 EHD4 1.368 2.42E-17 -0.907 6.66E-13
ILMN_ .1720344 81614 NIPA2 0.224 6.32E-03 -0.476 7.68E-07
ILMN_ .1720452 79836 LONRF3 0.866 5.82E-12 -0.517 3.12E-07
ILMN_ .1720496 2977 GUCY1A2 0.439 6.50E-06 -0.279 1.17E-03
ILMN_ .1721113 3107 HLA-C 1.301 7.04E-18 -0.225 2.56E-03
ILMN_ .1721134 7051 TGM1 0.475 5.34E-06 -0.290 1.21E-03
ILMN_ .1721316 8797 TNFRSF10A 0.627 4.85E-08 -0.312 9.46E-04
ILMN_ .1721344 126308 MOBKL2A 0.294 2.27E-04 -0.438 1.08E-06
ILMN_ .1721575 57617 VPS 18 0.645 2.99E-09 -0.324 2.02E-04
ILMN_ .1721762 8807 IL18RAP 0.906 2.53E-10 -0.674 9.22E-08
ILMN_ .1721921 642 BLMH 0.223 9.19E-03 -0.322 4.46E-04
ILMN_ .1722218 79143 MBOAT7 0.895 1.35E-11 -0.758 2.83E-10
ILMN_ .1722622 9332 CD 163 3.030 2.88E-24 -2.597 5.30E-23
ILMN_ .1722898 6423 SFRP2 0.319 2.59E-04 -0.271 9.61E-04
ILMN_ .1723004 971 CD72 0.621 3.10E-08 -0.425 2.00E-05
ILMN_ .1723035 4973 OLR1 1.424 9.33E-16 -0.985 5.10E-12
ILMN_ .1723139 2820 GPD2 1.054 1.16E-11 -0.580 1.69E-06
ILMN_ .1723412 430 ASCL2 0.929 8.66E-13 -0.390 2.37E-05
ILMN_ .1723480 684 BST2 0.958 4.74E-12 -0.347 2.48E-04
ILMN_ .1723486 3099 HK2 0.975 2.73E-13 -0.524 1.14E-07
ILMN_ .1723536 23032 USP33 0.389 6.42E-06 -0.269 8.00E-04
ILMN_ .1723674 286183 NKAIN3 0.244 7.16E-03 -0.363 2.09E-04
ILMN_ .1723846 25895 FAM119B 1.094 3.64E-13 -0.507 1.95E-06
ILMN_ .1723969 23236 PLCB1 1.206 4.73E-14 -0.572 1.89E-07
ILMN_ .1724139 114908 TMEM123 0.924 1.95E-12 -0.218 8.24E-03
ILMN_ .1724234 7442 TRPV1 0.340 1.04E-03 -0.288 4.72E-03
ILMN_ .1724333 27348 TOR IB 2.151 1.82E-22 -0.541 5.78E-08
ILMN_ .1724493 256586 LYSMD2 1.923 1.62E-20 -0.775 1.23E-10
ILMN_ .1724533 23643 LY96 2.933 6.80E-25 -0.850 1.13E-11
ILMN_ .1724658 664 BNIP3 0.353 7.28E-03 -0.901 5.74E-09
ILMN_ .1724837 56829 ZC3HAV1 1.296 6.35E-15 -0.453 1.43E-05
ILMN_ .1725314 2635 GBP3 1.772 1.32E-17 -0.581 6.21E-07
ILMN_ .1725320 6614 SIGLECl 1.813 6.43E-18 -0.333 6.98E-04
ILMN_ .1725518 83854 ANGPTL6 0.927 1.14E-11 -0.631 7.95E-09
ILMN_ .1725666 2967 GTF2H3 0.388 1.91E-05 -0.264 1.44E-03
ILMN_ .1725700 4343 MOV 10 1.574 9.68E-19 -0.388 1.86E-05
ILMN_ .1726107 7335 UBE2V1 0.390 2.16E-04 -0.260 2.06E-03
ILMN_ .1726189 84689 MS4A14 1.302 4.41E-16 -0.602 2.59E-08
ILMN_ .1726289 55196 C12orf35 1.286 6.27E-16 -0.901 3.19E-12 ILMN_ .1726448 4312 MMP1 0.437 3.55E-04 -0.459 1.51E-04
ILMN_ .1726704 6248 RSC1A1 0.918 1.07E-11 -0.274 1.74E-03
ILMN_ .1726873 219931 TPCN2 0.594 5.28E-08 -0.252 4.36E-03
ILMN_ .1726906 84335 AKT1S1 0.942 1.06E-11 -0.278 2.12E-03
ILMN_ .1727045 25780 RASGRP3 2.402 2.47E-22 -1.578 6.98E-18
ILMN_ .1727249 253725 FAM21C 0.582 8.66E-08 -0.305 3.41E-04
ILMN_ .1727524 8754 ADAM9 1.323 7.26E-17 -0.498 1.21E-07
ILMN_ .1727567 10215 OLIG2 1.636 4.59E-19 -1.301 1.44E-16
ILMN_ .1728009 134285 TMEM171 2.029 1.84E-19 -0.750 7.95E-11
ILMN_ .1728019 5371 PML 0.888 5.47E-10 -0.419 1.59E-05
ILMN_ .1728224 11054 OGFR 1.061 2.36E-14 -0.480 2.16E-07
ILMN_ .1728236 55106 SLFN12 0.802 1.04E-09 -0.473 2.55E-06
ILMN_ .1728349 55362 TMEM63B 0.456 6.29E-05 -0.362 6.65E-04
ILMN_ .1728724 23765 IL17RA 0.340 3.04E-04 -0.595 8.66E-08
ILMN_ .1728975 6341 SCOl 0.340 1.15E-04 -0.290 8.02E-04
ILMN_ .1728999 730273 LOC730273 0.432 1.30E-04 -0.332 1.37E-03
ILMN_ .1729123 5524 PPP2R4 0.230 8.81E-03 -0.541 3.93E-07
ILMN_ .1729130 55069 C7orf42 0.321 9.34E-05 -0.330 8.10E-05
ILMN_ .1729144 9166 EBAG9 0.302 2.54E-03 -0.307 5.97E-04
ILMN_ .1729197 400879 LOC400879 0.492 1.19E-07 -0.255 9.99E-04
ILMN_ .1729294 55819 RNF130 0.729 1.30E-10 -0.695 5.54E-10
ILMN_ .1729487 2766 GMPR 2.450 4.67E-22 -0.542 5.03E-07
ILMN_ .1729515 5303 PIN4 0.366 7.38E-05 -0.227 7.47E-03
ILMN_ .1729596 64423 INF2 0.368 3.34E-04 -0.473 1.50E-05
ILMN_ .1729749 51191 HERC5 3.379 7.63E-28 -0.252 1.62E-03
ILMN_ .1729987 6714 SRC 3.346 9.94E-24 -0.527 6.97E-06
ILMN_ .1730032 666 BOK 1.641 9.89E-19 -0.706 6.27E-10
ILMN_ .1730159 497189 TIFAB 2.204 9.74E-23 -0.755 6.54E-11
ILMN_ .1730433 23607 CD2AP 0.581 1.37E-06 -0.285 4.74E-03
ILMN_ .1730491 114793 FMNL2 2.633 5.51E-23 -1.017 5.66E-13
ILMN_ .1730504 56895 AGPAT4 1.362 1.03E-14 -0.589 1.61E-07
ILMN_ .1730710 140 ADORA3 1.049 1.77E-11 -1.228 2.61E-14
ILMN_ .1730917 8564 KMC) 1.113 1.23E-12 -0.634 5.75E-09
ILMN_ .1731048 7096 TLR1 2.455 7.70E-21 -0.855 6.51E-10
ILMN_ .1731181 55852 TEX2 0.613 8.63E-10 -0.441 6.65E-07
ILMN_ .1731358 55205 ZNF532 0.283 7.22E-04 -0.322 2.57E-04
ILMN_ .1731991 57410 SCYL1 0.203 7.79E-03 -0.477 4.04E-07
ILMN_ .1732080 474338 SUM01P3 0.247 7.07E-03 -0.282 2.50E-03
ILMN_ .1732151 1291 COL6A1 1.747 8.20E-18 -1.112 1.24E-13
ILMN_ .1732410 220963 SLC16A9 0.581 7.88E-09 -0.459 6.11E-07
ILMN_ .1732609 80256 KIAA1539 0.885 1.30E-11 -0.578 7.86E-08
ILMN_ .1732967 170954 KIAA1949 1.081 2.01E-13 -0.676 8.64E-09
ILMN_ .1733136 3449 IFNA16 2.363 5.80E-19 -0.506 5.22E-05
ILMN_ .1733176 3987 LIMS1 0.847 7.47E-12 -0.863 5.59E-12 ILMN_ .1733249 59345 GNB4 0.583 1.99E-05 -0.475 4.32E-05
ILMN_ .1733453 284988 LOC284988 1.449 1.62E-15 -0.327 1.28E-03
ILMN_ .1733515 84695 LOXL3 0.276 1.02E-03 -0.321 2.07E-04
ILMN_ .1733535 167465 ZNF366 2.145 7.49E-22 -0.269 8.12E-04
ILMN_ .1733675 4354 MPP1 1.133 4.72E-15 -0.683 7.19E-10
ILMN_ .1733756 1303 COL12A1 0.236 8.73E-03 -0.308 1.02E-03
ILMN_ .1733874 9047 SH2D2A 0.764 4.79E-09 -0.309 2.39E-03
ILMN_ .1733970 573 BAG1 0.379 8.44E-04 -0.601 1.37E-07
ILMN_ .1734316 10730 YME1L1 0.389 1.10E-05 -0.227 4.56E-03
ILMN_ 1734440 63894 C14orfl33 0.234 2.05E-03 -0.347 3.54E-05
ILMN_ 1734694 4225 MEP1B 0.736 2.33E-09 -0.429 1.43E-05
ILMN_ .1734814 3308 HSPA4 0.342 7.72E-04 -0.855 3.16E-10
ILMN_ .1734830 4524 MTHFR 0.818 7.40E-12 -0.215 5.00E-03
ILMN_ .1734895 113402 SFT2D1 0.287 3.79E-04 -0.283 3.87E-04
ILMN_ .1735014 1316 KLF6 2.394 8.80E-23 -0.305 5.57E-04
ILMN_ .1735143 9473 Clorf38 0.621 8.79E-06 -0.328 1.40E-03
ILMN_ .1735584 29906 ST8SIA5 0.658 9.40E-08 -0.757 3.04E-09
ILMN_ .1735764 3357 HTR2B 2.060 2.30E-19 -1.361 1.17E-15
ILMN_ .1736048 8178 ELL 0.477 5.70E-07 -0.406 7.88E-06
ILMN_ .1736112 79658 ARHGAP10 0.738 1.70E-09 -0.325 5.81E-04
ILMN_ .1736311 5452 POU2F2 0.622 3.23E-06 -0.336 3.12E-03
ILMN_ .1736510 3344 FOXN2 0.355 3.04E-05 -0.293 4.11E-04
ILMN_ .1736548 65979 PHACTR4 1.337 1.17E-16 -0.396 1.24E-05
ILMN_ .1736704 85458 DIXDCl 0.329 8.08E-03 -0.456 4.78E-04
ILMN_ .1736742 23127 GLT25D2 0.640 1.18E-07 -0.400 8.02E-05
ILMN_ .1736757 79158 GNPTAB 0.625 7.01E-07 -0.415 2.05E-04
ILMN_ .1736939 7357 UGCG 1.357 8.01E-15 -0.391 1.21E-04
ILMN_ .1736954 51043 ZBTB7B 0.560 4.08E-07 -0.293 2.00E-03
ILMN_ .1737314 604 BCL6 3.561 2.03E-25 -0.431 6.50E-05
ILMN_ .1738075 80790 CMIP 0.574 2.04E-09 -0.290 2.25E-04
ILMN_ .1738523 4615 MYD88 1.884 1.58E-20 -0.433 3.75E-06
ILMN_ .1738552 6507 SLC1A3 2.626 2.86E-24 -1.388 6.87E-17
ILMN_ .1738558 8601 RGS20 1.628 1.07E-17 -0.439 1.27E-05
ILMN_ .1738675 5777 PTPN6 0.737 1.70E-09 -0.425 2.76E-06
ILMN_ .1738712 160897 GPR180 1.260 1.61E-15 -0.338 1.70E-04
ILMN_ .1738992 4332 MNDA 0.715 6.48E-10 -0.561 1.11E-07
ILMN_ .1739050 51268 PIPOX 0.262 6.17E-03 -0.324 1.80E-04
ILMN_ .1739297 8693 GALNT4 0.582 4.99E-08 -0.245 4.35E-03
ILMN_ .1739532 503645 DPRXP4 0.256 1.15E-02 -0.276 6.01E-03
ILMN_ .1739558 78987 CRELD1 0.592 1.55E-08 -0.467 1.63E-06
ILMN_ .1739576 51700 CYB5R2 0.963 5.68E-13 -0.500 5.21E-07
ILMN_ .1739622 4659 PPP1R12A 0.553 4.91E-07 -0.303 1.59E-03
ILMN_ .1739690 10886 NPFFR2 0.970 1.70E-12 -0.683 4.53E-09
ILMN_ .1739751 284129 SLC26A11 1.847 5.27E-18 -0.773 3.06E-09 ILMN_ .1739967 29110 TBK1 0.775 1.08E-11 -0.318 1.44E-04
ILMN_ 1740418 1594 CYP27B 1 0.429 3.55E-05 -0.318 1.28E-03
ILMN_ 1740493 7188 TRAF5 0.528 2.64E-06 -0.348 6.96E-04
ILMN_ .1740772 10307 APBB3 1.007 7.77E-13 -0.611 3.03E-08
ILMN_ .1740875 2358 FPR2 0.687 3.90E-08 -0.355 6.21E-04
ILMN_ .1740938 348 APOE 1.462 6.45E-17 -1.051 8.49E-14
ILMN_ .1741165 6556 SLC11A1 1.334 2.35E-17 -1.156 1.18E-15
ILMN_ .1741171 83877 TM2D2 0.418 3.71E-06 -0.388 1.67E-05
ILMN_ .1741507 440934 LOC440934 0.470 5.18E-06 -0.321 7.47E-04
ILMN_ .1742089 57486 NLN 0.896 3.43E-12 -0.474 1.58E-06
ILMN_ .1742332 115207 KCTD12 0.864 1.93E-10 -0.784 5.19E-10
ILMN_ .1742705 201266 SLC39A11 0.337 3.92E-04 -0.483 3.23E-06
ILMN_ .1742789 9404 LPXN 1.886 2.75E-20 -0.886 4.80E-12
ILMN_ .1742813 153339 TMEM167A 0.241 3.06E-03 -0.272 5.47E-04
ILMN_ .1742929 8820 HESX1 3.415 1.49E-27 -0.345 3.95E-05
ILMN_ .1743032 1520 CTSS 1.023 2.29E-12 -0.542 7.18E-07
ILMN_ .1743145 64167 ERAP2 0.973 2.85E-12 -0.322 5.40E-04
ILMN_ .1743199 1959 EGR2 3.483 5.64E-25 -0.271 6.31E-03
ILMN_ .1743316 144717 FAM109A 0.616 3.97E-08 -0.337 3.00E-04
ILMN_ .1743367 8322 FZD4 1.305 1.19E-14 -0.299 1.65E-03
ILMN_ .1743394 3174 HNF4G 0.255 2.71E-03 -0.422 1.20E-05
ILMN_ 1744046 1730 DIAPH2 0.490 1.00E-07 -0.653 4.84E-10
ILMN_ .1744212 3635 INPP5D 0.317 2.26E-03 -0.595 2.77E-07
ILMN_ .1744239 10116 FEMIB 0.977 4.84E-13 -0.409 1.16E-05
ILMN_ 1744604 1535 CYBA 0.373 1.13E-05 -0.288 4.00E-04
ILMN_ 1744963 30001 EROIL 0.442 7.71E-07 -0.326 8.97E-05
ILMN_ .1745034 4891 SLC11A2 2.407 1.42E-21 -0.639 6.37E-08
ILMN_ .1745110 9741 LAPTM4A 0.625 4.20E-08 -0.337 2.67E-04
ILMN_ .1745148 57169 ZNFX1 2.141 2.44E-22 -0.230 4.39E-03
ILMN_ .1745242 5359 PLSCR1 2.481 4.79E-22 -0.294 8.98E-04
ILMN_ .1745356 4283 CXCL9 1.266 8.90E-14 -1.119 8.62E-13
ILMN_ .1745368 23585 TMEM50A 0.482 1.24E-06 -0.342 1.28E-04
ILMN_ .1745607 2 A2M 1.904 2.59E-18 -1.396 1.11E-15
ILMN_ .1745798 2963 GTF2F2 0.524 1.34E-06 -0.300 1.84E-03
ILMN_ .1745954 23603 COROIC 0.320 8.17E-04 -0.594 1.95E-07
ILMN_ 1745994 8522 GAS7 1.507 7.39E-18 -1.243 1.07E-15
ILMN_ .1746085 3486 IGFBP3 5.708 1.10E-30 -2.043 4.73E-19
ILMN_ .1746135 79142 PHF23 0.218 1.18E-02 -0.621 9.14E-09
ILMN_ .1746148 375387 LRRC33 0.629 1.93E-09 -0.610 5.82E-09
ILMN_ .1746171 9555 H2AFY 0.540 1.32E-07 -0.580 3.85E-08
ILMN_ .1746578 9962 SLC23A2 0.344 3.06E-04 -0.234 6.28E-03
ILMN_ .1746633 203259 C9orf25 0.421 2.53E-06 -0.309 2.64E-04
ILMN_ .1746658 6096 RORB 0.779 2.63E-10 -0.305 7.88E-04
ILMN_ .1746836 5724 PTAFR 2.721 2.42E-23 -1.583 6.44E-18 ILMN_ 1746864 9595 PSCDBP 2.707 4.45E-23 -0.470 7.47E-06
ILMN_ .1746888 26577 PCOLCE2 0.961 5.33E-14 -0.487 1.97E-07
ILMN_ .1747305 155038 GIMAP8 2.330 1.78E-21 -2.069 2.84E-20
ILMN_ 1747344 3563 IL3RA 0.798 1.50E-10 -0.293 1.40E-03
ILMN_ 1747347 284021 C17orf60 1.173 2.22E-15 -0.961 2.81E-13
ILMN_ 1747744 10184 LHFPL2 2.348 9.75E-22 -1.180 9.79E-15
ILMN_ .1748281 5602 MAPK10 0.472 5.49E-05 -0.304 2.36E-03
ILMN_ .1748338 54329 GPR85 0.426 6.45E-05 -0.429 1.22E-05
ILMN_ 1748473 55303 GIMAP4 2.797 1.61E-22 -1.355 7.77E-15
ILMN_ .1748616 2962 GTF2F1 0.841 5.33E-10 -0.611 1.12E-07
ILMN_ .1748685 11074 TRIM31 1.926 6.40E-21 -0.449 2.01E-06
ILMN_ .1748797 2885 GRB2 0.545 8.69E-06 -0.869 1.07E-10
ILMN_ .1749011 55707 NECAP2 0.916 1.91E-13 -0.278 5.83E-04
ILMN_ .1749078 7077 TIMP2 0.440 7.36E-06 -0.282 8.66E-04
ILMN_ .1749109 5660 PSAP 1.852 2.43E-21 -0.212 5.13E-03
ILMN_ .1749150 59350 RXFP1 0.835 2.20E-11 -1.097 4.20E-15
ILMN_ .1749324 1807 DPYS 0.895 5.00E-11 -0.272 2.43E-03
ILMN_ .1749327 5603 MAPK13 0.655 3.86E-09 -0.498 6.48E-07
ILMN_ .1749722 57674 RNF213 0.790 1.58E-09 -0.639 4.35E-08
ILMN_ .1750101 6282 S100A11 0.871 1.68E-13 -0.270 4.92E-04
ILMN_ .1750178 653450 LOC653450 0.540 3.33E-07 -0.371 6.27E-05
ILMN_ .1750324 3488 IGFBP5 0.573 9.31E-07 -0.330 8.14E-04
ILMN_ .1750373 3730 KALI 0.854 1.33E-11 -0.853 1.62E-11
ILMN_ .1750400 55337 C19orf66 2.593 1.68E-25 -0.214 4.72E-03
ILMN_ .1750549 55361 PI4K2A 1.055 3.04E-13 -0.453 6.44E-06
ILMN_ .1750678 91937 TIMD4 0.874 4.36E-11 -0.652 1.88E-08
ILMN_ .1750689 64398 MPP5 0.281 9.76E-03 -0.502 8.12E-07
ILMN_ .1750693 6745 SSR1 0.404 4.08E-06 -0.247 1.99E-03
ILMN_ .1750805 257106 ARHGAP30 0.809 1.35E-11 -0.378 2.40E-05
ILMN_ .1750876 22950 SLC4A1AP 0.388 1.44E-04 -0.365 3.30E-04
ILMN_ .1750974 6280 S100A9 0.235 7.31E-03 -2.197 1.54E-21
ILMN_ .1751028 871 SERPINH1 0.599 4.85E-08 -0.692 4.21E-09
ILMN_ .1751079 6890 TAP1 2.956 1.27E-26 -0.409 3.37E-06
ILMN_ .1751195 653438 LOC653438 0.314 1.29E-04 -0.729 6.35E-11
ILMN_ .1751234 29071 C1GALT1C1 0.469 4.66E-06 -0.312 8.34E-04
ILMN_ .1751326 221303 FAM162B 2.820 2.12E-23 -0.905 4.14E-12
ILMN_ .1751789 3176 HNMT 1.192 9.67E-17 -0.327 5.40E-05
ILMN_ .1751868 200132 TCTEX1D1 1.269 3.87E-16 -0.908 1.82E-12
ILMN_ .1751886 9985 REC8 0.748 4.21E-10 -0.315 5.72E-04
ILMN_ .1751904 1910 EDNRB 1.765 3.97E-18 -0.302 1.58E-03
ILMN_ .1751941 728772 LOC728772 1.879 1.65E-21 -0.726 5.74E-11
ILMN_ .1752226 5032 P2RY11 0.705 2.50E-09 -0.624 2.24E-08
ILMN_ .1752281 23317 DNAJC13 0.249 3.17E-03 -0.241 4.81E-03
ILMN_ .1752355 219972 MPEG1 0.576 4.41E-07 -0.562 3.47E-07 ILMN_ .1752478 9249 DHRS3 1.729 7.88E-17 -0.518 3.15E-07
ILMN_ .1752526 255488 RNF144B 2.270 1.45E-20 -0.252 7.43E-03
ILMN_ .1752579 535 ATP6V0A1 0.968 3.42E-12 -0.317 7.34E-04
ILMN_ .1752592 3126 HLA-DRB4 0.803 8.10E-10 -0.418 6.72E-05
ILMN_ .1753312 84898 PLXDC2 1.400 2.40E-15 -0.701 9.05E-09
ILMN_ .1753468 967 CD63 0.470 4.26E-07 -0.622 2.82E-09
ILMN_ .1753607 56902 PNOl 0.207 3.93E-03 -0.326 5.50E-05
ILMN_ .1753758 246778 IL27 1.022 1.92E-11 -0.472 2.57E-05
ILMN_ .1753933 389658 FAM150A 1.139 3.87E-15 -0.365 4.03E-05
ILMN_ .1754315 166785 MMAA 0.645 2.94E-08 -0.351 2.39E-04
ILMN_ .1755024 9641 IKBKE 1.925 9.98E-20 -0.805 1.28E-10
ILMN_ .1755369 5864 RAB3A 0.274 2.69E-03 -0.299 5.32E-04
ILMN_ .1755537 9086 EIF1AY 0.571 1.52E-07 -0.390 5.86E-05
ILMN_ .1755643 11320 MGAT4A 0.620 1.73E-08 -0.889 3.97E-12
ILMN_ .1755732 80210 ARMC9 0.511 4.02E-07 -0.255 2.30E-03
ILMN_ .1756417 353322 ANKRD37 0.610 2.49E-08 -0.240 5.08E-03
ILMN_ .1756595 54436 SH3TC1 1.847 3.68E-19 -0.890 1.20E-12
ILMN_ .1756793 11044 POLS 1.200 2.39E-15 -0.497 6.34E-07
ILMN_ .1756806 4170 MCL1 1.730 7.92E-19 -0.295 9.02E-04
ILMN_ .1756860 9352 TXNL1 0.302 3.20E-03 -0.279 5.65E-03
ILMN_ .1756862 80833 APOL3 2.272 8.05E-22 -0.457 3.43E-06
ILMN_ .1756992 4582 MUC1 0.950 l.lOE-10 -1.985 4.29E-20
ILMN_ .1757186 170575 GIMAP1 0.953 1.76E-10 -0.566 2.80E-06
ILMN_ .1757210 91860 CALML4 0.376 7.52E-06 -0.869 5.24E-13
ILMN_ .1757406 3006 HIST1H1C 0.483 2.27E-06 -0.496 6.18E-07
ILMN_ .1757467 3005 H1F0 0.735 2.89E-11 -0.335 6.60E-05
ILMN_ .1757794 254065 BRWD3 0.272 3.22E-03 -0.368 1.28E-04
ILMN_ .1757827 81552 ECOP 1.457 1.26E-17 -0.716 4.09E-10
DKFZp761P042
ILMN_ .1757872 157285 0.404 8.31E-06 -0.239 3.39E-03
3
ILMN_ .1758146 140885 SIRPA 1.491 8.35E-18 -0.543 1.02E-07
ILMN_ .1758315 285195 SLC9A9 1.246 1.27E-15 -0.253 2.80E-03
ILMN_ .1758400 116443 GRIN3A 1.228 1.24E-14 -0.670 8.22E-09
ILMN_ .1758418 10673 TNFSF13B 2.888 2.69E-25 -0.612 3.62E-09
ILMN_ .1758831 55072 RNF31 0.294 1.58E-03 -0.381 9.26E-05
ILMN_ .1758938 1318 SLC31A2 2.246 5.20E-20 -0.665 7.48E-08
ILMN_ .1758963 65220 NADK 1.350 9.03E-16 -0.403 4.49E-05
ILMN_ .1759097 10962 MLLT11 0.586 1.88E-06 -0.363 1.64E-04
ILMN_ .1759325 283951 C16orf91 0.370 1.90E-05 -0.380 1.99E-05
ILMN_ .1759341 4125 MAN2B1 0.296 1.04E-03 -0.528 6.15E-07
ILMN_ .1759787 7056 THBD 1.877 9.95E-20 -3.286 4.20E-27
ILMN_ .1760027 7454 WAS 0.304 4.19E-04 -0.488 3.56E-07
ILMN_ .1760133 440607 LOC440607 0.355 3.24E-04 -0.250 7.39E-03
ILMN_ .1760718 83637 ZMIZ2 1.318 7.18E-15 -0.280 2.62E-03 ILMN_ .1760741 4704 NDUFA9 0.320 6.26E-04 -0.376 1.02E-04
ILMN_ .1760778 2022 ENG 1.381 4.99E-17 -0.615 6.55E-09
ILMN_ .1761058 84129 ACAD 11 0.712 7.82E-08 -0.304 4.20E-03
ILMN_ .1761072 653631 LOC653631 0.683 1.19E-08 -0.348 2.15E-04
ILMN_ .1761387 648998 LOC648998 0.619 5.76E-09 -0.407 1.09E-05
ILMN_ .1761463 79180 EFHD2 0.346 5.33E-05 -0.428 3.85E-06
ILMN_ .1761793 8542 APOL1 0.892 9.01E-11 -0.389 1.59E-04
ILMN_ .1761829 3098 HK1 1.365 2.14E-15 -0.571 2.82E-07
ILMN_ .1761921 3595 IL12RB2 0.503 6.94E-07 -0.341 7.32E-05
ILMN_ .1761941 51313 C4orfl8 1.012 2.49E-13 -0.766 1.99E-10
ILMN_ .1762106 4313 MMP2 0.809 1.89E-10 -0.589 9.61E-08
ILMN_ .1762260 718 C3 1.270 4.04E-15 -0.521 1.77E-07
ILMN_ .1762594 64127 NOD2 1.458 4.39E-17 -0.485 6.31E-07
ILMN_ .1763000 55803 ADAP2 2.934 1.49E-25 -1.063 5.90E-14
ILMN_ .1763003 643002 LOC643002 0.306 7.87E-04 -0.299 1.22E-03
ILMN_ .1763007 64645 HIAT1 0.906 9.79E-12 -0.378 5.88E-05
ILMN_ .1763198 6778 STAT6 0.934 2.57E-13 -0.266 8.35E-04
ILMN_ .1763200 9666 DZIP3 0.297 2.32E-03 -0.261 6.48E-03
ILMN_ .1763322 1232 CCR3 0.385 3.94E-04 -0.409 5.50E-05
ILMN_ .1763487 1493 CTLA4 0.250 2.43E-03 -0.250 2.61E-03
ILMN_ .1763523 3035 HARS 0.245 1.05E-03 -0.347 3.00E-05
ILMN_ .1763637 9711 KIAA0226 1.467 4.43E-17 -0.452 1.75E-06
ILMN_ .1763763 11035 RIPK3 0.472 6.33E-07 -0.461 8.65E-07
ILMN_ .1763828 4520 MTF1 1.755 2.38E-20 -0.438 1.48E-06
ILMN_ .1764455 653520 LOC653520 0.286 6.40E-03 -0.329 2.02E-03
ILMN_ 1764489 26608 TBL2 1.641 1.23E-18 -0.830 2.72E-11
ILMN_ .1764571 57636 ARHGAP23 0.384 6.46E-06 -0.219 5.04E-03
ILMN_ .1764709 9935 MAFB 5.348 1.94E-31 -0.458 4.93E-06
ILMN_ .1764723 285590 SH3PXD2B 2.015 4.18E-20 -0.971 1.44E-12
ILMN_ .1764788 7133 TNFRSF1B 1.514 1.37E-17 -0.699 1.11E-09
ILMN_ .1764801 285047 LOC285047 1.937 4.10E-20 -0.934 3.53E-12
ILMN_ 1764964 3460 IFNGR2 2.376 8.83E-23 -0.498 8.62E-07
ILMN_ .1765547 3660 IRF2 1.624 4.10E-18 -0.726 2.37E-10
ILMN_ .1765557 25903 OLFML2B 1.423 1.05E-17 -1.367 1.07E-17
ILMN_ .1765574 7020 TFAP2A 1.720 1.91E-16 -1.778 1.30E-17
ILMN_ .1765641 10371 SEMA3A 0.340 4.90E-04 -0.394 9.37E-05
ILMN_ .1765994 81030 ZBP1 0.852 5.02E-12 -0.351 6.95E-05
ILMN_ .1766054 19 ABCA1 1.315 6.01E-17 -0.750 5.23E-11
ILMN_ .1766079 6819 SULT1C2 0.455 8.58E-06 -0.386 5.10E-05
ILMN_ .1766184 654346 LOC654346 1.134 4.00E-13 -0.710 3.63E-09
ILMN_ .1766637 2717 GLA 0.813 8.62E-12 -0.329 1.08E-04
ILMN_ .1766832 653463 LOC653463 0.244 8.23E-03 -0.274 3.50E-03
ILMN_ .1767142 54816 ZNF280D 0.238 2.69E-03 -0.373 2.83E-05
ILMN_ .1767360 3588 IL10RB 0.591 1.34E-06 -0.511 5.51E-06 DNAJC25-
ILMN_ .1767809 552891 0.351 3.20E-03 -0.389 2.49E-04
GNG10
ILMN_ .1767810 642639 LOC642639 1.171 1.39E-11 -0.853 1.32E-10
ILMN_ .1767929 642252 LOC642252 1.103 1.83E-14 -0.332 1.62E-04
ILMN_ .1768282 90203 SNX21 0.332 4.59E-04 -0.312 9.55E-04
ILMN_ .1768391 10123 ARL4C 0.299 2.39E-03 -0.331 8.92E-04
ILMN_ .1768394 10092 ARPC5 0.342 1.54E-04 -0.423 6.32E-06
ILMN_ .1768553 283050 LOC283050 1.771 3.33E-15 -1.024 2.57E-10
ILMN_ .1768598 3903 LAIR1 0.859 7.29E-12 -0.717 6.15E-10
ILMN_ .1768812 53826 FXYD6 1.547 1.11E-17 -0.862 1.84E-11
ILMN_ .1768870 830 CAPZA2 0.322 1.20E-04 -0.362 3.86E-05
ILMN_ .1768940 1306 COL15A1 1.155 1.11E-12 -0.692 3.38E-08
ILMN_ .1768973 8338 HIST2H2AC 1.266 3.10E-15 -0.334 2.29E-04
ILMN_ .1769040 10499 NCOA2 1.211 4.77E-14 -0.332 1.12E-04
ILMN_ .1769229 597 BCL2A1 0.793 4.86E-09 -0.272 8.10E-03
ILMN_ .1769245 11010 GLIPR1 0.699 3.47E-09 -1.193 7.81E-15
ILMN_ .1769264 64087 MCCC2 0.269 2.07E-03 -0.377 4.98E-05
ILMN_ .1769383 55340 GIMAP5 1.859 1.26E-20 -1.419 1.60E-18
ILMN_ .1769433 10788 IQGAP2 0.717 9.81E-09 -0.374 1.76E-04
ILMN_ .1769503 223082 ZNRF2 0.679 1.81E-08 -0.380 1.86E-04
ILMN_ .1769546 54453 RIN2 4.126 1.74E-26 -0.784 1.49E-09
ILMN_ .1769665 5878 RAB5C 0.348 1.06E-03 -0.576 1.03E-06
ILMN_ .1769734 51251 NT5C3 2.356 7.62E-22 -0.497 1.82E-06
ILMN_ .1769787 83642 SELO 0.753 6.22E-09 -0.606 2.60E-07
ILMN_ .1769810 10550 ARL6IP5 0.347 4.42E-05 -0.311 1.84E-04
ILMN_ .1769876 55357 TBC1D2 2.742 1.67E-23 -0.756 6.48E-10
ILMN_ .1769988 3446 IFNA10 1.593 4.43E-17 -0.269 4.67E-03
ILMN_ .1771333 961 CD47 0.444 2.53E-05 -0.529 2.08E-06
ILMN_ .1771385 115361 GBP4 4.157 1.19E-29 -0.377 3.64E-05
ILMN_ .1771627 57178 ZMIZ1 1.307 1.63E-16 -0.506 1.13E-07
ILMN_ .1771664 26253 CLEC4E 0.308 2.56E-03 -0.305 1.81E-03
ILMN_ .1771841 8061 FOSL1 0.462 5.84E-06 -0.364 1.82E-04
ILMN_ .1771862 51061 TXNDC11 0.336 6.97E-05 -0.327 1.24E-04
ILMN_ .1771921 150274 HSCB 0.926 1.45E-11 -0.272 2.91E-03
ILMN_ .1772131 7850 IL1R2 1.908 4.57E-18 -1.981 1.34E-20
ILMN_ .1772189 215 ABCD1 0.529 1.25E-07 -0.570 4.63E-08
ILMN_ .1772218 3113 HLA-DPA1 0.867 2.06E-11 -0.720 9.32E-10
ILMN_ .1772312 56033 BARX1 0.506 6.52E-08 -0.690 1.63E-10
ILMN_ .1772359 7805 LAPTM5 0.768 6.16E-09 -0.625 3.40E-07
ILMN_ .1772387 7097 TLR2 1.103 9.45E-11 -0.425 5.27E-04
ILMN_ .1772686 89846 FGD3 0.347 7.98E-05 -0.460 1.68E-06
ILMN_ .1772964 6355 CCL8 8.375 7.49E-34 -2.916 8.23E-24
ILMN_ .1773125 953 ENTPD1 0.372 6.11E-05 -0.669 4.75E-09
ILMN_ .1773363 4261 CIITA 0.361 2.16E-04 -0.361 2.49E-04 ILMN_ .1773681 9629 CLCA3 1.352 1.30E-14 -1.187 8.72E-14
ILMN_ .1773865 3309 HSPA5 0.331 6.15E-05 -0.477 4.13E-07
ILMN_ .1773935 55858 TMEM165 0.306 3.08E-04 -0.775 5.62E-11
ILMN_ .1773963 2769 GNA15 0.992 2.21E-14 -1.256 1.04E-16
ILMN_ .1774077 2634 GBP2 4.333 1.00E-28 -0.684 8.16E-09
ILMN_ .1774211 643853 FLJ45032 0.264 2.54E-03 -0.456 3.47E-06
ILMN_ .1774287 629 CFB 2.423 1.91E-23 -0.773 1.98E-11
ILMN_ 1774447 272 AMPD3 1.803 1.89E-17 -0.803 2.52E-09
ILMN_ 1774604 25953 PNKD 3.394 3.05E-27 -1.248 9.88E-16
ILMN_ .1774739 4323 MMP14 0.633 5.63E-06 -0.462 3.40E-04
ILMN_ 1774874 3557 IL1RN 4.848 2.26E-31 -1.635 2.71E-19
ILMN_ .1775501 3553 IL1B 6.055 7.28E-30 -2.029 4.16E-18
ILMN_ .1775708 6515 SLC2A3 1.932 3.97E-20 -0.471 2.26E-06
ILMN_ .1776047 646197 LOC646197 0.374 2.95E-03 -0.968 7.23E-10
ILMN_ .1776157 5414 Sep-04 1.417 2.32E-17 -0.339 1.08E-04
ILMN_ .1776337 26973 CHORDC1 0.318 4.20E-04 -0.545 4.89E-08
ILMN_ .1776778 165631 PARP15 0.542 3.17E-06 -0.308 1.82E-03
ILMN_ .1777260 222255 ATXN7L1 1.280 1.48E-15 -0.338 1.91E-04
ILMN_ .1777299 652771 LOC652771 0.525 3.69E-06 -0.400 6.46E-05
ILMN_ .1777366 9694 TTC35 0.230 1.01E-02 -0.244 6.79E-03
ILMN_ .1777519 3695 ITGB7 1.129 4.01E-13 -0.336 4.92E-04
ILMN_ .1777584 3735 KARS 0.392 2.94E-05 -0.304 6.64E-04
ILMN_ .1777998 9938 ARHGAP25 1.653 2.91E-18 -0.263 2.78E-03
ILMN_ .1778371 56267 CCBL2 0.428 3.16E-06 -0.447 2.23E-06
ILMN_ .1778523 687 KLF9 0.521 4.18E-07 -0.502 7.45E-07
ILMN_ .1778611 2631 GBAS 0.461 1.03E-05 -0.568 3.55E-07
ILMN_ .1778650 50853 VILL 0.232 6.81E-03 -0.344 1.55E-04
ILMN_ .1778668 6876 TAGLN 0.257 2.38E-03 -0.376 2.61E-05
ILMN_ .1778977 7305 TYROBP 0.998 1.63E-13 -0.291 6.29E-04
ILMN_ .1778985 90826 PRMT10 0.284 1.63E-03 -0.254 4.69E-03
ILMN_ .1779076 135114 HINT3 0.989 2.50E-12 -0.720 3.42E-09
ILMN_ .1779252 10346 TRIM22 3.405 1.03E-27 -0.260 9.22E-04
ILMN_ .1779492 57154 SMURF1 0.416 7.82E-06 -0.255 2.36E-03
ILMN_ .1779674 5793 PTPRG 0.700 4.97E-08 -0.738 9.09E-09
ILMN_ .1780057 5973 RENBP 1.233 5.22E-16 -0.515 2.03E-07
ILMN_ .1780197 57465 TBC1D24 0.637 5.32E-07 -0.276 7.18E-03
ILMN_ .1780546 5008 OSM 2.100 2.34E-18 -0.492 4.22E-05
ILMN_ .1780799 5168 ENPP2 3.872 4.98E-28 -2.289 2.59E-22
ILMN_ .1780861 653506 LOC653506 1.677 3.67E-19 -0.218 6.70E-03
ILMN_ .1781010 50650 ARHGEF3 2.255 7.22E-24 -0.535 1.63E-08
ILMN_ .1781155 4067 LYN 2.042 6.53E-21 -0.278 8.64E-04
ILMN_ .1781580 25798 BRI3 1.222 7.06E-15 -0.337 2.99E-04
ILMN_ .1781761 22875 ENPP4 1.168 2.53E-14 -0.499 1.73E-06
ILMN_ .1781812 8013 NR4A3 0.878 5.67E-11 -0.492 3.82E-06 ILMN_ .1781999 10061 ABCF2 0.337 7.42E-05 -0.515 3.67E-08
ILMN_ .1782222 23325 KIAA1033 1.090 3.05E-11 -0.409 4.50E-05
ILMN_ .1782295 7223 TRPC4 0.333 6.50E-04 -0.282 1.35E-03
ILMN_ .1782419 2791 GNG11 0.317 9.44E-03 -0.303 3.03E-03
ILMN_ .1782487 400759 LOC400759 3.223 7.26E-25 -0.872 6.43E-11
ILMN_ .1782551 1875 E2F5 0.363 2.84E-05 -0.373 2.17E-05
ILMN_ .1782679 57491 AHRR 0.754 2.44E-10 -0.871 1.39E-12
ILMN_ .1782938 117247 SLC16A10 1.699 3.00E-17 -0.768 3.46E-09
ILMN_ .1783156 650832 LOC650832 1.034 2.41E-14 -0.222 4.56E-03
ILMN_ .1783593 6357 CCL13 1.807 3.03E-19 -0.901 9.53E-12
ILMN_ .1783621 129607 CMPK2 2.713 1.32E-22 -0.418 4.69E-05
ILMN_ .1783843 60672 ΜΠΡ 0.208 1.20E-02 -0.831 3.35E-11
ILMN_ .1784005 644615 LOC644615 1.469 1.38E-16 -0.442 1.41E-05
ILMN_ 1784046 8847 DLEU2 0.971 4.24E-13 -0.905 2.63E-12
ILMN_ .1784105 55238 SLC38A7 0.952 7.42E-11 -0.456 4.22E-05
ILMN_ .1784320 9844 ELMOl 0.506 1.97E-07 -0.302 2.60E-04
ILMN_ .1784863 948 CD36 2.346 4.96E-23 -0.368 5.18E-05
ILMN_ 1784884 11025 LILRB3 3.821 3.73E-28 -1.568 7.31E-18
ILMN_ 1784948 90853 SPOCD1 0.307 2.92E-03 -0.387 3.21E-04
ILMN_ .1785005 4689 NCF4 0.385 1.86E-05 -0.865 5.18E-12
ILMN_ .1785037 6746 SSR2 0.263 3.78E-03 -0.239 8.13E-03
ILMN_ .1785060 81619 TSPAN14 0.773 9.90E-11 -0.648 5.43E-09
ILMN_ .1785158 64224 HERPUD2 0.850 9.76E-10 -0.476 1.55E-05
ILMN_ .1785202 6775 STAT4 2.521 1.06E-20 -0.439 5.57E-05
ILMN_ .1785345 53831 GPR84 3.169 1.08E-26 -1.157 2.04E-15
ILMN_ .1785402 4052 LTBP1 0.295 5.57E-03 -0.275 5.87E-03
ILMN_ .1785902 714 C1QC 0.653 2.91E-07 -0.528 6.16E-06
ILMN_ .1786211 8925 HERC1 0.717 9.80E-12 -0.286 2.04E-04
ILMN_ .1786347 3842 TNPOl 0.684 4.46E-08 -0.350 4.59E-04
ILMN_ .1786353 1259 CNGA1 0.494 1.43E-04 -0.343 4.85E-03
ILMN_ .1786357 116985 CENTD2 0.805 8.87E-10 -0.432 3.77E-05
ILMN_ .1786426 79713 TMEM149 0.410 8.44E-06 -0.462 1.55E-06
ILMN_ .1786429 10161 P2RY5 2.404 1.04E-21 -1.126 1.16E-14
ILMN_ .1786612 5721 PSME2 0.893 6.72E-13 -0.410 4.69E-06
ILMN_ .1786722 25946 ZNF385A 0.457 1.59E-05 -0.768 1.95E-09
ILMN_ .1787370 55471 C2orf56 0.448 4.82E-06 -0.267 5.00E-04
ILMN_ .1787461 864 RUNX3 0.741 1.71E-10 -0.571 5.30E-08
ILMN_ .1787529 719 C3AR1 2.673 4.05E-24 -0.371 6.36E-05
ILMN_ .1787897 2919 CXCL1 2.049 2.32E-16 -0.504 7.27E-05
ILMN_ .1788019 3908 LAMA2 0.263 3.25E-03 -0.232 6.10E-03
ILMN_ .1788062 6455 SH3GL1 0.444 8.87E-06 -0.335 3.60E-04
ILMN_ .1788180 5872 RAB13 1.514 8.74E-16 -0.272 5.90E-03
ILMN_ .1788347 85457 KIAA1737 0.499 1.46E-07 -0.404 7.55E-06
ILMN_ .1789007 341 APOC1 1.476 2.93E-14 -1.054 3.23E-11 ILMN_ .1789074 3303 HSPA1A 0.505 4.21E-05 -0.431 1.94E-04
ILMN_ .1789095 659 BMPR2 0.858 5.66E-12 -0.449 2.93E-06
ILMN_ .1789361 9033 PKD2L1 1.300 1.27E-16 -0.241 2.59E-03
ILMN_ .1789599 4681 NBL1 1.436 1.07E-16 -1.025 4.18E-13
ILMN_ .1789642 80331 DNAJC5 1.061 5.21E-14 -0.599 8.83E-09
ILMN_ .1790311 10484 SEC23A 0.513 2.97E-05 -0.290 7.50E-03
ILMN_ .1790529 4060 LUM 1.247 3.89E-13 -1.224 3.69E-13
ILMN_ .1790562 2140 EYA3 0.269 1.14E-02 -0.654 2.75E-07
ILMN_ .1790659 26354 GNL3 0.286 2.93E-03 -0.443 1.06E-06
ILMN_ .1790692 10578 GNLY 0.986 1.13E-11 -1.064 1.66E-12
ILMN_ .1790973 8760 CDS2 0.973 2.34E-13 -0.278 1.07E-03
ILMN_ .1791057 3455 IFNAR2 1.199 1.66E-14 -0.615 1.18E-08
ILMN_ .1791162 440137 FLJ31945 0.230 7.98E-03 -0.318 5.52E-04
ILMN_ .1791186 93663 ARHGAP18 0.732 l.OlE-10 -0.511 1.81E-07
ILMN_ .1791575 92906 HNRPLL 0.588 1.53E-07 -0.383 1.11E-04
ILMN_ .1791754 1375 CPT1B 0.340 1.62E-03 -0.637 4.16E-07
ILMN_ .1791847 23604 DAPK2 1.046 7.45E-14 -0.511 4.18E-07
ILMN_ .1791912 51092 SIDT2 0.693 9.35E-10 -0.432 5.49E-06
ILMN_ .1792076 55809 TRERF1 0.340 3.23E-04 -0.609 2.09E-08
ILMN_ .1792489 10109 ARPC2 0.215 5.21E-03 -0.315 1.99E-04
ILMN_ .1792679 3678 ITGA5 0.788 8.43E-10 -0.680 1.17E-08
ILMN_ .1792885 1075 CTSC 1.635 7.82E-20 -1.113 2.38E-15
ILMN_ .1792997 27020 NPTN 0.539 4.76E-07 -0.408 1.87E-05
ILMN_ .1793220 2618 GART 0.314 3.49E-03 -0.461 6.07E-05
ILMN_ .1793241 6715 SRD5A1 1.261 2.75E-14 -0.548 9.59E-07
ILMN_ .1793517 8437 RASAL1 0.234 7.91E-03 -0.290 4.34E-04
ILMN_ .1793672 147912 SIX5 0.342 1.52E-04 -0.303 3.45E-04
ILMN_ .1793959 83440 ADPGK 0.492 4.00E-08 -0.309 7.28E-05
ILMN_ .1794011 9435 CHST2 0.903 1.85E-08 -0.446 5.88E-04
ILMN_ .1794056 25822 DNAJB5 0.468 3.62E-05 -0.350 1.61E-04
ILMN_ .1794392 1654 DDX3X 0.281 9.06E-04 -0.535 1.24E-07
ILMN_ 1794442 84627 ZNF469 0.295 1.09E-03 -0.324 3.95E-04
ILMN_ 1794643 84619 ZGPAT 0.253 1.42E-03 -0.227 4.54E-03
ILMN_ 1794914 80019 UBTD1 0.444 2.71E-06 -0.251 3.24E-03
ILMN_ .1794950 57529 RGAG1 0.655 6.08E-10 -0.519 1.05E-07
ILMN_ .1794967 56478 EIF4ENIF1 0.199 6.38E-03 -0.265 6.33E-04
ILMN_ .1795055 81543 LRRC3 0.625 2.66E-09 -0.433 2.11E-06
ILMN_ .1795170 84631 SLITRK2 0.704 8.62E-10 -0.335 2.30E-04
ILMN_ .1795564 144097 Cl lorf84 0.343 7.44E-04 -0.295 3.08E-03
ILMN_ .1795778 8974 P4HA2 0.748 9.68E-10 -0.464 4.40E-06
ILMN_ .1795826 9114 ATP6V0D1 0.651 6.98E-07 -0.319 2.56E-03
ILMN_ .1795918 116988 CENTG3 1.113 6.13E-15 -0.570 2.41E-08
ILMN_ .1795991 51493 C22orf28 1.048 8.03E-15 -0.520 6.72E-08
ILMN_ .1796179 85236 HIST1H2BK 1.380 2.14E-15 -0.683 1.87E-08 971 ILMN_ .1796316 4318 MMP9 3.242 6.86E-26 -2.774 2.51E-24
972 ILMN_ .1796335 54947 LPCAT2 0.603 8.79E-09 -0.643 1.48E-09
973 ILMN_ .1796336 55201 MAP IS 0.620 4.08E-09 -0.245 2.29E-03
974 ILMN_ .1796349 10924 SMPDL3A 1.602 7.84E-18 -0.450 4.09E-06
975 ILMN_ .1796409 713 C1QB 0.801 l.lOE-10 -0.458 3.78E-06
976 ILMN_ .1796490 2907 GRINA 1.708 5.69E-20 -0.291 4.70E-04
977 ILMN_ .1796537 2533 FYB 1.510 5.26E-17 -0.401 4.42E-05
978 ILMN_ .1796639 50613 UBQLN3 0.263 4.13E-03 -0.303 9.68E-04
979 ILMN_ .1796642 4688 NCF2 1.035 9.77E-14 -1.108 1.37E-14
980 ILMN_ .1797359 117852 TRIM78P 1.068 4.53E-13 -0.565 1.93E-07
981 ILMN_ .1797531 51422 PRKAG2 1.345 4.24E-17 -0.279 5.71E-04
982 ILMN_ .1797735 81563 Clorf21 0.974 2.40E-12 -0.477 3.51E-06
983 ILMN_ .1797895 2867 FFAR2 0.905 2.05E-10 -0.476 2.04E-05
984 ILMN_ .1798061 23503 ZFYVE26 1.331 2.72E-16 -0.476 1.56E-06
985 ILMN_ .1798256 7378 UPP1 2.267 1.29E-20 -0.373 2.51E-04
986 ILMN_ .1798372 305 ANXA2P3 0.604 5.52E-07 -0.301 1.91E-03
987 ILMN_ .1798459 56342 PPAN 0.279 4.51E-03 -0.545 1.80E-06
988 ILMN_ .1798475 1439 CSF2RB 0.414 3.02E-05 -0.240 5.73E-03
989 ILMN_ .1798612 124460 SNX20 0.407 1.11E-03 -0.441 2.25E-04
990 ILMN_ .1798706 1880 EBI2 2.060 2.88E-20 -2.996 2.80E-25
991 ILMN_ .1798712 7375 USP4 0.537 2.68E-08 -0.494 1.65E-07
992 ILMN_ .1798980 832 CAPZB 0.396 2.08E-04 -0.691 2.63E-08
993 ILMN_ .1799024 55697 VAC 14 0.599 9.91E-09 -0.290 6.40E-04
994 ILMN_ .1799467 219285 SAMD9L 2.346 7.42E-23 -0.338 1.63E-04
995 ILMN_ .1799487 90634 N4BP2L1 1.107 1.25E-13 -0.294 9.22E-04
996 ILMN_ .1799600 9754 STARD8 0.267 2.79E-03 -0.359 1.83E-04
997 ILMN_ .1800787 23180 RFTN1 1.706 1.25E-17 -0.276 4.14E-03
998 ILMN_ .1800952 5717 PSMD11 0.352 1.65E-04 -0.320 4.61E-04
999 ILMN_ .1801205 10457 GPNMB 2.941 7.15E-24 -1.124 4.07E-13
1000 ILMN_ .1801307 8743 TNFSF10 4.130 3.74E-29 -1.195 3.93E-15
1001 ILMN_ .1801616 2012 EMP1 2.756 4.57E-25 -0.683 9.57E-10
1002 ILMN_ .1801710 54518 APBB1IP 0.460 4.34E-06 -0.251 4.60E-03
1003 ILMN_ .1802380 473 RERE 0.497 2.56E-07 -0.250 1.76E-03
1004 ILMN_ .1802649 10944 Cl lorf58 0.326 2.22E-04 -0.369 6.87E-05
1005 ILMN_ .1802923 344 APOC2 0.514 1.03E-06 -0.589 1.25E-07
1006 ILMN_ .1802971 64760 FAM160B2 0.199 1.22E-02 -0.224 6.36E-03
1007 ILMN_ .1803256 56977 STOX2 1.329 3.37E-17 -0.412 4.42E-06
1008 ILMN_ .1803277 9961 MVP 1.598 4.27E-18 -0.557 7.79E-08
1009 ILMN_ .1803318 8499 PPFIA2 0.630 2.00E-08 -0.432 1.40E-05
1010 ILMN_ .1803559 642477 FLJ39632 0.572 1.34E-08 -0.464 7.76E-07
1011 ILMN_ .1803560 7462 LAT2 0.237 3.96E-03 -0.750 2.02E-10
1012 ILMN_ .1803561 5321 PLA2G4A 0.376 1.97E-04 -0.251 8.57E-03
1013 ILMN_ .1803652 203197 C9orf91 2.047 1.86E-20 -0.361 6.84E-05
1014 ILMN_ .1803686 100 ADA 0.942 3.92E-13 -0.720 1.53E-10 1015 ILMN_ .1803745 6821 SUOX 0.335 5.69E-05 -0.313 1.34E-04
1016 ILMN_ .1803906 2116 ETV2 0.606 1.31E-06 -0.485 3.79E-05
1017 ILMN_ .1804051 29886 SNX8 0.567 1.10E-07 -0.368 6.99E-05
1018 ILMN_ .1804277 161742 SPRED1 0.974 7.19E-13 -0.398 2.85E-05
1019 ILMN_ 1804445 80063 ATF7IP2 0.245 3.74E-03 -0.264 2.51E-03
1020 ILMN_ .1804863 23307 FKBP15 1.221 3.71E-15 -0.805 2.46E-11
1021 ILMN_ .1804938 131601 GPR175 0.721 4.29E-10 -0.465 3.53E-07
1022 ILMN_ .1805098 5153 PDE1B 1.729 6.95E-18 -0.276 3.66E-03
1023 ILMN_ .1805228 116844 LRG1 0.544 7.68E-07 -0.576 2.27E-07
1024 ILMN_ .1805449 55080 TAPBPL 0.575 7.15E-08 -0.305 7.85E-04
1025 ILMN_ .1805737 5214 PFKP 0.221 5.37E-03 -0.297 4.79E-04
1026 ILMN_ .1805827 5464 PPA1 0.292 7.44E-04 -0.276 9.67E-04
1027 ILMN_ .1805863 124997 WDR81 0.724 7.43E-08 -0.535 2.56E-06
1028 ILMN_ .1806017 5720 PSME1 0.728 1.37E-11 -0.248 1.18E-03
1029 ILMN_ .1806165 3310 HSPA6 1.995 3.18E-17 -0.761 2.04E-08
1030 ILMN_ .1806275 113179 ADAT3 0.390 1.09E-05 -0.307 2.60E-04
1031 ILMN_ .1806365 649067 LOC649067 0.231 5.17E-03 -0.207 8.94E-03
1032 ILMN_ .1806790 6091 ROBOl 0.622 9.81E-08 -0.451 6.80E-06
1033 ILMN_ .1807114 255620 LOC255620 0.805 6.21E-10 -0.632 1.93E-08
1034 ILMN_ .1807277 10437 IFI30 3.090 9.01E-26 -0.745 9.68E-11
1035 ILMN_ 1807448 51439 FAM8A1 0.618 7.02E-09 -0.362 4.46E-05
1036 ILMN_ .1807533 55181 C17orf71 0.259 2.27E-03 -0.240 2.52E-03
1037 ILMN_ .1807662 3482 IGF2R 0.373 6.09E-05 -0.327 3.64E-04
1038 ILMN_ .1807825 9450 LY86 0.451 4.28E-07 -0.391 5.84E-06
1039 ILMN_ .1807873 58533 SNX6 0.774 1.27E-10 -0.337 1.41E-04
1040 ILMN_ .1807894 23428 SLC7A8 0.505 3.72E-06 -0.350 3.06E-04
1041 ILMN_ .1807919 7145 TNS1 0.589 4.16E-08 -0.526 4.39E-07
1042 ILMN_ .1808196 9446 GSTOl 0.912 8.39E-13 -0.359 4.04E-05
1043 ILMN_ .1808405 3117 HLA-DQA1 0.914 5.69E-10 -0.592 5.71E-07
1044 ILMN_ .1808715 389300 LOC389300 1.015 1.21E-13 -0.301 5.80E-04
1045 ILMN_ .1808811 22904 SBN02 0.490 1.93E-06 -0.416 2.29E-05
1046 ILMN_ .1809003 873 CBR1 0.914 1.91E-11 -0.411 4.28E-05
1047 ILMN_ .1809245 23760 PITPNB 0.309 2.21E-03 -0.280 5.12E-03
1048 ILMN_ .1809285 55802 DCP1A 1.495 1.44E-19 -0.373 6.22E-06
1049 ILMN_ .1809400 51571 FAM49B 0.295 7.46E-04 -0.661 5.17E-09
1050 ILMN_ .1809491 339184 CCDC144NL 0.502 5.46E-05 -0.335 2.26E-04
1051 ILMN_ .1809607 10105 PPIF 0.882 5.74E-10 -0.320 1.91E-03
1052 ILMN_ .1809751 192669 EIF2C3 0.426 1.49E-04 -0.333 1.32E-03
1053 ILMN_ .1809928 1292 COL6A2 0.569 1.41E-07 -0.238 6.69E-03
1054 ILMN_ .1809931 10397 NDRG1 1.261 2.60E-15 -0.366 7.00E-05
1055 ILMN_ .1810275 9056 SLC7A7 2.537 3.07E-22 -0.765 8.54E-11
1056 ILMN_ .1810608 87178 PNPT1 1.166 4.81E-14 -0.344 3.36E-04
1057 ILMN_ .1810836 8654 PDE5A 0.590 9.68E-08 -0.329 3.49E-04
1058 ILMN_ .1811114 10993 SDS 2.470 3.75E-23 -0.796 2.69E-11 1059 ILMN_ .1811171 29933 GPR132 2.351 3.72E-22 -0.619 1.74E-08
1060 ILMN_ ,1811364 130367 SGPP2 0.501 1.80E-05 -0.407 1.60E-04
1061 ILMN_ ,1811378 9567 GTPBP1 0.712 7.52E-10 -0.252 3.83E-03
1062 ILMN_ ,1811765 9509 ADAMTS2 0.363 6.74E-05 -0.682 1.55E-09
1063 ILMN_ ,1811823 81857 MED25 0.383 2.17E-05 -0.608 1.24E-08
1064 ILMN_ ,1812557 80279 CDK5RAP3 0.701 3.95E-10 -0.371 4.14E-05
1065 ILMN_ ,1812571 11021 RAB35 0.261 1.52E-03 -0.267 1.26E-03
1066 ILMN_ ,1812581 9604 RNF14 1.297 2.46E-13 -1.092 1.24E-11
1067 ILMN_ ,1812759 2643 GCH1 2.970 6.71E-24 -0.439 2.48E-05
1068 ILMN_ ,1812926 118429 ANTXR2 0.477 1.36E-07 -0.520 2.84E-08
1069 ILMN_ ,1813139 348094 ANKDD1A 0.718 3.76E-08 -0.230 6.99E-03
1070 ILMN_ ,1813338 3902 LAG3 2.260 6.98E-20 -1.060 3.22E-12
1071 ILMN_ ,1813374 126321 C19orf28 1.182 8.54E-15 -0.419 1.39E-05
1072 ILMN_ ,1813641 54863 C9orfl67 0.532 2.58E-07 -0.410 2.26E-05
1073 ILMN_ ,1813669 23294 ANKS1A 0.616 2.48E-09 -0.365 2.44E-05
1074 ILMN_ ,1813685 8934 RAB7L1 0.909 1.01E-13 -0.560 7.66E-09
1075 ILMN_ ,1814022 10062 NR1H3 1.659 9.33E-18 -0.526 5.48E-07
1076 ILMN_ ,1814194 6925 TCF4 2.001 5.64E-20 -0.825 5.79E-11
1077 ILMN_ ,1814221 4884 NPTX1 1.608 1.50E-17 -2.248 8.20E-22
1078 ILMN_ ,1814737 4012 LNPEP 0.838 6.23E-12 -0.534 1.03E-07
1079 ILMN_ ,1815261 9601 PDIA4 0.624 6.36E-07 -0.696 2.43E-08
1080 ILMN_ ,1815264 25807 RHBDD3 0.607 3.95E-08 -0.294 1.18E-03
1081 ILMN_ ,1815668 2970 GTF2IP1 0.803 7.27E-11 -0.523 3.09E-07
1082 ILMN_ ,1838319 730249 LOC730249 0.704 1.65E-07 -0.597 5.36E-07
1083 ILMN_ ,1893555 2.774 1.89E-24 -1.839 1.02E-19
1084 ILMN_ ,2041101 303 ANXA2P1 0.989 1.35E-10 -0.376 7.23E-04
1085 ILMN_ ,2041293 6713 SQLE 0.916 3.10E-12 -0.263 2.36E-03
1086 ILMN_ ,2041788 5358 PLS3 0.351 8.40E-05 -0.299 4.08E-04
1087 ILMN_ ,2043126 389903 CSAG3A 0.480 6.35E-05 -0.494 5.32E-06
1088 ILMN_ ,2048507 51274 KLF3 1.452 9.61E-14 -0.334 2.53E-03
1089 ILMN_ ,2048636 4200 ME2 0.370 1.79E-05 -0.418 2.48E-06
1090 ILMN_ ,2049536 51393 TRPV2 0.434 1.05E-05 -0.717 1.26E-09
1091 ILMN_ ,2049766 9603 NFE2L3 2.516 5.37E-25 -0.942 1.13E-13
1092 ILMN_ ,2052163 54432 YIPF1 0.670 5.05E-10 -0.363 3.73E-05
1093 ILMN_ ,2053415 3949 LDLR 0.390 6.54E-05 -0.408 4.88E-05
1094 ILMN_ ,2053829 643866 CBLN3 1.841 9.21E-19 -0.826 8.67E-11
1095 ILMN_ ,2056795 8287 USP9Y 0.349 5.83E-05 -0.324 1.94E-04
1096 ILMN_ ,2058512 5683 PSMA2 0.417 2.13E-05 -0.617 2.19E-08
1097 ILMN_ ,2058782 3429 IFI27 4.147 2.86E-30 -0.760 4.51E-11
1098 ILMN_ ,2062370 55035 NOL8 0.317 1.23E-03 -0.386 5.91E-05
1099 ILMN_ ,2062754 10011 SRA1 0.588 5.87E-08 -0.319 3.89E-04
1100 ILMN_ ,2063925 56259 CTNNBL1 0.670 7.72E-10 -0.429 4.35E-06
1101 ILMN_ ,2064725 196410 METTL7B 1.365 1.71E-15 -1.973 7.38E-20
1102 ILMN_ ,2065690 65983 GRAMD3 0.412 1.93E-05 -0.393 1.82E-05 1103 ILMN .2066066 3128 HLA-DRB6 0.921 5.14E-12 -0.495 3.94E-07
1104 ILMN .2066849 441168 FAM26F 1.107 4.96E-12 -0.535 1.73E-07
1105 ILMN .2067852 7779 SLC30A1 0.853 2.88E-12 -0.335 7.86E-05
1106 ILMN .2067890 6373 CXCL11 0.605 4.03E-08 -0.271 2.83E-03
1107 ILMN .2070044 152926 PPM IK 2.052 1.13E-18 -0.602 6.01E-08
1108 ILMN .2073289 9788 MTSS1 3.142 2.00E-24 -0.363 2.71E-04
1109 ILMN .2075440 171423 PDIA3P 0.361 1.94E-04 -0.570 3.24E-07
1110 ILMN .2076463 121260 SLC15A4 0.314 3.78E-04 -0.228 7.90E-03
1111 ILMN .2080611 23590 PDSS1 0.275 2.06E-03 -0.675 2.20E-09
1112 ILMN .2082893 440157 LOC440157 0.263 4.70E-03 -0.362 1.25E-04
1113 ILMN .2083559 9907 KIAA0415 0.490 2.45E-06 -0.303 1.25E-03
1114 ILMN .2084353 4074 M6PR 0.429 1.93E-06 -0.382 7.22E-06
1115 ILMN .2085012 28959 TMEM176B 0.299 3.31E-04 -0.222 5.82E-03
1116 ILMN .2085862 51296 SLC15A3 2.307 4.97E-23 -0.399 1.32E-05
1117 ILMN .2086612 8418 CMAH 0.590 5.16E-07 -0.517 3.27E-06
1118 ILMN .2088847 55593 OTUD5 0.240 2.02E-03 -0.312 2.02E-04
1119 ILMN .2089073 10079 ATP9A 2.432 6.74E-22 -0.660 2.48E-08
1120 ILMN .2091347 3417 IDH1 0.255 7.50E-03 -0.265 5.95E-03
1121 ILMN .2092333 353345 GPR141 0.915 2.00E-12 -0.697 1.17E-09
1122 ILMN .2092441 29967 LRP12 0.971 6.00E-12 -0.352 2.01E-04
1123 ILMN .2092850 10855 HPSE 1.419 2.41E-17 -0.641 3.99E-09
1124 ILMN .2093027 4430 MYOIB 0.819 1.74E-09 -0.263 8.84E-03
1125 ILMN .2094360 7026 NR2F2 0.383 5.25E-04 -0.286 5.23E-03
1126 ILMN .2094856 202151 RANBP3L 0.920 8.59E-12 -0.990 4.50E-13
1127 ILMN .2094942 55016 Mar-01 1.281 2.30E-14 -1.095 1.01E-12
1128 ILMN .2095759 79627 OGFRL1 2.298 5.06E-22 -0.466 2.61E-06
1129 ILMN .2096116 7184 HSP90B 1 0.230 1.45E-03 -0.418 1.14E-06
1130 ILMN .2096372 216 ALDH1A1 0.789 1.53E-10 -1.014 9.46E-14
1131 ILMN .2096784 7022 TFAP2C 0.746 1.03E-09 -0.246 5.41E-03
1132 ILMN .2098126 6352 CCL5 2.856 3.00E-25 -0.353 8.69E-05
1133 ILMN .2100209 9560 CCL4L1 7.281 4.90E-30 -0.551 1.50E-04
1134 ILMN .2102330 1296 COL8A2 0.830 1.16E-11 -1.376 6.86E-17
1135 ILMN .2103107 27299 ADAMDEC1 5.023 1.24E-30 -2.687 3.87E-25
1136 ILMN .2103362 201176 ARHGAP27 0.572 3.32E-09 -0.369 1.21E-05
1137 ILMN .2104830 53 ACP2 1.999 5.21E-19 -0.758 2.92E-09
1138 ILMN .2105573 414062 CCL3L3 6.974 2.65E-33 -0.280 3.09E-03
1139 ILMN .2106449 79666 PLEKHF2 0.631 2.80E-07 -0.349 3.15E-04
1140 ILMN .2106725 654816 NCF1B 1.948 6.75E-20 -1.004 6.60E-13
1141 ILMN .2109197 23136 EPB41L3 3.003 1.08E-24 -1.115 5.45E-15
1142 ILMN .2109343 54557 SGTB 1.595 1.03E-18 -0.337 1.18E-04
1143 ILMN .2109708 1890 ECGF1 1.992 4.88E-21 -0.298 6.36E-04
1144 ILMN .2112988 654817 NCF1C 4.516 1.26E-28 -0.878 1.74E-10
1145 ILMN .2113333 284194 LGALS9B 0.971 1.70E-12 -0.400 2.36E-05
1146 ILMN .2114568 115362 GBP5 3.686 7.58E-27 -0.859 8.46E-11 1147 ILMN .2115005 221472 FGD2 2.558 3.16E-24 -0.511 1.22E-07
1148 ILMN .2115752 4210 MEFV 1.291 3.47E-16 -1.168 1.30E-15
1149 ILMN .2116714 27173 SLC39A1 0.900 1.65E-12 -0.490 4.79E-07
1150 ILMN .2117623 10154 PLXNC1 0.807 1.75E-10 -0.311 4.33E-04
1151 ILMN .2118864 5861 RAB1A 0.445 2.71E-06 -0.247 1.68E-03
1152 ILMN .2119123 2925 GRPR 0.746 8.43E-09 -0.767 1.15E-10
1153 ILMN .2119297 23034 SAMD4A 2.030 3.40E-17 -0.443 2.08E-06
1154 ILMN .2120273 8905 AP1S2 0.941 1.32E-13 -0.302 1.35E-04
1155 ILMN .2123743 2207 FCER1G 1.174 9.17E-16 -0.781 2.34E-11
1156 ILMN .2124471 206358 SLC36A1 0.689 1.43E-09 -0.352 1.41E-04
1157 ILMN .2126832 10802 SEC24A 0.519 4.96E-06 -0.348 5.84E-04
1158 ILMN .2127298 9002 F2RL3 0.577 3.15E-08 -0.644 2.36E-09
1159 ILMN .2129161 2615 LRRC32 0.717 2.50E-07 -0.389 1.04E-03
1160 ILMN .2129202 3448 IFNA14 2.607 3.97E-22 -0.510 4.74E-06
1161 ILMN .2129505 220002 CYBASC3 1.737 1.41E-20 -0.663 3.60E-10
1162 ILMN .2131447 116135 LRRC3B 1.036 1.26E-12 -0.233 8.47E-03
1163 ILMN .2132599 118932 ANKRD22 0.970 8.86E-13 -0.746 3.62E-10
1164 ILMN .2133675 6448 SGSH 2.393 3.51E-23 -0.862 3.71E-12
1165 ILMN .2134974 23682 RAB38 0.552 1.66E-08 -0.533 3.03E-08
1166 ILMN .2138589 10461 MERTK 2.663 1.26E-23 -1.085 1.00E-13
1167 ILMN .2144426 8337 HIST2H2AA3 2.526 1.18E-20 -0.397 3.35E-04
1168 ILMN .2148668 1102 RCBTB2 0.856 8.04E-12 -0.566 4.15E-08
1169 ILMN .2148785 2633 GBP1 5.916 2.78E-33 -1.466 3.52E-17
1170 ILMN .2149624 282618 IL29 2.147 4.12E-20 -0.427 4.54E-05
1171 ILMN .2150654 65249 ZSWIM4 2.676 1.43E-23 -0.385 2.75E-05
1172 ILMN .2152257 6752 SSTR2 0.380 3.05E-03 -0.759 1.36E-07
1173 ILMN .2155480 339122 RAB43 1.271 5.77E-14 -0.417 7.46E-06
1174 ILMN .2157441 3122 HLA-DRA 1.931 3.31E-19 -1.346 3.55E-15
1175 ILMN .2161746 9322 TRIP10 0.610 2.83E-08 -0.447 6.28E-06
1176 ILMN .2163315 388955 LOC388955 0.235 8.44E-03 -0.254 5.06E-03
1177 ILMN .2164242 140739 UBE2F 1.000 1.87E-14 -0.943 6.93E-14
1178 ILMN .2165753 649853 HLA-A29.1 2.044 1.42E-20 -0.344 2.74E-04
1179 ILMN .2166524 151195 CCNYL1 0.852 2.83E-10 -0.272 3.79E-03
1180 ILMN .2170949 29887 SNX10 0.768 7.72E-09 -0.620 1.46E-07
1181 ILMN .2172497 9890 LPPR4 2.022 9.53E-20 -0.353 3.34E-04
1182 ILMN .2172890 6570 SLC18A1 0.963 2.15E-10 -0.694 1.50E-07
1183 ILMN .2174296 27000 DNAJC2 0.461 3.32E-05 -0.357 3.59E-04
1184 ILMN .2174574 10151 HNRNPA3P1 0.820 8.59E-10 -0.812 9.98E-10
1185 ILMN .2175912 3689 ITGB2 0.585 1.71E-08 -0.353 8.64E-05
1186 ILMN .2176063 2209 FCGR1A 1.360 2.70E-16 -0.416 1.82E-05
1187 ILMN .2176225 3467 IFNW1 0.531 2.42E-07 -0.261 2.77E-03
1188 ILMN .2183216 51567 TTRAP 0.270 1.20E-02 -0.400 9.50E-05
1189 ILMN .2183331 10179 RBM7 0.410 2.11E-05 -0.327 3.70E-04
1190 ILMN .2186061 5209 PFKFB3 1.035 1.91E-14 -0.469 4.73E-07 1191 ILMN_ ,2186482 51014 TMED7 0.450 1.84E-06 -0.274 9.42E-04
1192 ILMN_ ,2186745 3444 IFNA7 1.660 3.31E-15 -0.431 2.27E-04
1193 ILMN_ .2188333 969 CD69 0.602 6.34E-07 -0.465 2.38E-06
1194 ILMN_ ,2189027 9388 LIPG 2.180 1.21E-18 -1.936 8.61E-21
1195 ILMN_ ,2191313 387680 FAM21A 0.522 6.83E-07 -0.410 1.70E-05
1196 ILMN_ ,2192072 4316 MMP7 0.538 5.54E-06 -0.633 4.42E-08
1197 ILMN_ ,2193591 81622 UNC93B1 1.100 4.09E-15 -0.545 4.43E-08
1198 ILMN_ ,2193817 339390 CLEC4G 0.243 1.20E-02 -0.411 2.11E-05
1199 ILMN_ ,2195703 133522 PPARGC1B 0.344 1.40E-04 -0.573 4.56E-08
1200 ILMN_ ,2198413 26579 MYEOV 0.992 1.79E-11 -0.792 1.67E-09
1201 ILMN_ ,2198515 57561 ARRDC3 1.111 3.51E-13 -0.308 9.81E-04
1202 ILMN_ ,2198812 2230 FDX I 0.562 8.17E-07 -0.301 6.37E-04
1203 ILMN_ ,2199768 139065 SLITRK4 0.363 2.42E-04 -0.560 3.85E-07
1204 ILMN_ ,2201966 9683 N4BP1 1.060 1.57E-11 -0.451 2.08E-05
1205 ILMN_ ,2203271 2359 FPR3 0.631 6.58E-08 -0.582 3.71E-07
1206 ILMN_ ,2206344 8509 NDST2 0.756 5.24E-10 -0.268 2.96E-03
1207 ILMN_ ,2206812 54619 CCNJ 0.906 1.83E-10 -0.335 1.20E-03
1208 ILMN_ ,2208455 80821 DDHD1 0.397 6.85E-05 -0.285 2.65E-03
1209 ILMN_ ,2210519 1404 HAPLN1 0.257 2.29E-03 -0.234 5.53E-03
1210 ILMN_ ,2214678 4084 MXD1 2.034 6.28E-21 -0.485 3.23E-07
1211 ILMN_ ,2216157 2768 GNA12 0.814 2.15E-12 -0.438 9.95E-07
1212 ILMN_ ,2216838 222161 DKFZP586I1420 0.269 5.14E-03 -0.725 7.84E-09
1213 ILMN_ ,2216918 23729 SHPK 0.214 6.88E-03 -0.749 1.05E-10
1214 ILMN_ ,2218856 6349 CCL3L1 6.439 9.93E-31 -0.609 1.99E-06
1215 ILMN_ ,2222688 7114 TMSB4X 0.865 8.53E-11 -0.829 5.53E-11
1216 ILMN_ ,2223130 8467 SMARCA5 0.584 2.90E-08 -0.337 7.80E-05
1217 ILMN_ ,2226917 9766 KIAA0247 1.871 2.98E-21 -0.593 6.24E-09
1218 ILMN_ ,2228732 901 CCNG2 0.288 1.55E-03 -0.254 4.02E-03
1219 ILMN_ ,2228873 83930 STARD3NL 0.203 5.79E-03 -0.226 2.96E-03
1220 ILMN_ ,2229261 400709 SIGLEC16 1.170 1.43E-13 -0.436 9.84E-06
1221 ILMN_ ,2230016 25994 HIGD1A 0.240 1.22E-02 -0.249 7.55E-03
1222 ILMN_ ,2232121 8477 GPR65 1.464 3.58E-17 -0.732 6.80E-10
1223 ILMN_ ,2232712 4651 MYO10 1.477 5.52E-19 -1.156 3.71E-16
1224 ILMN_ ,2233783 952 CD38 2.486 1.01E-23 -0.548 3.27E-08
1225 ILMN_ ,2235851 93082 LINCR 2.804 8.82E-23 -1.210 1.80E-13
1226 ILMN_ ,2239772 653401 FAM108A3 0.269 1.07E-02 -0.673 1.70E-07
1227 ILMN_ ,2241953 29992 PILRA 1.314 1.47E-13 -0.455 3.60E-06
1228 ILMN_ ,2242937 411 ARSB 0.688 1.93E-10 -0.440 1.43E-06
1229 ILMN_ ,2243308 91 ACVR1B 0.620 5.03E-08 -0.275 2.83E-03
1230 ILMN_ ,2243687 3920 LAMP2 0.451 6.29E-07 -0.257 1.41E-03
1231 ILMN_ ,2245305 26090 ABHD12 0.532 2.96E-07 -0.433 1.05E-05
1232 ILMN_ ,2253732 7903 ST8SIA4 0.575 3.74E-07 -0.614 1.45E-07
1233 ILMN_ ,2259818 4241 MFI2 0.724 2.91E-07 -0.327 2.08E-03 1234 ILMN .2261379 23380 SRGAP2 0.648 7.87E-09 -0.539 2.50E-07
1235 ILMN .2261600 2210 FCGR1B 1.431 1.63E-17 -0.654 2.22E-09
1236 ILMN .2262044 84875 PARP10 2.145 2.46E-20 -0.465 9.91E-06
1237 ILMN .2267787 3257 HPS1 0.309 9.71E-04 -0.255 5.94E-03
1238 ILMN .2275098 113878 DTX2 0.859 5.28E-11 -0.524 6.81E-07
1239 ILMN .2278265 196743 PAOX 1.343 8.59E-14 -1.122 3.77E-13
1240 ILMN .2289593 486 FXYD2 0.310 1.51E-03 -0.302 1.67E-03
1241 ILMN .2289849 2212 FCGR2A 0.407 6.21E-06 -1.099 1.04E-14
1242 ILMN .2290068 10451 VAV3 0.648 1.31E-08 -0.659 2.57E-09
1243 ILMN .2300664 8911 CACNA1I 1.158 4.32E-13 -0.956 3.63E-12
1244 ILMN .2302654 7804 LRP8 0.346 7.96E-04 -0.382 2.73E-04
1245 ILMN .2307903 7412 VCAM1 4.788 9.97E-31 -0.912 4.97E-12
1246 ILMN .2312340 10288 LILRB2 2.640 3.18E-21 -0.751 2.48E-10
1247 ILMN .2313074 9191 DEDD 0.304 9.99E-05 -0.361 1.50E-05
1248 ILMN .2315780 10579 TACC2 0.648 2.19E-09 -0.404 1.08E-05
1249 ILMN .2316386 151306 GPBAR1 0.283 1.39E-03 -0.294 5.52E-04
1250 ILMN .2316844 3516 RBPJ 0.244 6.98E-03 -0.481 3.76E-06
1251 ILMN .2316878 5800 PTPRO 0.386 2.06E-05 -0.445 3.78E-06
1252 ILMN .2318011 5684 PSMA3 0.605 6.65E-09 -0.311 2.92E-04
1253 ILMN .2319000 4145 MATK 0.225 1.05E-02 -0.589 1.18E-07
1254 ILMN .2323491 23636 NUP62 0.458 1.33E-05 -0.578 8.27E-08
1255 ILMN .2325337 23780 APOL2 1.022 5.19E-12 -0.451 1.70E-05
1256 ILMN .2326509 834 CASP1 1.766 5.32E-20 -0.371 3.59E-05
1257 ILMN .2329429 474344 GIMAP6 1.016 1.79E-12 -1.285 4.50E-15
1258 ILMN .2329885 9859 CEP170 0.518 1.51E-07 -0.518 1.61E-07
1259 ILMN .2330845 4905 NSF 0.240 2.30E-03 -0.291 5.00E-04
1260 ILMN .2333774 117289 TAGAP 1.296 8.45E-17 -0.637 1.93E-09
1261 ILMN .2336335 220972 Mar-08 0.267 6.06E-03 -0.256 7.02E-03
1262 ILMN .2336781 6648 SOD2 4.061 4.50E-28 -0.416 2.51E-05
1263 ILMN .2336902 53840 TRIM34 1.126 4.68E-14 -0.233 4.77E-03
1264 ILMN .2339294 10990 LILRB5 1.660 1.06E-16 -0.889 2.92E-10
1265 ILMN .2339748 11342 RNF13 0.625 7.88E-09 -0.271 1.23E-03
1266 ILMN .2340259 5142 PDE4B 2.796 9.94E-26 -0.591 1.73E-09
1267 ILMN .2341254 90627 STARD13 1.125 3.34E-15 -0.848 2.70E-12
1268 ILMN .2342695 5154 PDGFA 1.757 1.82E-14 -0.467 3.08E-04
1269 ILMN .2345898 6503 SLA 0.554 2.90E-07 -0.878 3.71E-11
1270 ILMN .2347145 1634 DCN 1.684 4.04E-18 -1.651 2.01E-18
1271 ILMN .2347592 4828 NMB 0.842 9.97E-11 -0.717 2.03E-09
1272 ILMN .2348268 25900 IFFOl 0.251 4.35E-03 -0.355 1.89E-04
1273 ILMN .2351298 7456 WIPF1 0.582 1.43E-08 -0.501 3.45E-07
1274 ILMN .2352380 7226 TRPM2 1.118 6.49E-13 -1.374 2.22E-15
1275 ILMN .2353633 30817 EMR2 2.198 9.71E-21 -0.924 2.15E-11
1276 ILMN .2354140 51126 NAT5 0.532 2.66E-08 -0.773 1.22E-11
1277 ILMN .2354617 9149 DYRK1B 0.294 5.42E-03 -0.348 6.94E-04 1278 ILMN_ .2355831 2274 FHL2 0.395 1.23E-05 -0.778 2.13E-11
1279 ILMN_ .2355953 11006 LILRB4 0.847 3.86E-13 -0.316 6.68E-05
1280 ILMN_ .2356654 3964 LGALS8 1.328 2.36E-15 -0.298 1.60E-03
1281 ILMN_ .2357134 8877 SPHK1 2.343 1.72E-21 -0.457 1.26E-05
1282 ILMN_ .2360784 6238 RRBP1 1.130 2.12E-15 -0.350 3.15E-05
1283 ILMN_ .2362581 22862 FNDC3A 0.961 5.59E-14 -0.336 6.40E-05
1284 ILMN_ .2363426 4149 MAX 0.778 2.36E-09 -0.317 1.69E-03
1285 ILMN_ .2364022 9123 SLC16A3 0.892 4.51E-13 -0.417 3.46E-06
1286 ILMN_ .2368292 79042 TSEN34 0.771 1.65E-11 -0.212 7.20E-03
TMEM189-
1287 ILMN_ .2368713 387522 0.320 4.22E-05 -0.411 1.91E-06
UBE2V1
1288 ILMN_ .2372413 637 BID 0.677 2.57E-09 -0.314 2.14E-04
1289 ILMN_ .2373831 10384 BTN3A3 1.387 9.28E-17 -0.278 9.80E-04
1290 ILMN_ .2374036 1514 CTSL1 2.343 7.90E-24 -0.896 5.21E-13
1291 ILMN_ .2374340 5329 PLAUR 2.662 1.06E-24 -0.903 1.63E-12
1292 ILMN_ 2374449 6696 SPP1 4.913 8.30E-28 -4.073 4.34E-26
1293 ILMN_ .2376289 28988 DBNL 0.554 4.13E-08 -0.391 1.91E-05
1294 ILMN_ .2376553 9963 SLC23A1 0.403 6.49E-05 -0.302 9.98E-04
1295 ILMN_ .2379130 3654 IRAKI 0.389 2.81E-05 -0.474 1.50E-06
1296 ILMN_ .2379788 3091 HIF1A 0.968 6.01E-12 -0.425 1.15E-05
1297 ILMN_ .2380771 10327 AKR1A1 0.919 8.59E-13 -0.259 1.52E-03
1298 ILMN_ .2383774 7187 TRAF3 0.785 1.41E-11 -0.514 4.48E-08
1299 ILMN_ .2387860 1588 CYP19A1 3.690 1.74E-26 -1.695 3.96E-19
1300 ILMN_ .2389445 55160 ARHGEF10L 0.831 1.59E-08 -0.535 3.41E-06
1301 ILMN_ .2389501 3290 HSD11B1 1.433 1.79E-15 -1.217 6.39E-14
1302 ILMN_ .2390227 23061 TBC1D9B 0.838 1.42E-12 -0.418 2.39E-06
1303 ILMN_ .2390299 5696 PSMB8 0.855 1.07E-12 -0.303 1.91E-04
1304 ILMN_ .2390310 84981 C17orf91 1.585 6.16E-17 -0.434 3.92E-06
1305 ILMN_ .2390853 1512 CTSH 1.862 1.17E-20 -0.728 1.80E-10
1306 ILMN_ .2391976 57210 SLC45A4 0.533 3.35E-06 -0.573 4.19E-07
1307 ILMN_ .2392274 3732 CD82 0.893 3.64E-12 -0.356 9.68E-05
1308 ILMN_ .2392635 23 ABCF1 0.334 9.27E-05 -0.302 2.98E-04
1309 ILMN_ .2393046 387921 NHLRC3 1.028 2.18E-13 -0.519 4.88E-07
1310 ILMN_ .2393296 2710 GK 1.022 1.19E-13 -0.727 3.72E-10
1311 ILMN_ .2395214 91010 FMNL3 1.119 1.46E-13 -0.392 4.34E-05
1312 ILMN_ .2395711 409 ARRB2 0.771 4.36E-10 -0.298 7.67E-04
1313 ILMN_ .2395981 149628 PYHIN1 0.721 2.15E-07 -0.242 5.81E-03
1314 ILMN_ .2396020 1848 DUSP6 2.924 2.21E-24 -0.436 8.74E-06
1315 ILMN_ 2396444 929 CD14 4.167 4.89E-29 -1.969 1.72E-20
1316 ILMN_ .2399919 51085 MLXIPL 2.426 1.70E-21 -0.836 2.67E-10
1317 ILMN_ .2400030 5771 PTPN2 0.405 1.14E-05 -0.394 9.49E-06
1318 ILMN_ .2402416 10049 DNAJB6 0.871 2.82E-10 -0.765 4.12E-09
1319 ILMN_ .2402600 169792 GLIS3 0.937 5.31E-11 -0.557 2.64E-07
1320 ILMN_ .2402805 26133 TRPC4AP 0.842 2.91E-12 -0.366 2.69E-05 1321 ILMN_ ,2404385 29803 REPIN1 0.211 6.00E-03 -0.257 1.48E-03
1322 ILMN_ ,2404688 26471 NUPR1 3.006 1.47E-26 -0.248 1.76E-03
1323 ILMN_ .2405305 406 ARNTL 0.321 3.53E-04 -0.324 3.86E-04
1324 ILMN_ ,2405642 79947 DHDDS 0.466 6.01E-07 -0.242 2.34E-03
1325 ILMN_ .2406035 3909 LAMA3 0.706 1.05E-09 -0.262 2.13E-03
1326 ILMN_ ,2408450 79876 UBE1DC1 0.329 1.21E-04 -0.263 1.34E-03
1327 ILMN_ ,2412024 23210 JMJD6 0.604 2.61E-07 -0.388 1.77E-04
1328 ILMN_ ,2412192 3075 CFH 1.508 2.26E-17 -1.115 4.38E-14
1329 ILMN_ ,2412214 3965 LGALS9 1.614 1.60E-18 -0.576 5.33E-08
1330 ILMN_ 2413644 116211 TM4SF19 0.529 1.87E-06 -0.225 7.01E-03
1331 ILMN_ ,2413808 963 CD53 1.752 4.25E-19 -0.495 1.22E-06
1332 ILMN_ ,2414325 25816 TNFAIP8 1.185 1.66E-13 -0.281 4.13E-03
1333 ILMN_ ,3178302 64778 FNDC3B 1.461 6.14E-19 -0.426 1.32E-06
1334 ILMN_ ,3178529 728917 FAM108A2 0.198 1.09E-02 -0.717 2.27E-10
1335 ILMN_ ,3182275 57700 FAM160B1 0.409 1.71E-04 -0.277 1.30E-03
1336 ILMN_ ,3184334 100130769 LOCI 00130769 0.268 1.74E-03 -0.215 7.95E-03
1337 ILMN_ ,3185784 100125556 LOC100125556 0.290 1.13E-03 -0.355 1.50E-04
1338 ILMN_ ,3187300 100129969 LOCI 00129969 1.018 1.08E-12 -0.238 6.70E-03
1339 ILMN_ ,3190833 9034 CCRL2 2.338 1.44E-21 -0.267 4.01E-03
1340 ILMN_ ,3192493 100128295 LOCI 00128295 0.260 1.46E-03 -0.319 2.03E-04
1341 ILMN_ ,3199438 440366 LOC440366 0.404 5.37E-04 -0.326 1.80E-03
1342 ILMN_ ,3199743 100131706 LOC100131706 0.245 8.86E-03 -0.259 6.67E-03
1343 ILMN_ ,3200362 727908 LOC727908 0.275 7.83E-03 -0.251 5.55E-03
1344 ILMN_ ,3200652 100131308 LOC100131308 0.459 8.11E-05 -0.318 1.45E-03
1345 ILMN_ ,3201643 100133019 LOC100133019 0.404 1.30E-03 -0.356 1.83E-03
1346 ILMN_ ,3205353 100131294 LOC100131294 1.159 l.OlE-11 -0.330 9.32E-04
1347 ILMN_ ,3213640 100132444 LOCI 00132444 0.336 1.27E-03 -0.457 2.93E-05
1348 ILMN_ ,3218538 345645 LOC345645 0.468 8.26E-05 -0.595 3.01E-06
1349 ILMN_ ,3219806 643384 LOC643384 1.207 1.95E-16 -0.434 1.56E-06
1350 ILMN_ ,3222402 730284 LOC730284 0.281 2.28E-03 -0.240 8.08E-03
1351 ILMN_ ,3223317 728666 LOC728666 0.354 2.90E-04 -0.826 1.83E-10
1352 ILMN_ ,3224290 730052 LOC730052 0.395 1.37E-05 -0.381 2.57E-05
1353 ILMN_ ,3224926 54502 RBM47 2.380 1.03E-22 -0.870 1.32E-11
1354 ILMN_ ,3228688 730415 LOC730415 0.709 2.49E-09 -0.379 8.71E-05
1355 ILMN_ ,3229324 6446 SGK1 5.823 3.84E-33 -0.534 2.73E-07
1356 ILMN_ ,3230435 729086 LOC729086 1.459 1.10E-13 -0.539 1.41E-05
1357 ILMN_ ,3233930 390557 LOC390557 0.589 9.60E-09 -0.654 1.79E-09
1358 ILMN_ ,3234828 161145 TMEM229B 0.878 4.36E-11 -0.499 1.57E-06
1359 ILMN_ ,3235467 56286 DAD1L 0.530 6.10E-06 -0.254 5.83E-03
1360 ILMN_ ,3235732 100133095 LOC100133095 0.261 7.80E-03 -0.395 9.29E-06
1361 ILMN_ ,3235755 728830 LOC728830 1.335 8.59E-15 -0.431 2.21E-05
1362 ILMN_ ,3235832 728835 LOC728835 7.666 8.57E-34 -0.610 7.18E-07
1363 ILMN_ ,3235964 3311 HSPA7 0.871 2.08E-11 -0.598 1.51E-08
1364 ILMN_ ,3236049 692057 SNORD12 0.354 4.15E-04 -0.340 3.54E-04 1365 ILMN_ ,3236220 9170 LPAR2 0.501 1.81E-05 -0.459 3.23E-06
1366 ILMN_ .3236391 100132472 LOCI 00132472 0.242 7.79E-03 -0.418 2.98E-05
1367 ILMN_ .3236463 285296 LOC285296 0.990 2.36E-13 -0.520 1.58E-07
1368 ILMN_ .3236752 100132494 LOCI 00132494 0.326 1.74E-03 -0.396 1.50E-04
1369 ILMN_ .3237376 57476 GRAMD1B 0.936 2.48E-12 -0.410 1.09E-05
1370 ILMN_ .3237627 154761 LOCI 54761 0.472 3.77E-05 -0.360 8.88E-04
1371 ILMN_ .3237966 22992 FBXL11 0.509 1.11E-05 -0.460 4.92E-05
1372 ILMN_ .3238359 652725 LOC652725 0.673 4.14E-07 -0.422 1.55E-04
1373 ILMN_ .3238662 692205 SNORD89 0.679 2.05E-08 -0.268 2.49E-03
1374 ILMN_ .3238893 100133459 LOC100133459 0.393 1.53E-04 -0.432 2.84E-05
1375 ILMN_ .3239460 4947 OAZ2 0.560 9.86E-05 -0.556 9.44E-05
1376 ILMN_ .3239965 3620 IDOl 2.895 2.87E-24 -1.279 9.72E-16
1377 ILMN_ .3240117 64853 AIDA 0.630 2.48E-09 -0.236 3.34E-03
1378 ILMN_ .3240308 100133511 LOC100133511 0.891 1.29E-10 -0.310 8.50E-04
1379 ILMN_ .3240316 7117 TMSL3 0.789 3.10E-10 -0.536 6.35E-07
1380 ILMN_ .3241234 730278 LOC730278 0.853 5.96E-11 -0.383 6.09E-05
1381 ILMN_ .3242011 55233 MOBKL1B 1.286 1.14E-15 -0.516 2.24E-07
1382 ILMN_ .3242048 653365 ASAH2C 0.703 2.45E-10 -0.210 7.88E-03
1383 ILMN_ .3242540 283316 CD163L1 0.214 5.95E-03 -0.419 3.77E-06
1384 ILMN_ .3242900 723790 HIST2H2AA4 2.254 8.06E-20 -0.344 8.43E-04
1385 ILMN_ .3243061 100049587 SIGLEC14 1.989 2.36E-21 -1.024 6.89E-14
1386 ILMN_ .3243714 642073 LOC642073 0.680 3.79E-08 -0.514 2.42E-06
1387 ILMN_ 3244457 254102 EHBP1L1 0.766 1.24E-09 -0.585 1.57E-07
1388 ILMN_ .3244550 642413 LOC642413 0.595 7.78E-07 -0.377 8.14E-05
1389 ILMN_ .3244935 100130308 LOCI 00130308 0.632 4.13E-09 -0.287 7.98E-04
1390 ILMN_ .3245066 9909 DENND4B 0.356 2.21E-04 -0.325 5.07E-04
1391 ILMN_ .3245390 392635 LOC392635 0.784 1.47E-08 -0.419 1.87E-04
1392 ILMN_ .3245507 100133627 LOC100133627 0.312 6.90E-04 -0.321 5.89E-04
1393 ILMN_ .3245569 731528 LOC731528 0.313 3.03E-03 -0.320 1.99E-03
1394 ILMN_ .3246054 732415 LOC732415 0.605 2.52E-06 -0.364 1.15E-03
1395 ILMN_ .3247261 9693 RAPGEF2 1.349 1.70E-16 -0.470 1.79E-06
1396 ILMN_ .3247506 100132417 FCGR1C 1.276 1.42E-14 -0.495 4.25E-06
1397 ILMN_ .3247848 147650 NCRNA00085 0.650 3.43E-08 -0.371 1.60E-04
1398 ILMN_ .3247998 26228 ST API 3.391 1.08E-26 -0.849 1.81E-11
1399 ILMN_ .3248910 114614 MIR155HG 1.154 3.79E-14 -0.392 4.89E-05
1400 ILMN_ .3249667 100133678 LOC100133678 0.873 3.02E-13 -0.639 5.58E-10
1401 ILMN_ .3251658 79168 LILRA6 2.581 3.72E-22 -1.321 3.21E-15
1402 ILMN_ .3253304 730010 BRI3P1 1.225 4.12E-15 -0.477 2.07E-06
1403 ILMN_ .3253787 100128274 LOCI 00128274 1.831 6.63E-16 -0.630 1.61E-07
1404 ILMN_ .3256478 100129034 LOCI 00129034 0.684 3.29E-08 -0.386 2.01E-04
1405 ILMN_ .3258346 100130009 LOCI 00130009 0.281 4.39E-03 -0.348 5.89E-04
1406 ILMN_ .3258424 100129118 LOC100129118 0.319 8.96E-05 -0.370 2.01E-05
1407 ILMN_ .3259146 100129681 LOCI 00129681 1.147 5.59E-14 -0.456 6.83E-06
1408 ILMN_ .3261747 100128729 LOCI 00128729 0.308 2.10E-03 -0.301 8.39E-04 1409 ILMN_ .3271555 100130458 LOC100130458 0.439 4.91E-05 -0.302 1.47E-03
1410 ILMN_ .3273209 379034 FLJ 10489 0.390 5.18E-04 -0.417 6.90E-05
1411 ILMN_ .3278642 641922 LOC641922 0.922 6.64E-10 -0.452 7.63E-05
1412 ILMN_ .3278735 389465 LOC389465 0.797 1.13E-09 -0.551 1.14E-06
1413 ILMN_ .3282506 728098 LOC728098 0.311 1.02E-03 -0.236 7.90E-03
1414 ILMN_ .3294741 644496 LOC644496 1.414 3.82E-12 -0.973 1.04E-10
1415 ILMN_ .3295075 100131531 LOC100131531 0.340 7.24E-05 -0.473 4.07E-07
1416 ILMN_ .3295494 389386 LOC389386 2.115 1.04E-20 -0.414 2.81E-05
1417 ILMN_ .3304012 729806 LOC729806 0.739 3.42E-10 -0.254 2.16E-03
1418 ILMN_ .3305378 729839 LOC729839 0.848 8.61E-11 -0.363 1.19E-04
1419 ILMN_ .3306854 729770 LOC729770 0.274 2.47E-03 -0.246 5.99E-03
1420 ILMN_ .3307700 60559 SPCS3 0.639 1.06E-09 -0.302 2.75E-04
1421 ILMN_ .3307772 11252 PACSIN2 0.548 1.36E-06 -0.380 3.76E-05
1422 ILMN_ .3307868 1116 CHI3L1 0.977 6.46E-10 -0.392 6.56E-04
1423 ILMN_ .3307916 168667 BMPER 0.803 1.07E-08 -0.635 6.05E-07
1424 ILMN_ .3307935 57194 ATP10A 0.393 7.90E-05 -0.485 3.22E-06
1425 ILMN_ .3308843 100302277 MIR548I2 0.230 4.46E-03 -0.225 6.11E-03
1426 ILMN_ .3309664 100126297 MIR300 0.327 1.02E-03 -0.254 8.20E-03
1427 ILMN_ .1651237 81620 CDT1 -1.197 4.38E-13 0.281 6.06E-03
1428 ILMN_ .1651347 9792 SERTAD2 -0.307 1.82E-04 0.990 8.95E-14
1429 ILMN_ .1651364 84105 PCBD2 -0.520 5.61E-06 0.263 8.16E-03
1430 ILMN_ .1651433 1633 DCK -0.417 1.06E-05 0.281 1.37E-03
1431 ILMN_ .1651705 847 CAT -2.235 6.05E-22 0.485 1.56E-06
1432 ILMN_ .1651886 55280 CWF19L1 -0.228 4.21E-03 0.423 4.88E-06
1433 ILMN_ .1651987 154467 C6orfl29 -0.670 1.18E-08 0.374 1.51E-04
1434 ILMN_ .1652123 3150 HMGN1 -0.480 8.56E-07 0.446 2.25E-06
1435 ILMN_ .1652163 1856 DVL2 -0.239 6.53E-03 0.249 4.71E-03
1436 ILMN_ .1652333 79672 FN3KRP -0.449 1.74E-06 0.620 6.37E-09
1437 ILMN_ .1652602 256329 Cl lorf35 -0.704 1.30E-07 0.367 9.39E-04
1438 ILMN_ .1652638 116064 LRRC58 -0.578 4.65E-07 0.277 4.03E-03
1439 ILMN_ .1652735 5994 RFXAP -0.514 2.58E-07 0.265 1.92E-03
1440 ILMN_ .1652753 80227 PAAF1 -0.429 2.41E-06 0.377 1.44E-05
1441 ILMN_ .1652754 126299 ZNF428 -0.631 8.56E-08 0.557 7.93E-07
1442 ILMN_ .1652907 988 CDC5L -0.231 5.24E-03 0.510 3.96E-07
1443 ILMN_ .1652940 113691 MGC 16703 -0.211 9.77E-03 0.324 1.76E-04
1444 ILMN_ .1653115 1891 ECH1 -1.057 8.21E-13 0.445 1.31E-05
1445 ILMN_ .1653133 152503 SH3D19 -0.295 2.05E-03 0.393 7.65E-05
1446 ILMN_ .1653372 148229 ATP8B3 -0.759 1.02E-09 0.568 1.90E-07
1447 ILMN_ .1653429 23443 SLC35A3 -0.223 8.60E-03 0.448 2.98E-06
1448 ILMN_ .1653553 283643 C14orf80 -0.944 1.62E-12 0.415 1.56E-05
1449 ILMN_ .1653618 26009 ZZZ3 -0.509 5.06E-08 0.684 2.01E-10
1450 ILMN_ .1653648 81491 GPR63 -0.742 1.99E-09 0.668 7.70E-09
1451 ILMN_ .1653709 26520 TIMM9 -0.250 6.12E-03 0.336 1.95E-04
1452 ILMN_ .1653718 130617 ZFAND2B -0.459 6.44E-06 0.724 2.22E-09 1453 ILMN_ .1653794 387066 C6orfl60 -0.226 7.89E-03 0.267 2.38E-03
1454 ILMN_ .1653861 22955 SCMH1 -0.704 1.61E-10 0.393 1.06E-05
1455 ILMN_ .1654217 4355 MPP2 -0.470 1.56E-05 0.362 4.01E-04
1456 ILMN_ .1654324 26508 HEYL -0.797 1.47E-10 0.700 3.23E-10
1457 ILMN_ .1654468 56 ACRV1 -0.448 2.71E-04 0.482 8.21E-05
1458 ILMN_ .1654563 1947 EFNB1 -0.445 1.98E-05 0.522 1.65E-06
1459 ILMN_ .1654571 23149 FCHOl -0.460 2.34E-04 0.308 2.90E-03
1460 ILMN_ .1655311 145853 LOC145853 -0.935 6.13E-13 0.457 1.93E-06
1461 ILMN_ .1655382 64858 DCLRE1B -0.379 8.16E-05 0.456 5.29E-06
1462 ILMN_ .1655498 146378 FLJ25404 -1.188 1.22E-12 0.519 2.05E-06
1463 ILMN_ .1655545 84217 ZMYND12 -0.266 1.11E-03 0.922 7.86E-13
1464 ILMN_ .1655642 55215 FANCI -0.941 5.53E-12 0.957 4.75E-12
1465 ILMN_ .1655663 10609 SC65 -0.402 7.67E-05 0.269 4.59E-03
1466 ILMN_ .1655733 5982 RFC2 -0.506 6.94E-07 0.425 1.11E-05
1467 ILMN_ .1655734 80135 RPF1 -0.244 2.93E-03 0.248 2.12E-03
1468 ILMN_ .1655748 64288 ZNF323 -1.166 7.65E-16 0.243 1.78E-03
1469 ILMN_ .1655842 442597 LOC442597 -0.993 6.57E-13 1.302 1.13E-15
1470 ILMN_ .1655913 4925 NUCB2 -1.606 1.71E-17 0.686 1.62E-09
1471 ILMN_ .1656111 29116 MYLIP -0.548 8.35E-08 0.613 1.21E-08
1472 ILMN_ .1656145 2805 GOT1 -0.294 5.90E-04 1.342 1.34E-16
1473 ILMN_ .1656300 2675 GFRA2 -0.329 3.49E-04 0.371 1.08E-04
1474 ILMN_ .1656368 8659 ALDH4A1 -0.429 1.22E-05 0.235 5.08E-03
1475 ILMN_ .1656452 80178 C16orf59 -0.982 9.20E-13 0.617 2.55E-08
1476 ILMN_ .1656691 26272 FBX04 -0.642 4.60E-10 0.397 4.08E-06
1477 ILMN_ .1656900 6817 SULT1A1 -0.363 1.26E-04 0.322 4.21E-04
1478 ILMN_ .1656913 4190 MDH1 -0.463 4.14E-07 0.291 3.42E-04
1479 ILMN_ .1656920 1396 CRIPl -1.562 2.72E-18 1.088 2.41E-14
1480 ILMN_ .1657204 10055 SAE1 -0.547 2.65E-08 0.321 1.51E-04
1481 ILMN_ .1657475 2592 GALT -0.344 7.91E-05 0.511 2.57E-07
1482 ILMN_ .1657509 283989 TSEN54 -0.283 2.29E-03 0.285 1.50E-03
1483 ILMN_ .1657515 9252 RPS6KA5 -0.528 7.58E-07 0.421 8.18E-06
1484 ILMN_ .1657547 91057 CCDC34 -1.605 2.80E-18 0.920 2.72E-12
1485 ILMN_ .1657796 3925 STMN1 -1.650 1.52E-19 0.228 3.56E-03
1486 ILMN_ .1657797 9158 FIBP -0.425 1.50E-06 0.413 3.78E-06
1487 ILMN_ .1658027 8438 RAD54L -0.957 1.09E-12 0.542 1.96E-07
1488 ILMN_ .1658040 1381 CRABP1 -0.795 2.08E-10 0.272 2.93E-03
1489 ILMN_ .1658221 5429 POLH -0.296 7.15E-04 0.289 7.19E-04
1490 ILMN_ .1658289 84058 WDR54 -1.557 4.52E-17 0.789 1.93E-10
1491 ILMN_ .1658373 9924 PAN2 -0.876 5.61E-11 0.463 9.28E-06
1492 ILMN_ .1658425 1605 DAG1 -0.348 1.16E-04 0.315 3.61E-04
1493 ILMN_ .1658639 283537 SLC46A3 -0.607 1.08E-07 0.473 7.39E-06
1494 ILMN_ .1658677 196403 DTX3 -0.204 1.05E-02 0.261 1.76E-03
1495 ILMN_ .1658821 90378 SAMD1 -0.510 1.93E-06 0.273 2.78E-03
1496 ILMN_ .1658847 441478 MGC61598 -0.667 1.53E-08 0.562 2.66E-07 1497 ILMN_ .1658883 369 ARAF -0.230 4.49E-03 0.349 6.04E-05
1498 ILMN_ .1658884 23200 ATP11B -0.275 2.45E-03 0.318 5.88E-04
1499 ILMN_ .1659017 119710 Cl lorf74 -0.367 9.86E-06 0.599 3.00E-09
1500 ILMN_ .1659297 8323 FZD6 -0.467 3.22E-06 0.392 3.67E-05
1501 ILMN_ .1659339 26610 ELP4 -0.563 1.94E-07 0.300 1.30E-03
1502 ILMN_ .1659364 5985 RFC5 -1.203 7.18E-17 0.945 4.25E-14
1503 ILMN_ .1660063 56655 POLE4 -0.552 3.56E-08 0.684 5.78E-10
1504 ILMN_ .1660111 7347 UCHL3 -0.544 2.54E-08 0.438 9.90E-07
1505 ILMN_ .1660133 645566 LOC645566 -0.630 6.98E-09 0.260 2.00E-03
1506 ILMN_ .1660222 27085 MTBP -0.462 1.37E-06 0.339 1.53E-04
1507 ILMN_ .1660426 10898 CPSF4 -0.388 1.90E-05 0.500 5.43E-07
1508 ILMN_ .1660729 245973 ATP6V1C2 -0.266 3.12E-03 0.401 1.98E-05
1509 ILMN_ .1660749 79058 ASPSCR1 -0.476 2.55E-07 0.444 1.21E-06
1510 ILMN_ .1660810 55761 TTC17 -0.483 4.01E-06 0.551 2.87E-07
1511 ILMN_ .1661264 6472 SHMT2 -0.208 9.83E-03 0.450 3.02E-06
1512 ILMN_ .1661432 348995 NUP43 -0.654 4.10E-09 0.423 9.73E-06
1513 ILMN_ .1661595 388722 Clorf53 -0.518 3.10E-07 0.653 5.17E-09
1514 ILMN_ .1661622 51256 TBC1D7 -0.240 7.15E-03 0.453 7.41E-06
1515 ILMN_ .1661653 55070 DET1 -0.629 7.02E-09 0.591 1.31E-08
1516 ILMN_ .1661657 7221 TRPC2 -0.731 6.63E-09 0.482 3.61E-06
1517 ILMN_ .1661809 79056 PRRG4 -0.396 9.71E-05 0.356 1.85E-04
1518 ILMN_ .1661917 644039 LOC644039 -0.214 7.34E-03 0.220 6.40E-03
1519 ILMN_ .1661940 23261 CAMTA1 -0.784 7.55E-11 0.651 4.73E-09
1520 ILMN_ .1662130 730316 LOC730316 -0.447 2.99E-06 0.262 1.36E-03
1521 ILMN_ .1662184 375444 C5orf34 -0.569 4.69E-08 0.905 2.95E-12
1522 ILMN_ .1662243 3621 ING1 -0.395 1.64E-05 0.391 2.55E-05
1523 ILMN_ .1662328 26505 CNNM3 -0.603 4.97E-08 0.471 4.52E-06
1524 ILMN_ .1662483 11042 SMA5 -0.453 3.25E-07 0.380 8.59E-06
1525 ILMN_ .1663195 4176 MCM7 -1.135 2.67E-15 0.554 4.10E-08
1526 ILMN_ .1663407 6834 SURF1 -0.389 4.60E-05 0.509 1.14E-06
1527 ILMN_ .1663538 171425 CLYBL -0.681 4.74E-10 0.567 3.15E-08
1528 ILMN_ .1663793 116449 MIST -0.214 5.73E-03 0.281 6.32E-04
1529 ILMN_ .1664014 219736 STOX1 -0.508 8.49E-06 0.741 4.26E-09
1530 ILMN_ 1664644 89849 ATG16L2 -1.168 4.72E-13 0.891 2.27E-10
1531 ILMN_ .1664912 3590 IL11RA -0.759 1.64E-08 0.290 5.83E-03
1532 ILMN_ .1664922 2317 FLNB -0.571 2.48E-07 0.281 2.71E-03
1533 ILMN_ .1664956 29101 SSU72 -0.344 1.16E-04 0.349 1.33E-04
1534 ILMN_ .1665331 275 AMT -0.479 1.39E-05 0.256 7.44E-03
1535 ILMN_ .1665526 6919 TCEA2 -0.774 1.67E-09 0.496 3.30E-06
1536 ILMN_ .1665538 6502 SKP2 -1.275 3.36E-16 0.238 3.85E-03
1537 ILMN_ .1665559 1017 CDK2 -0.711 4.22E-10 0.698 8.89E-10
1538 ILMN_ .1665686 63895 FAM38B -0.384 1.15E-04 0.478 6.52E-06
1539 ILMN_ .1665775 54996 MOSC2 -0.340 5.24E-04 0.467 6.72E-06
1540 ILMN_ .1665859 5873 RAB27A -1.171 8.71E-15 0.327 3.20E-04 1541 ILMN_ .1665943 11184 MAP4K1 -1.895 6.52E-21 0.545 1.42E-08
1542 ILMN_ .1666178 90313 TP53I13 -0.793 3.77E-11 0.652 2.99E-09
1543 ILMN_ .1666214 646012 LOC646012 -0.355 5.19E-04 0.292 3.40E-03
1544 ILMN_ .1666305 1033 CDKN3 -1.412 2.74E-17 0.289 7.73E-04
1545 ILMN_ .1666364 93058 COQ10A -0.765 3.18E-09 1.030 3.19E-12
1546 ILMN_ .1666372 10476 ATP5H -0.490 1.17E-07 0.292 3.45E-04
1547 ILMN_ .1666512 6499 SKIV2L -0.274 7.17E-04 0.223 5.31E-03
1548 ILMN_ .1666615 9581 PREPL -0.670 5.78E-09 0.416 2.04E-05
1549 ILMN_ .1666894 1464 CSPG4 -0.585 2.64E-07 0.386 7.90E-05
1550 ILMN_ .1666924 65018 PINK1 -1.288 2.74E-17 0.655 5.05E-10
1551 ILMN_ .1666933 9070 ASH2L -0.426 1.80E-06 0.512 1.32E-07
1552 ILMN_ .1667016 11124 FAF1 -0.731 4.12E-10 0.435 7.32E-06
1553 ILMN_ .1667260 5595 MAPK3 -0.505 2.29E-06 0.264 5.06E-03
1554 ILMN_ .1667577 9836 LCMT2 -0.388 5.52E-05 0.740 5.55E-10
1555 ILMN_ .1667670 10166 SLC25A15 -1.321 1.38E-17 0.293 2.53E-04
1556 ILMN_ .1667839 55148 UBR7 -0.691 3.57E-10 0.386 1.48E-05
1557 ILMN_ .1667932 652726 LOC652726 -1.233 2.68E-12 0.362 1.79E-03
1558 ILMN_ .1668247 4056 LTC4S -0.970 8.01E-13 0.449 3.91E-06
1559 ILMN_ .1668312 56606 SLC2A9 -1.099 8.66E-15 0.456 1.48E-06
1560 ILMN_ .1668507 23576 DDAH1 -1.105 2.48E-14 0.884 2.65E-12
1561 ILMN_ .1668582 51185 CRBN -0.330 2.18E-04 0.491 1.09E-06
1562 ILMN_ .1668629 401115 LOC401115 -0.437 2.12E-06 0.492 4.10E-07
1563 ILMN_ .1668649 84073 MYCBPAP -0.293 1.47E-03 0.441 5.93E-07
1564 ILMN_ .1668910 27141 CIDEB -1.099 4.80E-14 0.422 9.05E-06
1565 ILMN_ .1668984 201305 SPNS3 -0.851 4.01E-10 0.484 1.17E-05
1566 ILMN_ .1669064 55552 ZNF823 -0.514 1.80E-07 0.569 4.12E-08
1567 ILMN_ .1669094 79894 ZNF672 -0.228 8.49E-03 0.635 1.92E-08
1568 ILMN_ .1669366 8100 IFT88 -0.533 1.03E-07 0.530 1.32E-07
1569 ILMN_ .1669484 11180 WDR6 -0.978 3.56E-13 0.925 1.93E-12
1570 ILMN_ .1669516 7746 ZNF193 -0.254 2.10E-03 0.659 1.77E-09
1571 ILMN_ .1669550 10459 MAD2L2 -0.516 3.36E-08 0.216 4.27E-03
1572 ILMN_ .1669631 2743 GLRB -0.230 4.86E-03 0.828 2.08E-11
1573 ILMN_ .1669788 256281 NUDT14 -0.360 8.03E-06 0.789 3.78E-12
1574 ILMN_ .1669881 27075 TSPAN13 -0.637 1.30E-07 0.623 5.39E-08
1575 ILMN_ .1669888 1475 CSTA -0.378 2.37E-04 0.466 2.06E-05
1576 ILMN_ .1669905 167227 DCP2 -1.429 2.64E-17 0.586 2.50E-08
1577 ILMN_ .1669928 27237 ARHGEF16 -0.763 1.55E-10 0.531 2.58E-07
1578 ILMN_ .1669940 55151 TMEM38B -0.719 8.54E-10 0.693 2.27E-09
DKFZp6860241
1579 ILMN_ .1669972 374383 -0.246 2.85E-03 0.633 4.91E-09
1580 ILMN_1670000 55827 DCAF6 -1.104 2.58E-13 0.344 3.69E-04
1581 ILMN_1670134 3992 FADS1 -0.664 2.27E-09 0.655 3.05E-09
1582 ILMN_1670218 118460 EXOSC6 -0.399 8.85E-06 0.353 5.14E-05
1583 ILMN_1670238 8318 CDC45L -0.996 4.17E-14 0.733 6.80E-11 1584 ILMN_ .1670263 163882 Clorf71 -0.278 2.15E-03 0.569 1.51E-07
1585 ILMN_ .1670353 10635 RAD51AP1 -1.126 2.96E-13 0.565 6.27E-08
1586 ILMN_ .1670398 613 BCR -0.283 4.26E-03 0.269 6.16E-03
1587 ILMN_ .1670769 55166 CENPQ -0.415 1.32E-05 0.417 1.66E-05
1588 ILMN_ .1670841 8904 CPNE1 -0.593 1.56E-09 0.406 2.01E-06
1589 ILMN_ .1671265 3622 ING2 -0.427 7.54E-05 0.375 1.55E-04
1590 ILMN_ .1671292 390705 LOC390705 -0.463 3.24E-05 0.395 9.62E-05
1591 ILMN_ .1671314 8409 UXT -0.445 2.76E-07 0.269 5.61E-04
1592 ILMN_ 1671404 6840 SVIL -1.237 8.74E-16 0.919 1.69E-12
1593 ILMN_ .1671486 9455 HOMER2 -1.189 2.87E-14 0.475 5.01E-06
1594 ILMN_ .1671621 5110 PCMT1 -0.455 1.90E-06 0.546 7.63E-08
1595 ILMN_ .1671800 643911 LOC643911 -1.026 1.88E-10 0.396 2.98E-04
1596 ILMN_ .1672536 2192 FBLN1 -0.440 1.05E-06 0.437 1.72E-06
1597 ILMN_ .1672717 80195 C10orf57 -0.478 1.87E-06 0.415 1.51E-05
1598 ILMN_ .1672908 7291 TWIST1 -0.208 1.28E-02 0.481 7.89E-07
1599 ILMN_ .1673026 54927 CHCHD3 -0.523 1.58E-07 0.240 4.33E-03
1600 ILMN_ .1673275 6399 TRAPPC2 -0.893 7.45E-11 0.492 6.40E-06
1601 ILMN_ .1673478 51306 C5orf5 -0.733 2.77E-10 0.428 6.33E-06
1602 ILMN_ .1673637 201780 SLC10A4 -0.926 8.93E-12 0.337 4.12E-04
1603 ILMN_ .1673673 55872 PBK -1.452 6.18E-17 0.441 7.77E-06
1604 ILMN_ .1673721 9156 EXOl -1.303 9.25E-17 1.218 6.55E-16
1605 ILMN_ .1673820 6596 HLTF -0.806 4.44E-11 0.664 3.47E-09
1606 ILMN_ .1673933 440341 LOC440341 -0.532 9.69E-07 0.558 4.18E-07
1607 ILMN_ .1674032 5825 ABCD3 -0.948 6.70E-13 0.395 1.23E-05
1608 ILMN_ .1674231 8208 CHAF1B -0.818 2.06E-11 0.891 3.73E-12
1609 ILMN_ .1674302 5471 PPAT -0.403 3.30E-05 0.341 2.98E-04
1610 ILMN_ 1674344 84552 PARD6G -0.519 1.53E-06 0.370 1.32E-04
1611 ILMN_ .1674385 10971 YWHAQ -0.342 7.04E-05 0.275 1.06E-03
1612 ILMN_ .1674411 26586 CKAP2 -0.872 6.36E-12 0.345 1.45E-04
1613 ILMN_ .1674661 1153 CIRBP -0.282 1.03E-03 0.339 1.26E-04
1614 ILMN_ .1674859 651576 LOC651576 -0.802 2.22E-09 0.268 4.96E-03
1615 ILMN_ .1675007 79149 ZSCAN5A -0.569 5.90E-08 0.227 7.61E-03
1616 ILMN_ .1675268 4038 LRP4 -0.417 1.49E-04 0.272 6.53E-04
1617 ILMN_ .1675483 51281 ANKMY1 -0.440 8.98E-06 0.575 1.47E-07
1618 ILMN_ .1675706 337 APOA4 -0.273 2.60E-03 0.252 3.44E-03
1619 ILMN_ .1675797 54749 EPDR1 -0.420 2.65E-05 0.369 1.23E-04
1620 ILMN_ .1676159 51765 MST4 -1.010 1.94E-14 0.770 1.04E-11
1621 ILMN_ .1676197 84918 LRP11 -0.576 1.54E-08 1.118 7.09E-15
1622 ILMN_ .1676555 79989 TTC26 -0.352 8.86E-05 0.238 5.42E-03
1623 ILMN_ .1676611 29085 PHPT1 -0.422 3.29E-06 0.284 4.50E-04
1624 ILMN_ .1676631 10309 CCNO -0.349 1.72E-04 0.597 4.35E-08
1625 ILMN_ .1676946 10947 AP3M2 -0.912 3.66E-12 0.873 1.42E-11
1626 ILMN_ .1676986 9284 NPIP -0.382 9.50E-05 0.321 7.57E-04
1627 ILMN_ .1677043 8574 AKR7A2 -1.242 1.85E-16 0.738 6.86E-11 1628 ILMN_ .1677080 56912 Cl lorf60 -0.328 7.23E-04 0.293 1.62E-03
1629 ILMN_ .1677122 130074 FAM168B -1.090 2.43E-14 0.574 3.14E-08
1630 ILMN_ .1677200 26999 CYFIP2 -0.402 9.37E-05 0.543 1.17E-06
1631 ILMN_ .1677239 64770 CCDC14 -1.128 2.17E-13 1.012 3.36E-12
1632 ILMN_ .1677261 11178 LZTS1 -0.545 9.43E-08 0.723 4.06E-10
1633 ILMN_ .1677385 114926 C8orf40 -0.563 3.84E-08 0.816 2.70E-11
1634 ILMN_ .1678037 8479 HIRIP3 -0.940 7.11E-14 0.616 1.66E-09
1635 ILMN_ .1678435 79644 SRD5A3 -0.662 2.24E-09 0.404 1.75E-05
1636 ILMN_ .1678619 26007 DAK -0.329 2.87E-04 0.329 2.10E-04
1637 ILMN_ .1678669 6241 RRM2 -0.765 7.85E-10 1.444 2.16E-16
1638 ILMN_ .1678705 284131 FLJ35220 -0.268 2.35E-03 0.493 1.09E-06
1639 ILMN_ .1678781 115703 SNX26 -2.141 3.50E-18 0.985 9.84E-11
1640 ILMN_ .1679071 345778 MTX3 -0.634 4.89E-08 0.329 7.13E-04
1641 ILMN_ .1679232 57498 KIDINS220 -0.341 4.48E-04 0.460 8.47E-06
1642 ILMN_ .1679438 79682 MLF1IP -1.179 1.14E-15 1.243 3.49E-16
1643 ILMN_ .1679460 8496 PPFIBP1 -0.545 1.51E-05 0.633 7.22E-07
1644 ILMN_ .1679614 27352 SGSM3 -0.429 5.73E-06 0.328 2.16E-04
1645 ILMN_ .1679880 79228 THOC6 -0.563 4.51E-08 0.448 2.88E-06
1646 ILMN_ .1679919 84164 ASCC2 -0.198 1.23E-02 0.305 2.90E-04
1647 ILMN_ .1680453 81618 ITM2C -1.156 1.64E-15 0.373 2.17E-05
1648 ILMN_ .1680614 440248 LOC440248 -0.243 4.08E-03 0.295 7.87E-04
1649 ILMN_ .1680673 221294 NT5DC1 -0.726 2.64E-10 0.620 6.01E-09
1650 ILMN_ .1680727 51022 GLRX2 -0.328 4.55E-04 0.695 6.98E-10
1651 ILMN_ .1680925 9368 SLC9A3R1 -1.166 3.45E-14 0.841 6.08E-11
1652 ILMN_ .1680928 26052 DNM3 -0.357 3.11E-04 0.406 2.88E-05
1653 ILMN_ .1681118 65981 CAPRIN2 -0.296 9.14E-04 1.002 9.73E-14
1654 ILMN_ .1681249 55605 KIF21A -0.360 4.92E-05 0.856 5.35E-12
1655 ILMN_ .1681269 8798 DYRK4 -0.184 8.66E-03 0.608 1.03E-09
1656 ILMN_ .1681340 51668 Clorf41 -0.636 9.73E-09 0.547 1.67E-07
1657 ILMN_ .1681437 51181 DCXR -0.969 2.67E-14 1.308 2.37E-17
1658 ILMN_ .1681737 11013 TMSB15A -1.626 4.66E-19 1.435 8.41E-18
1659 ILMN_ .1681747 132707 LOCI 32707 -0.247 3.69E-03 0.228 6.77E-03
1660 ILMN_ .1681754 8836 GGH -0.896 2.42E-12 0.967 1.71E-13
1661 ILMN_ .1681829 80095 ZNF606 -0.314 2.09E-04 0.539 4.15E-08
1662 ILMN_ .1682095 55758 RCOR3 -0.603 1.20E-08 0.559 6.52E-08
1663 ILMN_ .1682226 24146 CLDN15 -0.550 2.31E-07 0.556 1.97E-07
1664 ILMN_ .1682288 728565 LOC728565 -0.479 5.62E-06 0.404 2.45E-05
1665 ILMN_ .1682368 222229 LRWD1 -0.247 3.50E-03 0.287 1.11E-03
1666 ILMN_ .1682727 221895 JAZF1 -0.372 8.99E-05 0.435 1.35E-05
1667 ILMN_ .1682774 93081 C13orf27 -1.370 1.61E-14 0.809 2.06E-10
1668 ILMN_ .1682864 90864 SPSB3 -0.332 5.31E-04 0.288 2.31E-03
1669 ILMN_ .1682910 51000 SLC35B3 -0.254 4.96E-03 0.477 5.02E-06
1670 ILMN_ .1683059 23408 SIRT5 -0.415 3.49E-05 0.400 7.29E-05
1671 ILMN_ .1683120 7374 UNG -1.182 1.98E-14 0.895 5.62E-12 1672 ILMN_ .1683175 138716 C9orf23 -0.486 9.51E-07 0.494 1.08E-06
1673 ILMN_ .1683204 26205 GMEB2 -0.230 7.65E-03 0.357 1.05E-04
1674 ILMN_ .1683450 113130 CDCA5 -0.861 6.05E-11 0.759 9.44E-10
1675 ILMN_ .1683462 2937 GSS -0.373 1.28E-05 0.325 1.08E-04
1676 ILMN_ .1683533 285331 CCDC66 -0.442 2.78E-05 0.400 1.03E-04
1677 ILMN_ .1683552 400174 LOC400174 -0.298 1.94E-03 0.265 5.61E-03
1678 ILMN_ .1683660 8667 EIF3H -0.211 7.74E-03 0.294 5.86E-04
1679 ILMN_ .1683755 9580 SOX 13 -0.363 6.79E-05 0.625 8.85E-09
1680 ILMN_ .1683859 6541 SLC7A1 -0.430 2.12E-06 0.581 1.69E-08
1681 ILMN_ .1683927 3682 ITGAE -0.743 2.09E-11 0.345 4.28E-05
1682 ILMN_ .1684158 84706 GPT2 -0.818 3.06E-12 1.155 4.70E-16
1683 ILMN_ .1684205 10519 CIB1 -0.280 2.29E-04 0.308 1.23E-04
1684 ILMN_ .1684210 57185 NPAL3 -1.200 7.14E-16 0.595 8.75E-09
1685 ILMN_ .1684217 9212 AURKB -0.965 9.40E-11 0.283 3.49E-03
1686 ILMN_ .1684306 6275 S100A4 -1.973 8.37E-21 0.272 1.77E-03
1687 ILMN_ .1684321 80777 CYB5B -0.217 8.54E-03 0.311 3.80E-04
1688 ILMN_ .1684352 80263 TRIM45 -0.946 8.07E-12 0.430 1.48E-05
1689 ILMN_ .1684357 79686 C14orfl39 -0.634 8.83E-09 0.331 2.86E-04
1690 ILMN_ .1684563 139886 SPIN4 -1.185 1.78E-13 0.781 6.07E-10
1691 ILMN_ .1684628 146198 ZFP90 -0.445 1.96E-06 0.459 1.69E-06
1692 ILMN_ .1684663 54503 ZDHHC13 -0.298 6.28E-04 0.306 5.14E-04
1693 ILMN_ .1684771 10857 PGRMC1 -0.619 1.15E-09 0.240 2.20E-03
1694 ILMN_ .1684873 414 ARSD -0.334 6.78E-05 0.838 4.51E-12
1695 ILMN_ .1685009 3684 ITGAM -0.562 1.26E-08 1.183 5.32E-16
1696 ILMN_ .1685022 23473 CAPN7 -0.294 6.75E-04 0.286 4.89E-04
1697 ILMN_ .1685056 23769 FLRT1 -0.232 7.25E-03 0.626 6.85E-09
1698 ILMN_ .1685124 79600 TCTN1 -0.529 1.28E-07 0.275 1.33E-03
1699 ILMN_ .1685258 81853 TMEM14B -0.649 4.44E-09 0.334 1.32E-04
1700 ILMN_ .1685289 64755 C16orf58 -0.677 3.16E-10 0.767 2.26E-11
1701 ILMN_ .1685608 4885 NPTX2 -0.574 1.61E-08 2.091 1.44E-22
1702 ILMN_ .1685625 7351 UCP2 -1.263 1.72E-15 0.668 4.48E-09
1703 ILMN_ .1685636 3781 KCNN2 -0.440 1.36E-05 0.321 4.18E-04
1704 ILMN_ .1685703 8309 ACOX2 -0.469 3.27E-06 0.393 4.20E-05
1705 ILMN_ .1685781 84520 C14orfl42 -0.254 5.44E-03 0.308 1.17E-03
1706 ILMN_ .1685854 492311 C5orf53 -0.804 1.92E-09 0.394 2.06E-04
1707 ILMN_ .1685928 89891 WDR34 -1.075 1.23E-12 0.736 5.31E-09
1708 ILMN_ .1686082 122616 C14orf79 -0.367 8.69E-05 0.452 5.15E-06
1709 ILMN_ .1686194 10283 SDCCAG10 -0.864 9.87E-12 0.220 8.44E-03
1710 ILMN_ .1686319 57695 USP37 -0.471 8.77E-07 0.566 5.06E-08
1711 ILMN_ .1686392 51594 NBAS -0.317 2.97E-04 0.346 1.12E-04
1712 ILMN_ .1686454 92610 TIFA -0.286 6.37E-04 0.290 7.47E-04
1713 ILMN_ .1686458 22995 CEP152 -0.908 2.80E-11 0.392 5.57E-05
1714 ILMN_ .1686513 389734 CNTNAP3B -0.345 1.53E-03 0.297 7.39E-04
1715 ILMN_ .1687107 55159 RFWD3 -0.716 3.27E-10 0.516 1.85E-07 1716 ILMN_ .1687247 64847 SPATA20 -0.350 5.83E-05 0.483 7.33E-07
1717 ILMN_ .1687303 80724 ACAD 10 -0.486 4.27E-05 0.318 2.24E-03
1718 ILMN_ .1687315 6256 RXRA -0.779 7.22E-10 0.809 3.99E-10
1719 ILMN_ .1687508 501 ALDH7A1 -0.342 1.86E-04 0.778 2.32E-10
1720 ILMN_ .1687864 51367 POP5 -0.666 2.96E-09 0.225 8.30E-03
1721 ILMN_ .1688031 145483 FAM161B -0.389 2.66E-04 0.358 2.67E-04
1722 ILMN_ .1688103 56998 CTNNBIP1 -1.332 2.73E-13 0.480 7.06E-05
1723 ILMN_ .1688160 253769 WDR27 -0.914 7.98E-11 0.552 1.41E-06
1724 ILMN_ .1688246 642852 LOC642852 -0.565 1.05E-07 0.426 1.17E-05
1725 ILMN_ .1688455 23078 KIAA0564 -0.410 7.69E-05 0.277 3.83E-03
1726 ILMN_ .1688464 79929 MAP6D1 -0.717 5.11E-10 0.345 1.46E-04
1727 ILMN_ .1688621 58493 C9orf80 -0.847 2.02E-11 0.272 1.52E-03
1728 ILMN_ .1688848 93109 TMEM44 -0.491 3.31E-07 0.548 7.59E-08
1729 ILMN_ .1688853 221504 ZBTB9 -0.298 5.02E-04 0.232 4.82E-03
1730 ILMN_ .1689070 10229 COQ7 -0.598 8.96E-09 0.228 5.74E-03
1731 ILMN_ .1689327 730534 LOC730534 -0.424 3.25E-06 0.378 1.15E-05
1732 ILMN_ .1689329 6319 SCD -0.496 5.21E-07 0.244 3.31E-03
1733 ILMN_ .1689336 3206 HOXA10 -0.358 2.52E-04 0.265 4.67E-03
1734 ILMN_ .1689712 440927 LOC440927 -0.386 1.78E-05 0.238 3.51E-03
1735 ILMN_ .1689774 114932 MRFAP1L1 -0.229 2.62E-03 0.378 1.19E-05
1736 ILMN_ .1690040 7108 TM7SF2 -0.666 5.01E-09 0.467 1.70E-06
1737 ILMN_ .1690282 8738 CRADD -0.225 8.15E-03 0.387 3.86E-05
1738 ILMN_ .1690342 4048 LTA4H -0.755 1.20E-11 0.789 4.10E-12
1739 ILMN_ .1690392 23412 COMMD3 -1.481 3.29E-18 1.243 2.60E-16
1740 ILMN_ .1690420 2672 GFI1 -1.418 1.07E-17 0.341 9.03E-05
1741 ILMN_ .1690454 389119 C3orf54 -1.572 1.12E-16 0.506 4.42E-06
1742 ILMN_ .1690523 55222 LRRC20 -1.251 1.32E-14 0.613 5.53E-08
1743 ILMN_ .1690610 22913 RALY -0.387 1.15E-05 0.380 2.20E-05
1744 ILMN_ .1690653 10263 CDK2AP2 -0.462 1.40E-05 0.362 2.64E-04
1745 ILMN_ .1690806 201562 PTPLB -1.039 5.35E-13 0.624 4.52E-09
1746 ILMN_ .1690807 57496 MKL2 -0.523 2.61E-06 0.405 6.81E-05
1747 ILMN_ .1690982 1652 DDT -0.473 3.13E-07 0.227 4.50E-03
1748 ILMN_ .1691165 63967 CLSPN -0.535 9.18E-08 0.471 1.04E-06
1749 ILMN_ .1691180 5013 OTX1 -0.734 2.69E-11 0.425 1.24E-06
1750 ILMN_ .1691188 51720 UIMC1 -0.321 5.45E-05 0.218 4.06E-03
1751 ILMN_ .1691276 30827 CXXC1 -0.772 2.08E-11 0.204 8.29E-03
1752 ILMN_ .1691430 79807 GSTCD -0.541 7.97E-08 0.229 6.10E-03
1753 ILMN_ 1691444 115426 UHRF2 -0.821 5.22E-11 0.475 1.29E-06
1754 ILMN_ .1691567 132789 GNPDA2 -0.223 8.74E-03 0.641 8.75E-09
1755 ILMN_ .1691572 7263 TST -1.017 1.32E-14 0.913 2.48E-13
1756 ILMN_ .1691747 10656 KHDRBS3 -0.290 6.45E-03 1.227 6.21E-13
1757 ILMN_ .1691949 728554 LOC728554 -0.617 7.27E-10 0.213 4.24E-03
1758 ILMN_ .1691966 400579 FLJ35934 -0.324 7.74E-04 0.284 3.07E-03
1759 ILMN_ .1691980 84668 FAM126A -0.265 3.86E-03 0.438 4.02E-06 1760 ILMN_ .1692072 728006 LOC728006 -0.237 3.51E-03 0.231 4.02E-03
1761 ILMN_ .1692219 80223 RAB11FIP1 -1.336 2.05E-16 0.758 1.79E-10
1762 ILMN_ .1692511 79022 TMEM106C -1.706 1.24E-16 1.468 3.98E-15
1763 ILMN_ .1692706 55208 DCUN1D2 -0.302 3.24E-04 0.228 5.47E-03
1764 ILMN_ .1692790 23421 ITGB3BP -0.850 1.23E-11 0.643 5.71E-09
1765 ILMN_ .1692938 29968 PS ATI -0.814 3.03E-10 1.789 1.41E-18
1766 ILMN_ .1693466 79874 RABEP2 -0.291 1.13E-03 0.395 3.43E-05
1767 ILMN_ .1693766 9662 CEP135 -0.485 2.64E-06 0.607 7.91E-08
1768 ILMN_ .1694027 143686 SESN3 -1.699 9.84E-18 0.593 2.52E-07
1769 ILMN_ .1694075 1647 GADD45A -0.211 1.13E-02 1.914 2.61E-20
1770 ILMN_ .1694106 23171 GPD1L -1.119 9.12E-15 0.271 1.29E-03
1771 ILMN_ .1694111 11284 PNKP -0.555 2.97E-08 0.539 5.61E-08
1772 ILMN_ .1694126 347240 KIF24 -0.962 7.05E-12 0.777 9.44E-10
1773 ILMN_ .1694177 5111 PCNA -0.882 6.04E-12 0.517 2.82E-07
1774 ILMN_ .1694233 97 ACYP1 -0.821 1.41E-11 0.721 3.87E-10
1775 ILMN_ .1694268 55502 HES6 -1.218 2.88E-15 0.984 4.19E-13
1776 ILMN_ .1694325 4784 NFIX -0.219 1.04E-02 0.343 2.28E-04
1777 ILMN_ 1694491 900 CCNG1 -0.359 3.02E-05 0.510 1.30E-07
1778 ILMN_ .1694708 650737 LOC650737 -0.218 9.25E-03 0.305 6.79E-04
1779 ILMN_ .1694759 79086 C19orf42 -0.298 7.43E-04 0.245 3.28E-03
1780 ILMN_ 1694840 4147 MATN2 -1.182 2.11E-14 1.347 6.37E-16
1781 ILMN_ .1694983 11218 DDX20 -0.223 8.89E-03 0.259 1.25E-03
1782 ILMN_ .1695092 7485 WRB -1.088 7.06E-13 0.455 6.78E-06
1783 ILMN_ .1695276 10982 MAPRE2 -0.563 7.95E-08 0.239 4.99E-03
1784 ILMN_ .1695334 90780 PYG02 -0.577 1.61E-06 0.476 1.86E-05
1785 ILMN_ .1695356 115992 RNF166 -0.258 4.40E-03 0.268 3.67E-03
1786 ILMN_ .1695386 5889 RAD51C -0.770 1.76E-11 0.330 7.68E-05
1787 ILMN_ .1695413 353088 ZNF429 -0.367 1.47E-04 0.599 5.33E-08
1788 ILMN_ .1695414 55723 ASF1B -1.068 3.34E-14 1.373 8.82E-17
1789 ILMN_ .1695645 1069 CETN2 -0.516 1.02E-07 0.425 3.70E-06
1790 ILMN_ .1695731 7283 TUBG1 -0.695 1.76E-10 0.606 3.77E-09
1791 ILMN_ .1695821 10120 ACTR1B -0.638 2.26E-09 0.649 1.92E-09
1792 ILMN_ .1695946 388610 TRNP1 -0.397 2.09E-05 0.526 3.71E-07
1793 ILMN_ .1695959 59271 C21orf63 -0.324 1.08E-03 0.271 2.65E-03
1794 ILMN_ .1696254 124936 CYB5D2 -0.428 4.41E-06 0.340 1.46E-04
1795 ILMN_ .1696266 7517 XRCC3 -0.655 8.71E-08 0.449 4.09E-05
1796 ILMN_ .1696339 7546 ZIC2 -0.668 6.07E-10 0.663 9.69E-10
1797 ILMN_ .1696375 64427 TTC31 -0.362 1.16E-04 0.297 1.14E-03
1798 ILMN_ .1696469 648509 LOC648509 -1.167 3.46E-12 0.374 4.85E-04
1799 ILMN_ .1696699 79632 FAM184A -0.952 1.75E-11 0.646 4.00E-08
1800 ILMN_ .1696827 25973 PARS2 -0.382 2.87E-05 0.331 2.38E-04
1801 ILMN_ .1696843 613037 LOC613037 -0.508 3.92E-06 0.445 1.37E-05
1802 ILMN_ .1696975 7398 USP1 -0.882 1.98E-12 0.753 2.85E-11
1803 ILMN_ .1697006 642361 LOC642361 -0.203 1.24E-02 0.425 4.82E-06 1804 ILMN_ .1697095 440423 SUZ12P -0.412 1.47E-05 0.298 9.19E-04
1805 ILMN_ .1697412 57127 RHBG -0.572 4.54E-06 0.302 1.92E-03
1806 ILMN_ .1697548 23266 LPHN2 -0.897 9.77E-13 0.440 1.51E-06
1807 ILMN_ .1697820 84681 HINT2 -0.665 1.58E-09 1.137 6.26E-15
1808 ILMN_ .1697962 197370 NSMCE1 -0.220 4.96E-03 0.280 8.02E-04
1809 ILMN_ .1698164 641693 LOC641693 -0.284 2.58E-03 0.243 8.39E-03
1810 ILMN_ .1698185 197335 WDR90 -1.332 1.53E-15 0.441 8.84E-06
1811 ILMN_ .1698191 10389 SCML2 -0.752 3.87E-11 0.380 1.75E-05
1812 ILMN_ .1698252 2187 FANCB -0.562 2.18E-07 0.467 5.66E-06
1813 ILMN_ .1698491 53615 MBD3 -0.591 1.43E-08 0.231 5.54E-03
1814 ILMN_ .1698677 54969 C4orf27 -0.355 1.06E-04 0.305 6.49E-04
1815 ILMN_ .1698766 29108 PYCARD -0.889 1.14E-12 0.255 1.92E-03
1816 ILMN_ .1699208 4673 NAP1L1 -0.509 5.16E-07 0.441 7.01E-06
1817 ILMN_ .1699451 401218 LOC401218 -0.524 6.17E-07 0.432 9.80E-06
1818 ILMN_ .1699472 6487 ST3GAL3 -0.583 1.68E-07 0.273 3.47E-03
1819 ILMN_ .1699521 57730 KIAA1641 -1.270 1.14E-13 0.631 1.11E-07
1820 ILMN_ .1699623 145773 FAM81A -0.458 3.22E-05 0.304 2.43E-03
1821 ILMN_ 1699644 115123 Mar-03 -0.686 1.47E-09 0.594 2.35E-08
1822 ILMN_ .1700042 83660 TLN2 -0.408 2.32E-05 0.596 4.85E-08
1823 ILMN_ .1700306 132299 OCIAD2 -0.243 2.42E-03 0.696 5.28E-10
1824 ILMN_ .1700515 284018 C17orf58 -0.491 1.12E-06 0.337 2.82E-04
1825 ILMN_ .1700690 10493 VAT1 -0.548 3.13E-07 0.451 8.66E-06
1826 ILMN_ .1700695 23446 SLC44A1 -1.165 1.48E-14 0.468 2.80E-06
1827 ILMN_ .1700915 648 BMI1 -0.948 1.85E-13 0.372 1.80E-05
1828 ILMN_ .1700955 255758 TCTEX1D2 -1.236 1.43E-15 0.847 1.39E-11
1829 ILMN_ .1701025 2052 EPHX1 -0.243 6.65E-03 1.130 6.97E-14
1830 ILMN_ .1701386 55437 STRADB -0.790 2.84E-10 0.612 6.76E-08
1831 ILMN_ .1701413 9091 PIGQ -0.476 9.97E-07 0.656 3.68E-09
1832 ILMN_ .1701461 7078 TIMP3 -0.538 1.35E-06 0.682 1.88E-08
1833 ILMN_ .1701643 81544 GDPD5 -0.481 5.62E-07 0.492 4.41E-07
1834 ILMN_ .1701711 10902 BRD8 -0.734 1.34E-10 0.256 1.78E-03
1835 ILMN_ .1701731 231 AKR1B1 -0.385 1.52E-05 0.576 2.67E-08
1836 ILMN_ .1702124 222484 LNX2 -0.233 5.90E-03 0.346 1.67E-04
1837 ILMN_ .1702171 79888 LPCAT1 -0.538 1.92E-07 0.385 1.95E-05
1838 ILMN_ .1702247 23582 CCNDBP1 -0.254 1.84E-03 0.296 5.70E-04
1839 ILMN_ .1702265 84064 HDHD2 -0.236 5.70E-03 0.255 2.44E-03
1840 ILMN_ .1702447 10644 IGF2BP2 -0.635 9.09E-10 0.245 1.49E-03
1841 ILMN_ .1703074 1362 CPD -0.479 3.47E-07 0.706 8.51E-11
1842 ILMN_ .1703092 9401 RECQL4 -1.377 2.93E-16 0.615 2.57E-08
1843 ILMN_ .1703279 55086 CXorf57 -0.758 1.07E-11 1.161 5.72E-16
1844 ILMN_ .1703316 255783 LOC255783 -0.279 8.87E-04 1.207 1.99E-15
1845 ILMN_ .1703408 7976 FZD3 -0.622 2.27E-08 0.256 1.36E-03
1846 ILMN_ .1703435 26149 ZNF658 -1.007 1.71E-14 0.573 9.88E-09
1847 ILMN_ .1703531 1903 S1PR3 -0.358 3.63E-04 0.413 5.82E-05 1848 ILMN_ .1703565 29997 GLTSCR2 -0.460 3.01E-06 0.579 7.29E-08
1849 ILMN_ .1703593 55971 BAIAP2L1 -0.306 1.78E-03 0.399 1.31E-04
1850 ILMN_ .1703683 25839 COG4 -0.645 5.79E-08 0.391 8.32E-05
1851 ILMN_ .1704091 8694 DGAT1 -1.004 6.84E-14 0.553 3.10E-08
1852 ILMN_ .1704353 3321 IGSF3 -0.476 2.41E-06 0.366 7.87E-05
1853 ILMN_ .1704431 554203 LOC554203 -0.298 2.43E-04 0.253 1.45E-03
1854 ILMN_ .1704537 26227 PHGDH -0.977 9.36E-13 2.360 1.38E-22
1855 ILMN_ .1704672 79035 OBFC2B -0.763 4.91E-11 0.239 3.62E-03
1856 ILMN_ .1704753 2034 EPAS1 -0.749 1.59E-10 0.645 4.76E-09
1857 ILMN_ .1705390 84861 KLHL22 -0.339 1.36E-04 0.485 6.41E-07
1858 ILMN_ .1705458 25893 TRIM58 -0.592 7.80E-08 0.290 1.73E-03
1859 ILMN_ .1705570 55506 H2AFY2 -0.294 5.73E-04 0.672 5.01E-10
1860 ILMN_ .1705679 9667 SAFB2 -0.346 1.48E-04 0.523 4.89E-07
1861 ILMN_ .1705686 4900 NRGN -1.720 3.19E-17 1.403 3.36E-15
1862 ILMN_ .1705737 3615 IMPDH2 -1.223 2.52E-15 0.635 7.80E-09
1863 ILMN_ .1706015 131583 FAM43A -0.795 3.33E-10 0.536 6.71E-07
1864 ILMN_ .1706094 25831 HECTD1 -0.663 4.09E-09 0.284 1.36E-03
1865 ILMN_ .1706266 114804 RNF157 -0.374 3.44E-04 0.354 6.20E-04
1866 ILMN_ .1706326 9553 MRPL33 -0.592 5.87E-09 0.268 1.02E-03
1867 ILMN_ .1706660 81888 HYI -1.319 6.22E-14 0.413 1.98E-04
1868 ILMN_ .1706764 55204 GOLPH3L -0.425 3.17E-06 0.775 4.08E-11
1869 ILMN_ .1706779 3978 LIG1 -1.415 2.41E-15 0.858 3.03E-10
1870 ILMN_ .1706886 605 BCL7A -0.457 1.01E-05 0.281 2.60E-03
1871 ILMN_ .1706959 29928 TIMM22 -0.579 1.29E-08 0.421 4.80E-06
1872 ILMN_ .1707685 730302 LOC730302 -1.090 2.99E-14 0.737 2.79E-10
1873 ILMN_ .1707720 6510 SLC1A5 -0.293 1.70E-03 0.499 2.17E-06
1874 ILMN_ .1707763 7982 ST7 -0.315 7.91E-04 0.413 2.96E-05
1875 ILMN_ .1707858 3015 H2AFZ -0.358 9.22E-05 0.351 1.11E-04
1876 ILMN_ .1708009 55915 LANCL2 -0.245 6.39E-03 0.558 2.91E-07
1877 ILMN_ .1708016 116151 C20orfl08 -0.392 6.91E-05 0.330 4.39E-04
1878 ILMN_ .1708105 2146 EZH2 -0.587 3.56E-09 0.378 9.17E-06
1879 ILMN_ .1708151 8270 LAGE3 -0.951 6.43E-14 0.485 1.85E-07
1880 ILMN_ .1708382 54859 C3orf75 -0.793 1.19E-11 0.446 1.37E-06
1881 ILMN_ .1708482 283232 TMEM80 -0.710 1.43E-09 0.313 6.17E-04
1882 ILMN_ .1708508 22843 PPM1E -0.208 1.01E-02 0.503 3.90E-07
1883 ILMN_ .1708672 39 ACAT2 -0.633 1.01E-07 0.279 4.37E-03
1884 ILMN_ .1708798 55840 EAF2 -0.513 2.95E-07 0.367 6.36E-05
1885 ILMN_ .1708907 644890 MEIG1 -0.277 5.82E-03 0.383 1.95E-04
1886 ILMN_ .1709020 4605 MYBL2 -0.723 5.25E-09 0.361 3.67E-05
1887 ILMN_ .1709237 2053 EPHX2 -0.746 2.73E-10 0.725 7.56E-10
1888 ILMN_ .1709307 26086 GPSM1 -0.272 1.59E-03 0.713 9.70E-10
1889 ILMN_ 1709474 7840 ALMS1 -0.383 9.11E-05 0.250 6.74E-03
1890 ILMN_ .1709483 4361 MRE11A -0.697 2.00E-10 0.358 4.02E-05
1891 ILMN_ _1709484 641 BLM -1.143 2.17E-15 0.340 8.24E-05 1892 ILMN_ .1710000 92960 PEX11G -0.298 6.25E-04 0.671 2.25E-09
1893 ILMN_ .1710207 55719 C10orf6 -0.626 1.56E-09 0.609 2.90E-09
1894 ILMN_ .1710434 374403 TBC1D10C -0.514 1.11E-05 0.366 4.56E-04
1895 ILMN_ .1710495 89932 PAPLN -0.612 2.08E-08 0.535 2.94E-07
1896 ILMN_ .1710676 26271 FBX05 -1.115 2.07E-14 0.660 3.30E-09
1897 ILMN_ .1711005 993 CDC25A -0.774 3.30E-11 0.296 4.63E-04
1898 ILMN_ .1711208 1952 CELSR2 -0.901 3.43E-12 0.480 1.21E-06
1899 ILMN_ .1711368 83696 TRAPPC9 -0.394 2.94E-05 0.392 4.15E-05
1900 ILMN_ .1711470 29089 UBE2T -0.830 5.24E-12 0.792 2.41E-11
1901 ILMN_ .1711493 84106 PRAM1 -0.395 3.69E-04 0.645 5.41E-08
1902 ILMN_ .1711514 1690 COCH -0.479 1.12E-06 1.032 2.13E-13
1903 ILMN_ .1711608 23635 SSBP2 -0.656 1.11E-09 0.817 1.41E-11
1904 ILMN_ .1711799 55071 C9orf40 -1.096 2.10E-15 0.833 1.73E-12
1905 ILMN_ .1711904 83463 MXD3 -1.389 2.55E-16 0.221 8.75E-03
1906 ILMN_ .1711988 56660 KCNK12 -0.360 1.93E-04 0.452 5.54E-06
1907 ILMN_ .1712075 23336 SYNM -0.679 5.08E-10 1.064 1.04E-14
1908 ILMN_ .1712298 157567 ANKRD46 -0.454 1.37E-05 0.646 2.38E-08
1909 ILMN_ .1712320 79009 DDX50 -0.319 3.57E-04 0.306 4.65E-04
1910 ILMN_ .1712386 54069 C21orf45 -1.003 3.68E-13 0.237 5.82E-03
1911 ILMN_ .1712389 51192 CKLF -0.530 5.67E-08 0.535 4.49E-08
1912 ILMN_ .1712413 116832 RPL39L -0.775 5.38E-11 0.596 6.22E-09
1913 ILMN_ .1712469 23015 GOLGA8A -0.376 3.68E-04 0.429 3.29E-05
1914 ILMN_ .1712487 1939 LGTN -0.360 3.71E-05 0.443 2.78E-06
1915 ILMN_ .1712583 79006 METRN -0.562 2.47E-06 0.269 8.62E-03
1916 ILMN_ .1712636 4931 NVL -0.477 1.28E-06 0.583 5.37E-08
1917 ILMN_ .1712678 51065 RPS27L -0.789 9.55E-12 0.551 1.20E-08
1918 ILMN_ .1712773 6674 SPAG1 -0.501 3.24E-05 0.635 9.06E-08
1919 ILMN_ .1712786 23382 AHCYL2 -0.582 1.01E-07 0.490 8.97E-07
1920 ILMN_ .1713129 7270 TTF1 -0.315 1.03E-03 0.228 7.86E-03
1921 ILMN_ .1713189 54934 C12orf41 -0.301 1.42E-04 0.298 2.27E-04
1922 ILMN_ .1713402 84067 FAM160A2 -0.354 9.65E-05 0.314 2.67E-04
1923 ILMN_ .1713454 79891 ZNF671 -0.325 2.05E-04 0.626 8.34E-09
1924 ILMN_ .1713764 440928 LOC440928 -0.998 3.98E-12 0.280 3.14E-03
1925 ILMN_ .1713803 400566 C17orf97 -0.619 3.11E-09 0.239 2.74E-03
1926 ILMN_ .1713807 57134 MAN1C1 -0.352 3.59E-05 0.276 8.37E-04
1927 ILMN_ .1713901 11015 KDELR3 -0.493 2.19E-06 0.674 6.49E-09
1928 ILMN_ .1713964 22903 BTBD3 -0.405 5.36E-05 0.270 3.56E-03
1929 ILMN_ .1713985 84232 MAF1 -0.285 4.39E-03 0.365 3.32E-04
1930 ILMN_ .1714167 1528 CYB5A -0.243 9.77E-04 0.448 4.77E-07
1931 ILMN_ .1714384 5095 PCCA -0.356 1.51E-04 0.290 1.63E-03
1932 ILMN_ .1714419 79173 C19orf57 -0.281 3.33E-04 0.219 4.70E-03
1933 ILMN_ .1714438 4595 MUTYH -0.620 1.40E-08 0.892 8.62E-12
1934 ILMN_ .1714765 389599 LOC389599 -0.787 1.05E-10 0.383 4.82E-05
1935 ILMN_ .1715569 51019 CCDC53 -0.439 2.07E-06 0.447 2.02E-06 1936 ILMN_ .1715625 128710 C20orf94 -0.466 6.15E-06 0.251 6.49E-03
1937 ILMN_ .1715823 157574 FBX016 -0.371 l.OOE-03 0.261 8.98E-03
1938 ILMN_ .1715905 79980 DSN1 -0.990 1.17E-11 0.767 2.52E-09
1939 ILMN_ .1715908 29781 NCAPH2 -0.901 4.00E-13 0.555 2.03E-08
1940 ILMN_ .1716006 162681 C18orf54 -0.636 7.55E-09 0.441 3.93E-06
1941 ILMN_ .1716089 25959 KANK2 -0.881 1.58E-11 0.506 6.94E-07
1942 ILMN_ .1716093 3858 KRT10 -0.495 2.61E-07 0.660 1.13E-09
1943 ILMN_ .1716105 91662 NLRP12 -0.292 4.34E-03 1.863 1.13E-18
1944 ILMN_ .1716157 55833 UBAP2 -0.525 1.56E-07 0.255 2.77E-03
1945 ILMN_ .1716368 201973 CCDC111 -0.530 4.62E-06 0.461 3.59E-05
1946 ILMN_ .1716382 387882 LOC387882 -0.659 5.86E-09 0.651 6.32E-09
1947 ILMN_ .1716480 65057 ACD -0.766 1.80E-09 0.411 7.56E-05
1948 ILMN_ .1716766 1054 CEBPG -0.745 2.06E-10 1.206 2.98E-15
1949 ILMN_ .1716895 6119 RPA3 -0.907 2.07E-13 0.833 2.27E-12
1950 ILMN_ .1717219 84792 C7orf70 -0.392 3.10E-05 0.467 3.00E-06
1951 ILMN_ .1717294 5774 PTPN3 -0.389 1.74E-05 0.354 3.93E-05
1952 ILMN_ .1717707 118672 PSTK -0.244 3.52E-03 0.228 4.86E-03
1953 ILMN_ .1717727 284293 LOC284293 -0.378 7.75E-04 0.395 6.47E-05
1954 ILMN_ .1718071 23287 AGTPBP1 -0.681 1.03E-09 0.300 5.60E-04
1955 ILMN_ .1718336 84310 C7orf50 -1.028 6.18E-15 0.394 4.37E-06
1956 ILMN_ .1718621 10077 TSPAN32 -2.137 7.25E-21 0.432 1.01E-05
1957 ILMN_ .1718646 4324 MMP15 -0.687 7.91E-08 0.249 5.32E-03
1958 ILMN_ .1718771 149473 CCDC24 -0.298 1.31E-03 0.453 8.64E-06
1959 ILMN_ .1718907 10194 TSHZ1 -0.450 1.11E-06 0.268 1.28E-03
1960 ILMN_ .1718960 5271 SERPWB8 -0.851 2.86E-12 0.209 6.69E-03
1961 ILMN_ .1719032 27258 LSM3 -0.773 1.15E-10 0.306 4.52E-04
1962 ILMN_ .1719224 125144 C17orf45 -0.870 7.11E-11 0.476 2.25E-06
1963 ILMN_ .1719256 1163 CKS1B -0.453 1.28E-06 0.454 1.74E-06
1964 ILMN_ .1719616 1773 DNASE1 -0.317 4.36E-03 0.363 3.56E-04
1965 ILMN_ .1719876 84451 KIAA1804 -0.743 4.93E-10 0.236 3.37E-03
1966 ILMN_ .1719906 3033 HADH -1.307 1.16E-15 0.813 2.87E-11
1967 ILMN_ .1720235 122622 ADSSL1 -0.853 6.76E-12 0.485 7.58E-07
1968 ILMN_ .1720266 91431 LOC91431 -0.768 1.06E-09 0.678 8.94E-09
1969 ILMN_ .1720270 1039 CDR2 -0.519 1.51E-06 0.295 1.88E-03
1970 ILMN_ .1720844 117178 SSX2IP -0.814 3.48E-10 0.368 1.19E-04
1971 ILMN_ .1720857 387036 GUSBL1 -0.571 1.83E-07 0.440 8.21E-06
1972 ILMN_ .1720941 2121 EVC -0.321 8.18E-04 0.344 4.19E-04
1973 ILMN_ .1721115 645743 LOC645743 -0.203 1.19E-02 0.235 2.89E-03
1974 ILMN_ .1722059 6294 SAFB -0.325 1.09E-04 0.273 7.49E-04
1975 ILMN_ .1722127 25788 RAD54B -0.903 6.71E-13 0.673 7.59E-10
1976 ILMN_ .1722239 1678 TIMM8A -0.538 9.47E-08 0.308 3.96E-04
1977 ILMN_ .1722294 144402 CPNE8 -0.243 3.37E-03 0.293 6.48E-04
1978 ILMN_ .1722533 84056 KATNAL1 -0.404 7.38E-05 0.469 8.26E-06
1979 ILMN_ .1722726 9743 RICS -0.611 6.85E-09 0.498 2.94E-07 1980 ILMN_ .1722798 113026 PLCD3 -0.212 1.26E-02 0.422 1.37E-05
1981 ILMN_ .1722834 6002 RGS12 -1.040 4.66E-13 0.505 1.04E-06
1982 ILMN_ .1722905 64963 MRPS11 -0.225 3.87E-03 0.351 4.32E-05
1983 ILMN_ .1722985 401509 ZNF658B -0.467 2.03E-06 0.262 2.18E-03
1984 ILMN_ .1723021 23463 ICMT -0.777 5.18E-10 0.439 8.35E-06
1985 ILMN_ .1723116 267 AMFR -0.379 6.17E-04 0.247 4.51E-03
1986 ILMN_ .1723123 2261 FGFR3 -0.733 1.27E-08 2.157 1.40E-20
1987 ILMN_ .1723418 1056 CEL -0.556 2.92E-07 0.354 1.59E-04
1988 ILMN_ .1723522 81575 APOLD1 -0.410 2.62E-04 0.860 2.88E-10
1989 ILMN_ .1723768 79671 NLRX1 -0.935 3.06E-12 0.351 1.62E-04
1990 ILMN_ .1723793 79728 PALB2 -0.270 6.73E-04 0.233 3.12E-03
1991 ILMN_ .1723935 645362 LOC645362 -0.287 6.07E-04 0.365 4.85E-05
1992 ILMN_ .1724437 23464 GCAT -0.863 5.88E-12 0.315 3.42E-04
1993 ILMN_ .1724489 5984 RFC4 -0.766 2.51E-11 0.660 6.65E-10
1994 ILMN_ .1724495 91404 SESTD1 -0.247 1.18E-03 0.320 8.43E-05
1995 ILMN_ .1724598 11159 RABL2A -0.364 1.17E-03 0.419 2.16E-04
1996 ILMN_ .1724753 51199 NIN -0.646 2.11E-09 0.387 2.06E-05
1997 ILMN_ .1724832 58495 OVOL2 -1.610 1.36E-16 0.661 8.19E-08
1998 ILMN_ .1725166 353497 POLN -0.247 7.11E-03 0.582 1.92E-07
1999 ILMN_ .1725188 5584 PRKCI -0.391 2.04E-04 0.341 9.01E-04
2000 ILMN_ .1725193 3485 IGFBP2 -0.782 1.24E-10 0.444 3.69E-06
2001 ILMN_ .1725620 79893 GGNBP2 -0.292 2.81E-04 0.235 3.20E-03
2002 ILMN_ .1725679 169270 ZNF596 -0.299 2.32E-03 0.289 2.44E-03
2003 ILMN_ .1725787 5989 RFX1 -0.232 1.02E-02 0.613 8.24E-08
2004 ILMN_ .1725791 9200 PTPLA -0.877 2.12E-11 0.375 4.35E-05
2005 ILMN_ .1726030 2882 GPX7 -0.632 1.54E-08 0.299 8.96E-04
2006 ILMN_ .1726288 54664 TMEM106B -0.429 7.92E-05 0.277 4.17E-03
2007 ILMN_ .1726512 54993 ZSCAN2 -0.462 3.72E-06 0.328 2.84E-04
2008 ILMN_ .1726565 5296 PIK3R2 -0.642 2.79E-10 0.491 9.46E-08
2009 ILMN_ .1726711 5179 PENK -0.813 2.51E-10 0.251 5.96E-03
2010 ILMN_ .1726928 6920 TCEA3 -0.591 1.76E-07 0.356 4.61E-05
2011 ILMN_ .1726986 51166 AADAT -0.306 4.32E-03 0.305 2.40E-03
2012 ILMN_ .1727073 4201 MEA1 -0.279 9.29E-04 0.882 4.48E-12
2013 ILMN_ .1727134 57542 KLHDC5 -0.308 9.49E-04 0.254 5.87E-03
2014 ILMN_ .1727142 3551 1KB KB -0.294 3.46E-04 0.326 1.08E-04
2015 ILMN_ .1727540 55732 Clorfl l2 -1.023 5.18E-13 0.667 7.38E-09
2016 ILMN_ .1727553 63920 C5orf54 -0.630 3.00E-09 0.684 2.51E-10
2017 ILMN_ .1727692 54802 TRIT1 -0.368 8.95E-04 0.273 6.64E-03
2018 ILMN_ .1727738 83452 RAB33B -0.259 8.86E-03 0.742 1.11E-08
2019 ILMN_ .1727813 25874 BRP44 -1.012 2.22E-13 1.050 1.01E-13
2020 ILMN_ .1728083 1979 EIF4EBP2 -0.526 6.30E-08 0.408 6.55E-06
2021 ILMN_ .1728107 2788 GNG7 -1.021 1.67E-14 0.261 6.64E-04
2022 ILMN_ .1728199 5426 POLE -1.115 3.91E-13 0.484 3.44E-06
2023 ILMN_ .1728228 147694 ZNF548 -0.223 1.06E-02 0.464 1.67E-06 2024 ILMN_ .1728380 493911 PHOSPH02 -0.497 4.94E-06 0.728 5.36E-09
2025 ILMN_ .1728471 10565 ARFGEF1 -0.372 2.52E-05 0.264 1.61E-03
2026 ILMN_ .1728498 57060 PCBP4 -0.713 5.67E-09 0.466 9.49E-06
2027 ILMN_ .1728512 7533 YWHAH -0.444 2.16E-06 0.368 4.37E-05
2028 ILMN_ .1728605 7267 TTC3 -0.743 1.19E-10 0.421 5.82E-06
2029 ILMN_ .1728698 51573 GDE1 -0.513 7.52E-08 0.271 9.14E-04
2030 ILMN_ .1728779 55768 NGLY1 -0.251 5.55E-03 0.423 3.04E-05
2031 ILMN_ .1729051 2956 MSH6 -0.874 2.41E-12 0.737 1.80E-10
2032 ILMN_ .1729112 56994 CHPT1 -0.595 2.14E-07 0.615 6.03E-08
2033 ILMN_ .1729374 2109 ETFB -0.770 1.38E-08 0.598 7.02E-07
2034 ILMN_ .1729533 128240 APOA1BP -0.996 6.59E-14 0.371 1.61E-05
2035 ILMN_ .1729650 5191 PEX7 -0.364 3.03E-05 0.412 6.53E-06
2036 ILMN_ .1729976 283489 ZNF828 -0.685 1.63E-09 0.405 1.93E-05
2037 ILMN_ .1730048 79034 C7orf26 -0.308 1.42E-04 0.492 2.10E-07
2038 ILMN_ .1730201 1837 DTNA -0.370 6.73E-05 0.377 6.01E-05
2039 ILMN_ .1730260 221143 N6AMT2 -0.745 3.42E-10 0.406 2.19E-05
2040 ILMN_ .1730631 80304 C2orf44 -0.460 6.81E-07 0.361 3.79E-05
2041 ILMN_ .1730639 55356 SLC22A15 -0.414 3.03E-05 0.698 1.93E-09
2042 ILMN_ .1730879 25776 CBY1 -0.591 1.55E-09 0.814 2.11E-12
2043 ILMN_ .1730907 79752 ZFAND1 -0.365 5.10E-05 0.317 3.84E-04
2044 ILMN_ .1730928 8851 CDK5R1 -1.123 6.54E-15 0.502 3.68E-07
2045 ILMN_ .1730999 7175 TPR -0.596 8.22E-08 0.243 7.02E-03
2046 ILMN_ .1731070 23594 ORC6L -0.560 2.02E-06 0.548 1.80E-06
2047 ILMN_ .1731157 58529 MYOZ1 -0.435 1.85E-06 0.752 6.25E-11
2048 ILMN_ .1731184 9833 MELK -0.407 2.48E-06 0.313 1.56E-04
2049 ILMN_ .1731206 85409 NKD2 -1.580 2.74E-18 0.736 3.54E-10
2050 ILMN_ .1731237 64084 CLSTN2 -1.584 2.03E-19 0.781 5.56E-12
2051 ILMN_ .1731349 3209 HOXA13 -0.868 6.57E-09 0.311 5.28E-03
2052 ILMN_ .1731374 1363 CPE -0.317 3.72E-04 0.979 1.04E-12
2053 ILMN_ .1731561 64221 ROB03 -0.540 7.76E-07 0.717 4.22E-09
2054 ILMN_ .1731745 4815 NINJ2 -0.717 3.02E-10 0.236 4.39E-03
2055 ILMN_ .1731783 476 ATP1A1 -0.350 1.41E-04 0.292 1.21E-03
2056 ILMN_ .1731941 55937 APOM -0.288 9.34E-04 0.384 3.69E-05
2057 ILMN_ .1732127 64080 RBKS -1.516 2.28E-18 0.850 2.69E-12
2058 ILMN_ .1732187 55260 TMEM143 -0.784 1.21E-09 0.494 5.72E-06
2059 ILMN_ .1732291 653125 LOC653125 -0.518 2.38E-06 0.461 1.49E-05
2060 ILMN_ .1732375 60678 EEFSEC -0.317 1.48E-03 0.270 5.37E-03
2061 ILMN_ .1732555 9331 B4GALT6 -0.535 7.00E-07 0.302 7.74E-04
2062 ILMN_ .1733110 8045 RASSF7 -1.466 7.47E-19 0.337 4.32E-05
2063 ILMN_ .1733155 28964 GIT1 -0.320 9.70E-05 0.318 1.62E-04
2064 ILMN_ .1733615 22823 MTF2 -0.228 8.04E-03 0.405 1.57E-05
2065 ILMN_ .1733666 26258 PLDN -0.554 2.30E-07 0.250 3.97E-03
2066 ILMN_ .1733831 79605 PGBD5 -0.618 1.39E-08 1.060 1.01E-13
2067 ILMN_ .1733956 3376 IARS -0.332 5.40E-04 0.586 2.26E-07 2068 ILMN_ .1733998 10170 DHRS9 -0.863 1.76E-11 0.412 1.95E-05
2069 ILMN_ .1734096 9937 DCLRE1A -0.312 3.65E-04 0.477 8.77E-07
2070 ILMN_ .1734205 11186 RASSF1 -0.843 4.72E-11 0.509 1.12E-06
2071 ILMN_ 1734476 3796 KIF2A -0.396 1.18E-05 0.222 6.66E-03
2072 ILMN_ .1734696 2483 FRG1 -0.296 7.91E-04 0.608 5.43E-09
2073 ILMN_ .1734707 166012 CHST13 -0.953 5.22E-13 0.733 2.36E-10
2074 ILMN_ .1735075 267002 PGBD2 -1.039 1.37E-12 0.634 4.95E-08
2075 ILMN_ .1735093 8914 TIMELESS -0.801 1.18E-10 0.722 1.43E-09
2076 ILMN_ .1735499 131566 DCBLD2 -0.503 2.10E-07 0.779 4.78E-11
2077 ILMN_ .1735658 25914 RTTN -0.585 3.53E-06 0.781 2.02E-08
2078 ILMN_ .1736242 25894 PLEKHG4 -0.846 2.23E-12 0.437 1.88E-06
2079 ILMN_ .1736441 57026 PDXP -0.622 7.18E-09 0.470 1.69E-06
2080 ILMN_ .1736460 56890 MDM1 -0.592 3.04E-08 0.439 5.73E-06
2081 ILMN_ .1736546 151473 SLC16A14 -0.436 3.28E-06 0.309 2.86E-04
2082 ILMN_ .1736575 10155 TRIM28 -0.705 4.01E-10 0.321 2.51E-04
2083 ILMN_ .1736816 221150 C13orf3 -1.046 5.52E-13 0.780 1.13E-10
2084 ILMN_ .1736911 7111 TMOD1 -1.680 3.68E-18 1.068 1.62E-13
2085 ILMN_ .1736982 221692 PHACTR1 -0.407 1.50E-05 0.382 4.88E-05
2086 ILMN_ .1737195 64105 CENPK -0.921 7.86E-13 0.456 1.61E-06
2087 ILMN_ .1737205 4173 MCM4 -1.152 9.77E-14 0.540 1.56E-07
2088 ILMN_ .1737413 4436 MSH2 -0.626 1.19E-06 0.470 5.42E-05
2089 ILMN_ .1737604 55277 FLJ 10986 -0.563 4.39E-08 0.266 1.57E-03
2090 ILMN_ .1737611 6843 VAMP1 -0.562 3.14E-06 0.269 7.04E-03
2091 ILMN_ .1737663 129790 C7orfl3 -0.285 3.24E-03 0.244 5.02E-03
2092 ILMN_ .1737715 116039 OSR2 -0.507 2.93E-05 0.309 3.09E-03
2093 ILMN_ .1738027 672 BRCA1 -0.996 3.18E-13 0.425 5.31E-06
2094 ILMN_ .1738095 8864 PER2 -0.234 5.88E-03 0.275 1.82E-03
2095 ILMN_ .1738346 221154 EFHAl -0.218 3.80E-03 0.457 6.61E-07
2096 ILMN_ 1738449 57620 STIM2 -0.311 3.35E-04 0.245 3.46E-03
2097 ILMN_ .1738657 23314 SATB2 -0.661 6.69E-10 0.511 1.68E-07
2098 ILMN_ .1738784 5525 PPP2R5A -0.549 6.93E-07 0.299 1.94E-03
2099 ILMN_ .1739210 25936 NSL1 -0.282 6.49E-04 0.577 2.34E-08
2100 ILMN_ .1739253 10617 STAMBP -0.301 9.78E-04 0.473 3.27E-06
2101 ILMN_ .1739274 5162 PDHB -0.260 1.06E-03 0.236 2.29E-03
2102 ILMN_ .1739397 11146 GLMN -0.489 1.76E-06 0.242 5.84E-03
2103 ILMN_ .1739594 26027 ACOT11 -1.314 7.38E-16 0.258 2.95E-03
2104 ILMN_ .1739946 79001 VKORC1 -0.558 7.28E-08 0.269 2.00E-03
2105 ILMN_ .1740160 5335 PLCG1 -0.437 7.21E-07 0.443 8.15E-07
2106 ILMN_ .1740169 7301 TYR03 -1.007 3.31E-13 0.817 4.74E-11
2107 ILMN_ .1740265 11332 ACOT7 -1.182 1.93E-15 0.395 1.43E-05
2108 ILMN_ .1740291 10721 POLQ -0.986 1.74E-11 0.455 2.60E-05
2109 ILMN_ .1740413 158880 USP51 -0.295 1.44E-03 0.274 2.77E-03
2110 ILMN_ 1740490 284406 ZFP82 -0.235 8.81E-03 0.315 2.82E-04
2111 ILMN_ .1740512 286527 MGC39900 -1.041 3.98E-14 0.459 1.21E-06 2112 ILMN_ 1740604 26056 RAB11FIP5 -0.607 6.34E-09 0.278 1.02E-03
2113 ILMN_ .1740606 219790 RTKN2 -0.391 9.87E-04 0.299 8.81E-03
2114 ILMN_ .1741204 23588 KLHDC2 -0.667 1.14E-09 0.332 1.32E-04
2115 ILMN_ .1741224 283554 GPR137C -0.574 2.67E-05 0.746 2.08E-10
2116 ILMN_ .1741264 51650 MRPS33 -0.313 1.53E-04 0.595 8.86E-09
2117 ILMN_ .1741391 253959 RALGAPA1 -0.309 2.62E-04 0.663 1.92E-09
2118 ILMN_ 1741440 10559 SLC35A1 -0.447 5.93E-07 0.490 2.13E-07
2119 ILMN_ .1741459 8558 CDK10 -0.766 2.37E-08 0.388 5.07E-04
2120 ILMN_ .1741506 149134 LOCI 49134 -0.298 3.13E-03 0.387 2.61E-04
2121 ILMN_ .1741780 285193 DUSP28 -0.513 3.63E-08 0.489 1.52E-07
2122 ILMN_ .1741801 8317 CDC7 -1.268 1.47E-15 0.789 4.31E-11
2123 ILMN_ .1742145 9700 ESPL1 -1.371 4.46E-16 0.336 3.01E-04
2124 ILMN_ .1742382 9783 RIMS 3 -1.024 3.06E-14 0.480 4.82E-07
2125 ILMN_ .1742461 6675 UAP1 -0.357 4.03E-04 0.336 6.81E-04
2126 ILMN_ .1742534 1287 COL4A5 -1.032 1.14E-12 0.251 6.15E-03
2127 ILMN_ .1742541 9849 ZNF518A -0.212 9.97E-03 0.517 2.28E-07
2128 ILMN_ .1742922 5558 PRIM2A -0.413 5.67E-06 0.295 5.54E-04
2129 ILMN_ .1742935 7582 ZNF33B -0.887 1.60E-11 0.271 2.46E-03
2130 ILMN_ .1743104 83759 RBM4B -0.636 1.55E-10 0.633 3.79E-10
2131 ILMN_ .1743130 5738 PTGFRN -0.681 5.06E-10 0.481 6.39E-07
2132 ILMN_ .1743205 10347 ABCA7 -1.105 3.30E-12 0.370 1.34E-04
2133 ILMN_ .1743643 79364 ZXDC -0.397 6.20E-04 0.441 2.49E-05
2134 ILMN_ .1743711 650215 LOC650215 -0.328 8.39E-04 0.612 1.61E-07
2135 ILMN_ 1743747 23623 RUSC1 -0.527 1.30E-07 0.966 1.87E-13
2136 ILMN_ .1743770 9016 SLC25A14 -0.382 2.35E-04 0.580 5.23E-07
2137 ILMN_ .1743836 439921 MXRA7 -0.322 2.56E-04 0.277 7.71E-04
2138 ILMN_ .1743911 51629 SLC25A39 -0.427 1.29E-06 0.288 4.02E-04
2139 ILMN_ 1744347 127295 LOCI 27295 -0.308 4.20E-04 0.303 6.53E-04
2140 ILMN_ .1744725 90135 BTBD6 -0.591 2.59E-09 0.409 2.65E-06
2141 ILMN_ 1744795 6907 TBL1X -0.236 8.64E-03 0.398 6.16E-05
2142 ILMN_ .1745130 23543 RBM9 -0.453 4.22E-06 0.376 6.54E-05
2143 ILMN_ .1745172 3608 ILF2 -0.519 8.25E-08 0.247 1.70E-03
2144 ILMN_ .1745223 23580 CDC42EP4 -0.537 2.39E-07 1.054 9.65E-14
2145 ILMN_ .1745282 5891 RAGE -0.308 7.83E-04 0.742 3.40E-10
2146 ILMN_ .1745573 79573 TTC13 -0.493 7.93E-07 0.288 1.07E-03
2147 ILMN_ 1745764 83850 FAM62C -0.294 9.63E-03 0.460 1.60E-04
2148 ILMN_ .1745772 10973 ASCC3 -0.328 9.89E-04 0.314 9.15E-04
2149 ILMN_ .1745813 26128 KIAA1279 -0.489 5.40E-08 0.294 1.97E-04
2150 ILMN_ .1745826 83473 KATNAL2 -0.630 1.72E-08 0.471 3.08E-06
2151 ILMN_ .1745887 23014 FBX021 -0.236 8.99E-03 0.466 2.83E-06
2152 ILMN_ .1746206 22994 AZI1 -1.098 3.90E-13 0.779 5.58E-10
2153 ILMN_ .1746252 391811 LOC391811 -0.844 1.44E-11 0.421 7.51E-06
2154 ILMN_ .1746492 11020 RABL4 -0.487 1.86E-06 0.279 2.26E-03
2155 ILMN_ _1746784 122060 SLAIN 1 -1.039 3.58E-12 0.426 5.60E-05 2156 ILMN_ .1746819 727 C5 -1.546 6.24E-18 0.842 1.86E-11
2157 ILMN_ .1746917 729843 LOC729843 -0.490 1.79E-07 0.611 3.35E-09
2158 ILMN_ .1747016 55165 CEP55 -0.930 3.95E-13 0.300 3.40E-04
2159 ILMN_ .1747067 4861 NPAS1 -0.517 2.21E-06 0.574 2.40E-07
2160 ILMN_ .1747078 219844 HYLS1 -0.930 6.47E-12 0.535 5.00E-07
2161 ILMN_ .1747183 283464 GXYLT1 -0.644 1.39E-07 0.450 2.50E-05
2162 ILMN_ 1747504 25909 AHCTF1 -0.327 4.04E-04 0.466 1.71E-06
2163 ILMN_ .1747577 210 ALAD -1.009 5.41E-13 0.383 6.26E-05
2164 ILMN_ .1747824 7639 ZNF85 -0.351 9.97E-04 0.498 1.03E-05
2165 ILMN_ .1748093 5050 PAFAH1B3 -1.590 1.10E-18 0.564 4.48E-08
2166 ILMN_ .1748352 1515 CTSL2 -1.380 3.15E-17 1.028 4.64E-14
2167 ILMN_ .1748591 4953 ODC1 -1.210 7.83E-16 0.300 4.06E-04
2168 ILMN_ .1748650 84311 MRPL45 -0.436 6.80E-07 0.219 4.43E-03
2169 ILMN_ .1748827 388564 LOC388564 -0.637 3.14E-08 0.274 2.60E-03
2170 ILMN_ .1748883 1032 CDKN2D -0.899 8.56E-12 0.962 2.38E-12
2171 ILMN_ .1748908 11212 PROSC -0.196 9.73E-03 0.300 2.73E-04
2172 ILMN_ .1748926 84928 TMEM209 -0.280 2.19E-03 0.426 9.00E-06
2173 ILMN_ 1749410 8502 PKP4 -1.419 5.38E-16 0.639 4.26E-09
2174 ILMN_ .1749799 79366 NSBP1 -0.495 1.40E-06 0.297 1.02E-03
2175 ILMN_ 1749834 388588 LOC388588 -0.921 5.28E-12 0.364 9.24E-05
2176 ILMN_ .1749838 7593 MZF1 -0.477 2.00E-05 0.385 2.71E-04
2177 ILMN_ .1749875 728715 LOC728715 -1.167 l.lOE-11 0.751 3.72E-08
2178 ILMN_ .1750102 146956 EME1 -0.982 7.28E-11 0.529 6.92E-06
2179 ILMN_ .1750785 84958 SYTL1 -0.716 5.47E-08 0.748 3.53E-09
2180 ILMN_ .1750800 48 ACOl -1.620 2.52E-19 0.398 6.82E-06
2181 ILMN_ .1751072 58477 SRPRB -0.244 2.43E-03 0.280 8.50E-04
2182 ILMN_ 1751444 64151 NCAPG -1.184 2.55E-15 0.408 1.25E-05
2183 ILMN_ .1751692 7565 ZNF17 -0.214 3.04E-03 0.203 6.18E-03
2184 ILMN_ .1751726 649049 LOC649049 -0.654 8.52E-10 0.285 5.37E-04
2185 ILMN_ .1751753 3418 IDH2 -0.657 4.68E-08 0.616 1.66E-07
2186 ILMN_ .1751773 10714 POLD3 -0.580 1.49E-08 0.352 6.74E-05
2187 ILMN_ .1751785 10655 DMRT2 -0.988 1.63E-13 0.714 1.81E-10
2188 ILMN_ .1751963 55063 ZCWPW1 -0.243 4.96E-03 0.737 8.12E-10
2189 ILMN_ .1752249 9780 FAM38A -0.725 4.44E-10 0.269 1.49E-03
2190 ILMN_ .1752394 57820 CCNB1IP1 -0.382 2.99E-05 0.544 1.32E-07
2191 ILMN_ .1752631 8545 CGGBP1 -0.213 7.19E-03 0.843 2.87E-12
2192 ILMN_ .1752728 2517 FUCA1 -0.249 5.13E-03 0.348 2.29E-04
2193 ILMN_ .1752953 83596 BCL2L12 -0.628 1.18E-09 0.223 4.52E-03
2194 ILMN_ .1753063 56992 KIF15 -1.434 3.23E-17 0.580 4.69E-09
2195 ILMN_ .1753279 10949 HNRNPAO -0.874 2.64E-12 0.464 1.05E-06
2196 ILMN_ .1753353 7884 SLBP -0.667 5.58E-10 0.317 9.53E-05
2197 ILMN_ .1753370 25841 ABTB2 -0.237 6.08E-03 0.666 6.14E-09
2198 ILMN_ .1753534 6222 RPS18 -0.206 4.89E-03 0.244 1.36E-03
2199 ILMN_ .1753582 6118 RPA2 -0.525 2.29E-08 0.493 9.00E-08 2200 ILMN_ .1753613 3202 HOXA5 -0.698 1.23E-09 0.875 1.32E-11
2201 ILMN_ .1753719 2958 GTF2A2 -0.463 6.95E-07 0.255 1.94E-03
2202 ILMN_ .1753782 10781 ZNF266 -0.332 1.82E-04 0.407 7.79E-06
2203 ILMN_ .1753980 731950 LOC731950 -0.261 4.98E-03 0.727 4.55E-09
2204 ILMN_ .1754114 90024 FLJ20021 -0.291 5.55E-03 0.925 1.45E-11
2205 ILMN_ .1754179 8906 AP1G2 -0.752 2.79E-10 0.723 8.51E-10
2206 ILMN_ .1754234 10771 ZMYND11 -1.165 1.30E-15 0.356 3.16E-05
2207 ILMN_ .1754272 64785 GINS 3 -0.543 6.27E-08 0.630 4.18E-09
2208 ILMN_ 1754400 386608 AYPlpl -0.287 1.07E-03 0.497 7.06E-07
2209 ILMN_ 1754489 84961 FBXL20 -0.302 1.27E-04 0.447 4.86E-07
2210 ILMN_ .1754727 114928 GPRASP2 -0.484 2.57E-07 0.421 3.76E-06
2211 ILMN_ .1754858 23178 PASK -0.869 3.50E-11 0.372 1.13E-04
2212 ILMN_ .1754865 400455 LOC400455 -0.491 1.43E-07 0.283 5.25E-04
2213 ILMN_ .1754880 400322 HERC2P2 -0.256 1.24E-02 0.388 2.99E-04
2214 ILMN_ 1754894 128346 Clorfl62 -0.354 1.72E-05 0.579 6.76E-09
2215 ILMN_ .1754912 2733 GLE1 -0.575 1.97E-09 0.654 2.61E-10
2216 ILMN_ .1755383 55227 LRRC1 -0.303 1.80E-03 0.638 1.09E-08
2217 ILMN_ .1755391 23568 ARL2BP -0.385 8.58E-06 0.463 5.52E-07
2218 ILMN_ .1755741 1602 DACH1 -0.965 3.62E-12 0.607 5.14E-08
2219 ILMN_ .1755909 54994 C20orfl l -0.839 9.45E-12 0.253 1.87E-03
2220 ILMN_ .1756049 51559 NT5DC3 -1.159 1.95E-15 0.431 3.22E-06
2221 ILMN_ .1756071 4240 MFGE8 -0.273 1.51E-03 0.767 1.50E-10
2222 ILMN_ .1756162 11340 EXOSC8 -0.705 2.91E-06 0.545 2.99E-05
2223 ILMN_ .1756445 11243 PMF1 -0.399 2.67E-04 0.462 1.77E-05
2224 ILMN_ .1756469 2593 GAMT -1.378 1.50E-16 0.679 1.60E-09
2225 ILMN_ .1756541 10608 MXD4 -1.552 6.74E-16 1.103 6.46E-13
2226 ILMN_ .1756550 54830 NUP62CL -0.443 1.12E-05 0.731 1.88E-09
2227 ILMN_ .1756590 90196 SYS1 -0.218 1.06E-02 0.431 1.04E-05
2228 ILMN_ .1756685 64798 DEPDC6 -2.004 2.64E-19 0.508 2.96E-06
2229 ILMN_ .1756705 63922 CHTF18 -1.389 3.82E-15 0.451 2.33E-05
2230 ILMN_ .1756878 55334 SLC39A9 -0.240 5.57E-03 0.231 8.84E-03
2231 ILMN_ .1756898 57017 COQ9 -0.363 3.72E-05 0.276 1.06E-03
2232 ILMN_ .1756920 8751 ADAM 15 -1.233 1.98E-15 0.726 6.45E-10
2233 ILMN_ .1757230 58500 ZNF250 -0.536 1.48E-07 0.463 1.94E-06
2234 ILMN_ .1757343 8761 PABPC4 -0.200 9.48E-03 0.241 2.93E-03
2235 ILMN_ .1757521 1158 CKM -0.380 9.12E-05 0.283 1.18E-03
2236 ILMN_ .1757636 133383 C5orf35 -0.592 4.18E-08 0.516 7.03E-07
2237 ILMN_ .1757697 55247 NEIL3 -1.295 6.73E-15 1.218 3.21E-14
2238 ILMN_ .1757736 10265 IRX5 -1.610 1.44E-18 0.446 2.58E-06
2239 ILMN_ .1758173 147184 TMEM99 -0.533 1.05E-07 0.677 1.15E-09
2240 ILMN_ .1758311 10276 NET1 -0.625 8.53E-09 0.433 7.00E-06
2241 ILMN_ .1758337 7760 ZNF213 -0.277 5.20E-03 0.487 7.86E-06
2242 ILMN_ 1758474 8575 PRKRA -0.541 9.51E-08 0.526 1.99E-07
2243 ILMN_ .1758523 21 ABCA3 -0.851 5.90E-11 0.543 5.20E-07 2244 ILMN_ .1758629 29980 DONSON -0.590 6.58E-08 0.492 9.02E-07
2245 ILMN_ .1758672 83641 FAM107B -0.826 1.36E-10 0.486 1.18E-06
2246 ILMN_ .1758728 2189 FANCG -1.332 3.27E-16 0.896 2.29E-12
2247 ILMN_ .1758806 755 C21orf2 -0.409 1.86E-05 0.450 6.15E-06
2248 ILMN_ .1759030 11183 MAP4K5 -0.233 4.03E-03 0.337 1.31E-04
2249 ILMN_ .1759184 84798 C19orf48 -0.651 3.88E-09 0.774 1.56E-10
2250 ILMN_ .1759613 84968 PNMA6A -0.289 7.26E-04 0.265 1.62E-03
2251 ILMN_ .1759772 115399 LRRC56 -0.397 2.71E-05 0.250 4.61E-03
2252 ILMN_ .1759948 286140 RNF5P1 -0.524 1.47E-07 0.475 9.37E-07
2253 ILMN_ .1760102 162972 ZNF550 -0.339 2.21E-04 0.315 6.23E-04
2254 ILMN_ .1760174 56922 MCCC1 -0.271 2.92E-03 0.266 3.78E-03
2255 ILMN_ .1760201 1786 DNMT1 -0.366 2.68E-05 0.228 5.17E-03
2256 ILMN_ .1760245 131616 TMEM42 -0.275 1.32E-03 0.874 7.93E-12
2257 ILMN_ .1760360 26046 RNF160 -0.212 6.85E-03 0.297 3.07E-04
2258 ILMN_ .1760667 84265 POLR3GL -0.257 1.81E-03 0.419 7.63E-06
2259 ILMN_ .1760714 6188 RPS3 -0.448 7.20E-07 0.284 5.52E-04
2260 ILMN_ .1760792 55975 KLHL7 -0.296 2.18E-03 0.341 5.32E-04
2261 ILMN_ .1760954 8562 DENR -0.274 8.67E-04 0.330 9.06E-05
2262 ILMN_ .1761010 5096 PCCB -0.604 6.50E-10 0.446 4.73E-07
2263 ILMN_ .1761131 10455 PECI -0.557 2.66E-07 0.460 7.50E-06
2264 ILMN_ .1761138 286257 C9orfl42 -0.677 1.37E-09 0.275 1.47E-03
2265 ILMN_ .1761309 203054 ADCK5 -0.368 6.68E-05 0.359 8.45E-05
2266 ILMN_ .1761560 148479 PHF13 -0.302 3.14E-04 0.213 6.89E-03
2267 ILMN_ .1762327 79758 DHRS12 -0.392 1.14E-04 0.310 1.17E-03
2268 ILMN_ .1762407 81928 CABLES2 -0.895 8.43E-12 0.606 2.91E-08
2269 ILMN_ .1762426 200895 DHFRL1 -0.357 1.35E-04 0.430 1.15E-05
2270 ILMN_ .1762526 27127 SMC IB -0.462 9.35E-06 0.891 3.44E-12
2271 ILMN_ .1762606 282679 AQP11 -0.313 6.26E-04 0.519 7.68E-07
2272 ILMN_ .1762712 3087 HHEX -0.279 1.18E-03 0.304 5.86E-04
2273 ILMN_ .1762713 199675 C19orf59 -0.487 2.65E-07 0.405 8.09E-06
2274 ILMN_ .1762747 6138 RPL15 -0.610 2.85E-08 0.357 1.35E-04
2275 ILMN_ .1763127 1238 CCBP2 -1.154 1.50E-11 0.387 4.28E-04
2276 ILMN_ .1763208 7556 ZNF10 -0.415 5.39E-05 0.568 5.28E-07
2277 ILMN_ .1763568 84287 ZDHHC16 -0.321 1.66E-04 0.425 4.51E-06
2278 ILMN_ .1763852 32 ACACB -1.249 3.08E-15 1.067 1.62E-13
2279 ILMN_ .1764188 203238 C9orf93 -0.435 1.75E-06 0.437 1.72E-06
2280 ILMN_ .1764522 64327 LMBR1 -0.455 7.62E-07 0.418 4.75E-06
2281 ILMN_ .1764596 4357 MPST -0.837 1.93E-10 0.463 9.45E-06
2282 ILMN_ .1764729 3714 JAG2 -0.849 8.77E-12 0.491 7.38E-07
2283 ILMN_ .1764813 145173 B3GALTL -0.379 3.46E-05 0.438 5.94E-06
2284 ILMN_ .1765076 55198 APPL2 -0.507 1.17E-05 0.461 8.43E-06
2285 ILMN_ .1765532 7936 RDBP -0.256 1.82E-03 0.216 8.09E-03
2286 ILMN_ .1766125 9361 LONP1 -0.246 1.56E-03 0.368 2.34E-05
2287 ILMN_ .1766309 129138 ANKRD54 -0.727 1.03E-09 0.229 6.98E-03 2288 ILMN_ .1766363 2322 FLT3 -0.773 2.45E-10 0.554 2.17E-07
2289 ILMN_ .1766366 130026 ICAIL -0.238 7.68E-03 0.267 2.71E-03
2290 ILMN_ .1766918 8645 KCNK5 -0.921 1.41E-11 0.269 3.99E-03
2291 ILMN_ .1767260 165055 CCDC138 -0.877 1.43E-11 0.426 7.62E-06
2292 ILMN_ .1767337 94097 SFXN5 -0.316 1.05E-03 0.565 4.26E-07
2293 ILMN_ .1767365 5058 PAK1 -0.432 2.61E-06 0.772 6.19E-11
2294 ILMN_ .1767481 91419 XRCC6BP1 -2.093 4.34E-19 0.570 1.30E-06
2295 ILMN_ .1767523 55540 IL17RB -0.235 5.59E-03 0.313 4.77E-04
2296 ILMN_ .1767542 56906 THAP10 -0.295 1.15E-03 1.199 7.86E-15
2297 ILMN_ .1767642 120534 Cl lorf46 -0.428 5.67E-06 0.343 1.08E-04
2298 ILMN_ .1768004 27250 PDCD4 -1.295 4.19E-15 0.362 1.27E-04
2299 ILMN_ .1768050 60592 SCOC -0.310 2.31E-03 0.487 3.92E-06
2300 ILMN_ .1768110 51776 ZAK -1.365 7.95E-17 0.568 4.87E-08
2301 ILMN_ .1768202 170961 ANKRD24 -0.423 8.46E-05 0.507 4.22E-07
2302 ILMN_ .1768271 60682 SMAP1 -0.446 1.82E-06 0.284 8.48E-04
2303 ILMN_ .1768284 286530 P2RY8 -0.554 1.16E-07 0.415 8.21E-06
2304 ILMN_ .1768311 728888 LOC728888 -0.564 2.49E-07 0.699 2.82E-09
2305 ILMN_ 1768449 5635 PRPSAP1 -0.562 8.72E-08 0.986 4.57E-13
2306 ILMN_ .1768575 6441 SFTPD -1.210 3.49E-14 0.680 1.38E-08
2307 ILMN_ .1768816 7112 TMPO -0.521 7.36E-08 0.424 3.31E-06
2308 ILMN_ .1768867 8546 AP3B1 -0.857 1.77E-12 0.227 4.61E-03
2309 ILMN_ .1769031 2475 FRAPl -0.323 1.77E-03 0.319 1.85E-03
2310 ILMN_ .1769390 116236 ABHD15 -1.217 3.05E-14 0.395 7.43E-05
2311 ILMN_ .1769409 90871 C9orfl23 -0.291 2.85E-04 0.218 5.46E-03
2312 ILMN_ .1769451 10994 ILVBL -0.734 8.81E-11 0.437 2.90E-06
2313 ILMN_ .1769473 29072 SETD2 -0.334 8.89E-05 0.453 1.60E-06
2314 ILMN_ .1769508 54965 PIGX -0.359 2.93E-04 0.317 1.25E-03
2315 ILMN_ .1769601 93627 MGC16169 -0.273 1.90E-03 0.518 7.21E-07
2316 ILMN_ .1769634 201254 STRA13 -1.134 5.92E-15 0.449 2.52E-06
2317 ILMN_ .1769720 27067 STAU2 -0.311 2.76E-03 0.326 1.49E-03
2318 ILMN_ .1769911 81539 SLC38A1 -1.176 4.84E-14 0.891 9.31E-12
2319 ILMN_ .1769926 1627 DBN1 -0.766 3.49E-10 0.863 2.83E-11
2320 ILMN_ .1770031 55347 ABHD10 -0.530 6.25E-07 0.281 2.36E-03
2321 ILMN_ .1770035 57727 NCOA5 -0.579 9.20E-09 0.232 3.51E-03
2322 ILMN_ .1770048 51611 DPH5 -0.332 3.07E-04 0.378 6.94E-05
2323 ILMN_ .1770053 5931 RBBP7 -0.936 8.50E-13 0.251 2.92E-03
2324 ILMN_ .1770172 79862 ZNF669 -0.586 8.42E-07 0.704 2.00E-09
2325 ILMN_ .1770244 10951 CBX1 -0.547 6.17E-07 0.270 3.96E-03
2326 ILMN_ .1770498 728411 LOC728411 -0.901 2.26E-10 0.278 3.50E-03
2327 ILMN_ .1770505 638 BIK -1.902 1.76E-21 0.699 1.48E-10
2328 ILMN_ .1770641 26249 KLHL3 -0.505 9.70E-07 1.017 1.44E-13
2329 ILMN_ .1770678 84733 CBX2 -0.606 4.37E-09 0.594 8.20E-09
2330 ILMN_ .1770732 8533 COPS3 -0.876 3.20E-11 0.459 8.07E-06
2331 ILMN_ .1770765 124221 MGC52282 -0.277 3.13E-03 0.243 8.02E-03 2332 ILMN_ .1770787 23564 DDAH2 -0.410 8.62E-05 0.556 6.49E-07
2333 ILMN_ .1770850 9240 PNMA1 -0.346 1.08E-03 0.321 2.12E-03
2334 ILMN_ .1770936 84274 COQ5 -0.309 3.26E-04 0.560 5.27E-08
2335 ILMN_ .1771003 54930 HAUS4 -0.391 7.91E-06 0.614 4.65E-09
2336 ILMN_ .1771224 220134 SKA1 -0.523 1.57E-05 0.623 6.69E-07
2337 ILMN_ .1771411 29929 ALG6 -0.804 2.50E-11 0.339 1.28E-04
2338 ILMN_ .1771593 6240 RRM1 -0.832 3.83E-12 0.566 1.00E-08
2339 ILMN_ .1771964 2941 GSTA4 -0.523 2.00E-06 0.810 1.37E-11
2340 ILMN_ .1772207 653377 LOC653377 -0.767 1.88E-10 0.238 3.61E-03
2341 ILMN_ .1772446 84915 C12orf34 -0.504 4.91E-06 1.213 2.34E-14
2342 ILMN_ .1772700 129787 TMEM18 -0.417 3.20E-06 0.399 9.88E-06
2343 ILMN_ .1772731 3029 HAGH -0.266 5.74E-04 0.610 1.92E-09
2344 ILMN_ .1772743 10026 PIGK -0.786 1.02E-09 0.719 3.66E-09
2345 ILMN_ .1772796 140735 DYNLL2 -0.388 9.30E-05 0.351 1.56E-04
2346 ILMN_ .1772798 10776 ARPP19 -0.845 1.09E-11 0.236 5.19E-03
2347 ILMN_ .1772910 2619 GAS1 -0.923 8.14E-12 0.253 4.70E-03
2348 ILMN_ .1773002 730417 LOC730417 -1.194 5.91E-15 0.489 1.45E-06
2349 ILMN_ .1773073 5264 PHYH -0.633 2.22E-08 0.748 1.82E-10
2350 ILMN_ .1773369 51642 MRPL48 -0.623 2.98E-08 0.315 7.72E-04
2351 ILMN_ .1773395 5959 RDH5 -0.323 2.88E-03 0.378 7.26E-04
2352 ILMN_ .1773576 8895 CPNE3 -0.440 6.40E-06 0.576 9.71E-08
2353 ILMN_ .1773645 29925 GMPPB -0.364 7.95E-04 0.590 1.80E-07
2354 ILMN_ .1773780 65990 FAM173A -0.415 4.91E-06 0.301 4.44E-04
2355 ILMN_ .1773809 116113 FOXP4 -0.323 4.16E-04 0.306 6.19E-04
2356 ILMN_ .1773885 55929 DMAP1 -0.369 1.30E-05 0.221 4.78E-03
2357 ILMN_ .1774062 292 SLC25A5 -0.250 1.17E-03 0.282 4.60E-04
2358 ILMN_ 1774547 23164 MPRIP -0.674 3.05E-09 0.409 1.19E-05
2359 ILMN_ .1774589 55721 IQCC -0.791 4.93E-11 0.528 9.74E-08
2360 ILMN_ .1774596 26580 BSCL2 -0.642 1.14E-09 0.291 4.55E-04
2361 ILMN_ .1774930 8556 CDC14A -0.483 2.36E-06 0.264 2.00E-03
2362 ILMN_ .1775036 26984 SEC22A -0.276 1.65E-03 0.412 2.08E-05
2363 ILMN_ .1775224 4846 NOS3 -0.754 2.99E-09 0.456 4.13E-06
2364 ILMN_ .1775235 3899 AFF3 -0.851 1.17E-10 0.362 2.54E-04
2365 ILMN_ 1775448 5217 PFN2 -0.288 1.50E-03 0.552 1.78E-07
2366 ILMN_ .1775703 79090 TRAPPC6A -0.496 2.69E-07 0.841 5.50E-12
2367 ILMN_ .1775814 2690 GHR -0.401 6.96E-05 0.607 1.18E-07
2368 ILMN_ .1775829 64065 PERP -0.559 1.92E-06 0.473 1.49E-05
2369 ILMN_ .1776005 58505 OSTC -0.217 4.59E-03 0.365 1.74E-05
2370 ILMN_ .1776052 148915 LOCI 48915 -0.591 1.19E-08 0.350 7.63E-05
2371 ILMN_ .1776352 63915 MUTED -0.470 1.29E-06 0.310 4.77E-04
2372 ILMN_ .1776375 5300 PIN1 -0.639 3.99E-10 0.318 9.14E-05
2373 ILMN_ .1776490 78995 C17orf53 -0.650 2.41E-09 0.532 5.63E-08
2374 ILMN_ .1776515 65258 MPPE1 -0.594 5.94E-09 0.614 4.84E-09
2375 ILMN_ .1776516 3706 ITPKA -0.857 3.80E-12 1.482 6.40E-18 2376 ILMN_ .1776519 5909 RAP 1 GAP -0.243 8.79E-03 0.462 1.20E-06
2377 ILMN_ .1776577 79075 DSCC1 -1.196 1.42E-13 0.832 2.83E-10
2378 ILMN_ .1776674 29901 SAC3D1 -1.281 1.11E-15 0.415 1.11E-05
2379 ILMN_ .1776724 130574 LYPD6 -0.398 2.67E-03 0.422 1.00E-04
2380 ILMN_ .1776993 22796 COG2 -0.378 4.33E-05 0.398 2.21E-05
2381 ILMN_ .1777096 6996 TDG -0.222 3.82E-03 0.292 3.94E-04
2382 ILMN_ .1777190 1675 CFD -0.631 4.68E-10 0.493 1.23E-07
2383 ILMN_ .1777233 1870 E2F2 -1.413 2.63E-16 1.713 1.27E-18
2384 ILMN_ 1777344 6207 RPS13 -0.359 2.06E-05 0.237 2.32E-03
2385 ILMN_ .1777378 170622 COMMD6 -0.692 3.55E-10 0.504 2.67E-07
2386 ILMN_ .1777564 4085 MAD2L1 -1.026 3.31E-12 0.326 4.31E-04
2387 ILMN_ .1777740 51337 C8orf55 -0.810 9.96E-11 0.667 4.88E-09
2388 ILMN_ .1777745 257415 FAM133B -0.548 1.77E-07 0.748 2.64E-10
2389 ILMN_ .1778152 63979 FIGNL1 -0.837 3.15E-12 0.716 1.41E-10
2390 ILMN_ .1778173 50808 AK3 -0.837 5.76E-12 0.684 6.71E-10
2391 ILMN_ .1778240 54438 GFOD1 -0.340 8.84E-04 0.682 3.52E-08
2392 ILMN_ .1778347 318 NUDT2 -0.487 1.12E-07 0.417 2.90E-06
2393 ILMN_ .1778360 5834 PYGB -0.404 1.01E-05 0.531 1.77E-07
2394 ILMN_ .1778488 55255 WDR41 -0.431 2.27E-06 0.294 4.48E-04
2395 ILMN_ .1778557 8621 CDC2L5 -0.461 5.80E-07 0.237 3.34E-03
2396 ILMN_ .1778684 9577 BRE -0.584 3.03E-08 0.471 1.39E-06
2397 ILMN_ .1778890 122769 PPIL5 -0.600 6.81E-09 0.331 1.08E-04
2398 ILMN_ .1779014 7259 TSPYL1 -0.200 8.85E-03 0.244 2.30E-03
2399 ILMN_ .1779228 1000 CDH2 -1.266 7.64E-15 0.864 7.38E-11
2400 ILMN_ .1779256 84071 ARMC2 -0.255 2.30E-03 0.403 1.24E-05
2401 ILMN_ .1779423 63931 MRPS14 -0.432 1.03E-05 0.241 6.42E-03
2402 ILMN_ 1779448 80303 EFHDl -0.598 6.55E-08 0.640 3.41E-09
2403 ILMN_ .1779536 55857 NCRNA00153 -0.448 1.36E-05 0.628 4.96E-08
2404 ILMN_ .1779616 8802 SUCLG1 -0.450 2.82E-07 0.339 2.90E-05
2405 ILMN_ .1779711 51514 DTL -0.893 3.01E-10 0.794 9.59E-10
2406 ILMN_ .1779855 8630 HSD17B6 -0.322 1.61E-03 0.363 2.24E-04
2407 ILMN_ .1780132 57161 PELI2 -0.594 7.63E-09 0.680 5.63E-10
2408 ILMN_ .1780141 51669 TMEM66 -0.287 4.94E-04 0.633 3.69E-09
2409 ILMN_ .1780236 5372 PMM1 -1.074 1.22E-14 0.612 6.38E-09
2410 ILMN_ .1780283 198437 C20orf201 -0.438 3.00E-04 0.331 3.81E-03
2411 ILMN_ .1780397 80342 TRAF3IP3 -0.375 5.53E-05 0.280 1.65E-03
2412 ILMN_ .1780698 84936 ZFYVE19 -0.296 1.11E-03 0.435 5.83E-06
2413 ILMN_ .1780773 400027 LOC400027 -0.348 1.48E-04 0.573 8.95E-08
2414 ILMN_ .1781419 51501 Cl lorf73 -0.256 2.30E-03 0.354 7.51E-05
2415 ILMN_ .1781454 8480 RAE1 -0.310 1.57E-04 0.223 4.81E-03
2416 ILMN_ .1781906 84991 RBM17 -0.457 1.21E-06 0.352 5.98E-05
2417 ILMN_ .1782004 579 BAPX1 -0.691 4.89E-11 0.836 1.12E-12
2418 ILMN_ .1782079 124961 ZFP3 -0.342 6.81E-04 0.292 3.18E-03
2419 ILMN_ .1782439 1266 CNN3 -0.567 7.89E-08 1.161 1.65E-14 2420 ILMN_ .1782609 10735 STAG2 -0.232 6.39E-03 0.306 7.20E-04
2421 ILMN_ .1782688 79896 THNSL1 -0.637 8.99E-08 0.426 5.38E-05
2422 ILMN_ .1782730 25888 ZNF473 -0.512 1.21E-06 0.353 3.65E-05
2423 ILMN_ .1782745 5933 RBL1 -0.766 5.49E-10 0.320 5.70E-04
2424 ILMN_ .1782813 1719 DHFR -0.389 7.97E-05 0.313 1.03E-03
2425 ILMN_ .1783075 253714 C6orfl67 -0.628 9.49E-09 0.629 1.22E-08
2426 ILMN_ .1783333 56942 C16orf61 -0.209 7.47E-03 0.530 1.04E-07
2427 ILMN_ .1783337 26063 DECR2 -0.671 1.96E-08 0.403 7.54E-05
2428 ILMN_ .1783610 3070 HELLS -0.571 6.01E-08 0.855 1.03E-11
2429 ILMN_ .1783676 80071 CCDC15 -1.360 4.73E-16 0.974 1.66E-12
2430 ILMN_ .1783684 648695 LOC648695 -0.637 1.65E-08 0.300 8.04E-04
2431 ILMN_ .1783753 51060 TXNDC12 -1.740 1.37E-19 0.490 6.17E-07
2432 ILMN_ .1783798 2622 GAS 8 -0.593 2.60E-07 0.381 1.87E-04
2433 ILMN_ .1783805 29944 PNMA3 -0.586 6.33E-08 0.305 7.34E-04
2434 ILMN_ .1783985 51004 COQ6 -0.762 1.44E-10 0.671 2.07E-09
2435 ILMN_ .1783996 64789 DEMI -0.689 4.57E-10 0.869 1.01E-12
2436 ILMN_ 1784040 9476 NAPSA -0.257 2.11E-03 0.649 2.33E-09
2437 ILMN_ .1784287 7049 TGFBR3 -0.643 6.88E-10 1.380 1.14E-17
2438 ILMN_ .1784292 57037 ANKMY2 -0.375 7.66E-05 0.297 1.01E-03
2439 ILMN_ .1784300 7277 TUBA4A -1.856 1.33E-18 0.963 1.75E-12
2440 ILMN_ 1784467 23225 NUP210 -1.424 1.30E-16 0.324 4.48E-04
2441 ILMN_ .1784860 5983 RFC3 -0.884 1.84E-10 0.363 4.86E-04
2442 ILMN_ .1784880 51616 TAF9L -0.813 7.71E-11 0.608 3.29E-08
2443 ILMN_ .1785010 93492 TPTE2 -0.303 3.99E-03 0.593 9.59E-07
2444 ILMN_ .1785095 155066 ATP6V0E2 -0.360 2.20E-04 0.849 6.04E-11
2445 ILMN_ .1785113 4594 MUT -0.285 1.96E-03 0.514 1.27E-06
2446 ILMN_ .1785191 28978 TMEM14A -0.426 6.60E-06 0.282 9.94E-04
2447 ILMN_ .1785198 54107 POLE3 -0.795 2.23E-11 0.234 3.89E-03
2448 ILMN_ .1785284 4329 ALDH6A1 -0.762 1.17E-09 0.331 6.10E-04
2449 ILMN_ .1785387 114625 ERMAP -0.409 1.11E-03 0.270 6.30E-03
2450 ILMN_ .1785756 731314 LOC731314 -1.283 3.40E-15 0.525 6.07E-07
2451 ILMN_ .1785914 990 CDC6 -0.263 8.93E-03 0.479 1.43E-05
2452 ILMN_ .1786015 10664 CTCF -0.687 1.28E-09 0.285 8.55E-04
2453 ILMN_ .1786016 9557 CHD1L -0.770 3.75E-11 0.293 5.66E-04
2454 ILMN_ .1786065 29128 UHRF1 -1.240 4.63E-16 0.298 4.71E-04
2455 ILMN_ .1786326 79047 KCTD15 -0.435 7.98E-05 0.727 2.55E-08
2456 ILMN_ .1786665 162655 ZNF519 -0.420 6.18E-05 0.424 6.67E-05
2457 ILMN_ .1786759 746 Cl lorflO -0.264 1.29E-03 0.433 3.57E-06
2458 ILMN_ .1786852 85364 ZCCHC3 -0.225 5.58E-03 0.256 1.95E-03
2459 ILMN_ .1786893 10181 RBM5 -0.198 1.05E-02 0.450 1.53E-06
2460 ILMN_ .1787248 10572 SIVA -1.288 7.26E-17 0.240 2.82E-03
2461 ILMN_ .1787251 23002 DA AMI -0.325 8.66E-04 1.015 1.88E-12
2462 ILMN_ .1787259 285498 RNF212 -0.442 2.90E-06 0.292 6.32E-04
2463 ILMN_ .1787280 79000 Clorfl35 -0.482 5.01E-06 0.592 1.13E-07 2464 ILMN_ .1787324 84080 C16orf48 -0.617 1.11E-08 0.577 4.12E-08
2465 ILMN_ .1787415 64089 SNX16 -0.260 9.14E-04 0.620 1.99E-09
2466 ILMN_ .1787539 7730 ZNF177 -0.305 4.22E-04 0.394 1.96E-05
2467 ILMN_ .1787691 163732 CITED4 -0.667 2.09E-09 0.441 3.11E-06
2468 ILMN_ .1787808 80254 CEP63 -0.755 1.06E-10 0.425 6.66E-06
2469 ILMN_ .1787843 84263 HSDL2 -0.505 2.77E-07 0.515 2.94E-07
2470 ILMN_ .1787923 57104 PNPLA2 -0.259 3.04E-03 0.262 3.03E-03
2471 ILMN_ .1788099 25804 LSM4 -0.896 5.41E-11 0.524 2.16E-06
2472 ILMN_ .1788149 79858 NEK11 -0.302 1.51E-03 0.283 1.17E-03
2473 ILMN_ .1788363 4292 MLH1 -0.512 3.31E-07 0.510 2.91E-07
2474 ILMN_ .1788384 23731 C9orf5 -0.524 3.10E-07 0.311 5.96E-04
2475 ILMN_ .1788387 55757 UGCGL2 -0.270 6.86E-03 0.283 4.54E-03
2476 ILMN_ .1788468 55082 ARGLU1 -0.301 1.43E-03 0.320 8.82E-04
2477 ILMN_ .1788538 83988 NCALD -2.311 1.52E-21 0.716 2.59E-09
2478 ILMN_ .1788689 55023 PHIP -0.337 2.46E-05 0.716 1.32E-11
2479 ILMN_ .1788701 11168 PSIP1 -1.425 9.81E-18 1.272 2.58E-16
2480 ILMN_ .1788778 55752 Sep- 11 -0.587 1.25E-07 0.271 2.16E-03
2481 ILMN_ .1788783 9697 TRAM2 -0.404 7.93E-06 0.250 2.41E-03
2482 ILMN_ .1789240 64223 MLST8 -0.445 2.55E-05 0.416 7.70E-06
2483 ILMN_ .1789338 10174 SORBS3 -0.984 6.57E-13 0.300 8.34E-04
2484 ILMN_ .1789357 1747 DLX3 -0.470 1.07E-05 0.516 2.12E-06
2485 ILMN_ .1789394 117144 CATSPER1 -0.407 8.87E-06 0.254 2.66E-03
2486 ILMN_ .1789400 2306 FOXD2 -0.656 1.45E-08 0.703 4.02E-09
2487 ILMN_ .1789457 2794 GNL1 -0.248 1.69E-03 0.300 3.41E-04
2488 ILMN_ .1789502 2239 GPC4 -0.400 3.67E-05 0.488 1.24E-06
2489 ILMN_ .1789614 7178 TPT1 -0.447 6.81E-04 0.541 3.84E-05
2490 ILMN_ .1789627 5413 Sep-05 -1.795 5.68E-19 0.922 7.24E-12
2491 ILMN_ .1789702 2632 GBE1 -0.811 2.14E-10 0.533 7.52E-07
2492 ILMN_ .1790100 220042 Cl lorf82 -0.939 9.73E-12 0.275 3.18E-03
2493 ILMN_ .1790197 54621 FLJ20674 -0.536 1.12E-06 0.650 4.69E-08
2494 ILMN_ .1790352 80235 PIGZ -0.465 5.11E-06 0.504 1.86E-06
2495 ILMN_ .1790412 283876 FLJ39639 -0.650 2.07E-07 0.489 1.55E-05
2496 ILMN_ .1790461 84300 C6orfl25 -0.656 3.24E-09 0.600 1.92E-08
2497 ILMN_ .1790537 116028 C16orf75 -1.031 1.29E-13 0.354 1.08E-04
2498 ILMN_ .1790637 79703 Cl lorf80 -0.668 2.62E-09 0.614 1.18E-08
2499 ILMN_ .1790781 147015 DHRS13 -0.553 6.50E-07 0.626 6.07E-08
2500 ILMN_ .1790807 7508 XPC -0.382 7.40E-05 0.591 7.57E-08
2501 ILMN_ .1790953 1155 TBCB -0.519 2.13E-07 0.242 4.18E-03
2502 ILMN_ .1790962 126432 RINL -0.228 9.91E-03 0.357 1.07E-04
2503 ILMN_ .1791328 27347 STK39 -0.790 1.50E-10 0.401 3.45E-05
2504 ILMN_ .1791396 8214 DGCR6 -0.346 3.52E-05 0.856 1.79E-12
2505 ILMN_ .1791568 9702 CEP57 -0.510 1.65E-05 0.359 6.36E-04
2506 ILMN_ .1792305 24149 ZNF318 -0.776 2.56E-10 0.468 4.36E-06
2507 ILMN_ .1792389 494470 RNF165 -0.571 3.12E-06 0.341 1.35E-03 2508 ILMN_ .1792597 1427 CRYGS -0.355 1.39E-04 0.360 1.55E-04
2509 ILMN_ .1792669 3141 HLCS -0.499 4.18E-06 0.330 3.57E-04
2510 ILMN_ .1792748 1373 CPS1 -0.559 7.83E-08 0.372 2.34E-05
2511 ILMN_ .1793360 378708 APITD1 -1.047 4.43E-13 0.985 1.86E-12
2512 ILMN_ .1793549 5775 PTPN4 -0.351 4.38E-05 0.318 1.40E-04
2513 ILMN_ .1793572 114035 C21orf81 -0.609 2.66E-05 0.261 6.58E-03
2514 ILMN_ .1793615 10873 ME3 -0.858 1.82E-10 0.582 2.29E-07
2515 ILMN_ .1793743 84925 DIRC2 -0.264 2.96E-03 0.499 1.65E-06
2516 ILMN_ .1793859 217 ALDH2 -0.299 1.62E-04 0.450 5.90E-07
2517 ILMN_ .1793894 25847 ANAPC13 -0.221 5.24E-03 0.600 5.76E-09
2518 ILMN_ .1793966 51027 BOLA1 -0.441 1.95E-05 0.352 3.16E-04
2519 ILMN_ .1794132 4728 NDUFS8 -0.712 2.78E-11 0.404 1.91E-06
2520 ILMN_ .1794213 25864 ABHD14A -0.820 4.11E-12 0.293 2.02E-04
2521 ILMN_ .1794781 7410 VAV2 -0.398 4.64E-05 0.300 5.85E-04
2522 ILMN_ .1794825 224 ALDH3A2 -0.406 2.96E-05 0.255 2.99E-03
2523 ILMN_ .1795063 284273 ZADH2 -0.704 2.87E-08 0.310 1.43E-03
2524 ILMN_ .1795429 7414 VCL -0.790 1.23E-11 0.588 5.82E-09
2525 ILMN_ .1795937 7430 VIL2 -0.319 1.55E-04 0.347 7.74E-05
2526 ILMN_ .1795976 118980 SFXN2 -0.379 2.01E-04 0.285 3.68E-03
2527 ILMN_ .1796074 494514 C18orf56 -1.551 3.06E-18 0.323 2.52E-04
2528 ILMN_ .1796229 2260 FGFRl -0.450 5.54E-05 0.424 5.36E-05
2529 ILMN_ .1796751 27143 KIAA1274 -0.996 2.09E-12 0.324 6.68E-04
2530 ILMN_ .1796923 81691 LOC81691 -1.210 8.40E-16 0.470 9.72E-07
2531 ILMN_ .1797181 93622 LOC93622 -0.735 1.64E-11 0.304 1.54E-04
2532 ILMN_ .1797281 727851 LOC727851 -0.228 1.06E-02 0.263 4.31E-03
2533 ILMN_ .1797342 23048 FNBP1 -0.511 5.48E-08 0.453 6.92E-07
2534 ILMN_ .1797372 205428 C3orf58 -0.419 6.33E-05 0.254 6.63E-03
2535 ILMN_ .1797384 7390 UROS -0.566 1.23E-08 0.212 6.73E-03
2536 ILMN_ .1797813 23512 SUZ12 -0.449 1.61E-06 0.322 2.02E-04
2537 ILMN_ .1797822 23231 SEL1L3 -0.953 5.81E-12 0.729 2.32E-09
2538 ILMN_ .1797873 255239 ANKK1 -0.540 1.55E-04 0.254 4.50E-03
2539 ILMN_ .1797950 2135 EXTL2 -0.645 3.02E-09 0.293 2.60E-04
2540 ILMN_ .1797974 51390 AIG1 -1.713 3.64E-20 0.485 2.78E-07
2541 ILMN_ .1798006 148741 ANKRD35 -1.405 1.77E-15 0.274 4.78E-03
2542 ILMN_ .1798163 65109 UPF3B -0.418 2.83E-06 0.535 5.91E-08
2543 ILMN_ .1798210 144455 E2F7 -0.767 8.68E-10 1.253 7.61E-16
2544 ILMN_ .1798654 4175 MCM6 -1.022 6.77E-15 0.312 1.07E-04
2545 ILMN_ .1798874 51234 TMEM85 -0.771 l.OOE-10 0.269 1.46E-03
2546 ILMN_ .1798886 11051 NUDT21 -0.831 3.10E-10 0.276 3.67E-03
2547 ILMN_ .1798957 51275 C12orf47 -0.323 5.20E-05 0.483 1.62E-07
2548 ILMN_ .1799015 5827 PXMP2 -1.347 5.14E-16 0.554 1.76E-07
2549 ILMN_ .1799106 64757 MOSC1 -1.778 7.41E-20 0.368 4.18E-05
2550 ILMN_ .1799113 51134 CCDC41 -0.661 4.81E-09 0.414 1.61E-05
2551 ILMN_ .1799128 10463 SLC30A9 -0.661 l.OOE-10 0.381 5.58E-06 2552 ILMN_ .1799207 642691 LOC642691 -0.551 2.72E-08 0.557 3.68E-08
2553 ILMN_ .1799320 85026 C9orf37 -0.364 1.35E-04 0.342 2.64E-04
2554 ILMN_ .1799516 23234 DNAJC9 -0.651 4.57E-10 0.455 3.50E-07
2555 ILMN_ .1799589 10811 NOXA1 -0.774 1.54E-08 0.496 2.17E-05
2556 ILMN_ .1799604 54940 OCIAD1 -0.317 2.82E-04 0.300 4.77E-04
2557 ILMN_ .1799939 138474 TAF1L -0.338 4.20E-03 0.405 7.28E-04
2558 ILMN_ .1800008 38 AC ATI -0.691 7.59E-10 0.270 1.73E-03
2559 ILMN_ .1800253 7552 ZNF711 -0.273 3.54E-03 0.251 6.57E-03
2560 ILMN_ .1800354 1471 CST3 -0.551 4.12E-08 0.233 2.88E-03
2561 ILMN_ .1800465 654042 LOC654042 -0.323 2.57E-04 0.232 6.58E-03
2562 ILMN_ .1800530 116987 CENTG2 -1.116 1.17E-13 0.295 1.41E-03
2563 ILMN_ .1800611 55722 CEP72 -0.535 3.91E-08 0.490 2.63E-07
2564 ILMN_ .1800626 27244 SESN1 -0.243 1.04E-02 0.675 3.54E-09
2565 ILMN_ .1800659 5236 PGM1 -1.041 2.84E-14 0.474 7.14E-07
2566 ILMN_ .1800796 6167 RPL37 -0.579 8.58E-07 0.324 2.95E-04
2567 ILMN_ .1800837 10428 CFDP1 -0.342 6.92E-05 0.335 1.09E-04
2568 ILMN_ .1800942 200845 KCTD6 -0.336 3.61E-04 0.293 1.34E-03
2569 ILMN_ .1800958 65062 ALS2CR4 -0.522 5.34E-07 0.506 5.72E-07
2570 ILMN_ .1801101 3104 ZBTB48 -0.272 2.31E-03 0.302 1.11E-03
2571 ILMN_ .1801303 279 AMY2A -0.527 1.34E-05 0.370 4.80E-04
2572 ILMN_ .1801348 2806 GOT2 -0.590 3.69E-08 0.540 1.64E-07
2573 ILMN_ .1801387 8089 YEATS4 -0.803 2.27E-10 0.375 8.71E-05
2574 ILMN_ .1801491 1836 SLC26A2 -0.362 8.35E-05 0.246 4.16E-03
2575 ILMN_ .1801606 51321 AMZ2 -0.328 1.32E-04 0.224 5.84E-03
2576 ILMN_ .1801845 10126 DNAL4 -0.431 1.08E-05 1.213 3.72E-15
2577 ILMN_ .1801853 283417 DPY19L2 -0.666 1.05E-08 0.375 7.14E-05
2578 ILMN_ .1802157 9984 THOC1 -0.469 1.48E-06 0.243 3.46E-03
2579 ILMN_ .1802615 1021 CDK6 -1.083 4.34E-15 0.912 4.43E-13
2580 ILMN_ .1803018 90990 KIFC2 -1.114 3.44E-11 0.353 2.42E-03
2581 ILMN_ .1803045 114791 TUBGCP5 -0.425 6.43E-06 0.258 1.88E-03
2582 ILMN_ .1803094 80310 PDGFD -1.193 1.85E-13 0.436 3.96E-05
2583 ILMN_ .1803192 79968 WDR76 -0.834 5.55E-10 0.492 5.19E-06
2584 ILMN_ .1803392 30851 TAX1BP3 -0.265 8.89E-04 0.347 5.56E-05
2585 ILMN_ .1803813 28990 ASTE1 -0.773 3.97E-11 0.583 1.55E-08
2586 ILMN_ .1803838 84518 CNFN -1.270 8.92E-16 0.775 1.16E-10
2587 ILMN_ .1804090 1468 SLC25A10 -1.757 2.94E-17 0.525 2.85E-06
2588 ILMN_ .1804150 11112 HIBADH -0.472 1.39E-07 0.349 2.64E-05
2589 ILMN_ .1804263 7629 ZNF76 -0.222 8.36E-03 0.215 8.00E-03
2590 ILMN_ .1804328 11059 WWP1 -0.210 7.16E-03 0.350 4.46E-05
2591 ILMN_ 1804419 4033 LRMP -1.495 4.12E-17 0.323 4.57E-04
2592 ILMN_ .1804737 55225 RAVER2 -0.628 2.01E-08 0.503 7.03E-07
2593 ILMN_ 1804834 221443 C6orfl30 -0.240 5.99E-03 0.367 1.10E-04
2594 ILMN_ .1805271 170960 ZNF721 -0.452 2.14E-06 0.317 1.88E-04
2595 ILMN_ 1805474 128061 Clorfl31 -0.236 1.43E-03 0.261 7.08E-04 2596 ILMN_ .1805590 51691 LSM8 -0.263 1.19E-03 0.359 3.24E-05
2597 ILMN_ .1805726 654069 LOC654069 -0.217 9.85E-03 0.233 7.34E-03
2598 ILMN_ .1805796 114984 FLYWCH2 -0.396 4.60E-05 0.457 7.93E-06
2599 ILMN_ .1805807 7781 SLC30A3 -0.288 4.98E-03 0.995 2.92E-11
2600 ILMN_ .1805828 7443 VRK1 -0.672 2.88E-10 0.208 7.14E-03
2601 ILMN_ .1805973 2842 GPR19 -0.272 2.59E-03 0.501 1.17E-06
2602 ILMN_ .1806003 79925 SPEF2 -0.488 2.92E-05 0.504 1.77E-05
2603 ILMN_ .1806022 647947 LOC647947 -0.290 4.73E-03 0.340 1.10E-03
2604 ILMN_ .1806037 7083 TK1 -1.040 9.37E-14 1.301 5.00E-16
2605 ILMN_ .1806040 7298 TYMS -1.478 7.97E-18 1.020 9.92E-14
2606 ILMN_ .1806408 37 ACADVL -0.271 2.46E-04 0.346 1.89E-05
2607 ILMN_ .1806415 25809 TTLL1 -0.689 4.15E-08 0.279 4.44E-03
2608 ILMN_ .1806456 80127 C14orf45 -0.455 3.13E-04 0.414 6.72E-05
2609 ILMN_ .1806603 55897 MESP1 -1.030 2.50E-12 0.649 5.36E-08
2610 ILMN_ .1806710 83715 ESPN -0.297 2.16E-03 0.379 3.32E-05
2611 ILMN_ .1806818 4172 MCM3 -1.008 8.98E-13 0.685 3.71E-09
2612 ILMN_ .1806825 145508 C14orfl45 -1.053 4.08E-13 0.588 1.29E-07
2613 ILMN_ .1806999 80776 B9D2 -0.339 2.71E-04 0.471 4.50E-06
2614 ILMN_ .1807397 4711 NDUFB5 -0.377 1.76E-05 0.473 5.79E-07
2615 ILMN_ .1807501 84296 GINS4 -0.893 3.32E-11 0.616 6.45E-08
2616 ILMN_ .1807611 9360 PPIG -0.248 2.68E-03 0.313 2.59E-04
2617 ILMN_ .1807710 3094 HINT1 -0.373 1.88E-05 0.338 8.95E-05
2618 ILMN_ .1807767 23199 KIAA0182 -1.759 1.28E-17 0.504 6.90E-06
2619 ILMN_ .1807994 57092 PCNP -0.205 8.76E-03 0.342 4.02E-05
2620 ILMN_ .1808333 5510 PPP1R7 -0.412 4.64E-05 0.509 2.68E-06
2621 ILMN_ .1808568 29920 PYCR2 -0.229 3.27E-03 0.271 6.11E-04
2622 ILMN_ .1808584 116228 FAM36A -0.706 3.75E-09 0.240 8.84E-03
2623 ILMN_ .1808636 55132 LARP1B -0.573 7.84E-08 0.717 1.21E-09
2624 ILMN_ .1808712 9810 RNF40 -0.250 2.38E-03 0.241 4.08E-03
2625 ILMN_ .1808783 55342 STRBP -0.980 7.70E-14 0.241 2.33E-03
2626 ILMN_ .1809040 26119 LDLRAP1 -0.577 4.14E-08 0.313 4.89E-04
2627 ILMN_ .1809292 83943 IMMP2L -0.550 3.54E-08 0.341 6.35E-05
2628 ILMN_ .1809477 23589 CARHSP1 -1.128 9.03E-15 1.580 1.96E-18
2629 ILMN_ .1809590 51659 GINS2 -1.300 2.93E-14 0.307 2.10E-03
2630 ILMN_ .1810147 147807 ZNF524 -0.399 7.51E-06 0.337 5.91E-05
2631 ILMN_ .1810199 80150 ASRGL1 -0.466 1.48E-03 0.924 6.41E-09
2632 ILMN_ .1810228 8458 TTF2 -0.761 1.13E-10 0.618 9.77E-09
2633 ILMN_ .1810235 90423 ATP6V1E2 -0.214 8.11E-03 0.328 1.05E-04
2634 ILMN_ .1810901 10535 RNASEH2A -1.168 1.16E-14 1.114 3.09E-14
2635 ILMN_ .1810922 5116 PCNT -1.113 9.88E-16 0.680 1.55E-10
2636 ILMN_ .1810962 5796 PTPRK -0.263 2.21E-03 0.360 1.12E-04
2637 ILMN_ .1811006 79733 E2F8 -1.231 2.72E-13 0.977 2.48E-11
2638 ILMN_ .1811167 148870 CCDC27 -0.270 3.60E-03 0.460 7.40E-06
2639 ILMN_ .1811373 9917 FAM20B -0.774 1.76E-10 0.358 1.23E-04 2640 ILMN_ .1811468 79191 IRX3 -2.159 1.83E-21 0.442 6.86E-06
2641 ILMN_ .1811551 51071 DERA -0.647 4.16E-08 0.325 8.33E-04
2642 ILMN_ .1811555 375757 C9orfl l9 -0.325 2.31E-04 0.484 9.35E-07
2643 ILMN_ .1811624 63892 THADA -0.379 1.12E-05 0.637 1.89E-09
2644 ILMN_ .1811648 79877 DCAKD -1.165 1.11E-14 0.895 6.65E-12
2645 ILMN_ .1811921 1465 CSRP1 -0.619 5.41E-09 0.529 6.46E-08
2646 ILMN_ .1811933 6470 SHMT1 -0.869 1.58E-10 0.351 5.19E-04
2647 ILMN_ .1812031 5064 PALM -0.644 2.16E-09 0.632 4.95E-09
2648 ILMN_ .1812191 113246 C12orf57 -0.878 9.16E-12 0.554 1.39E-07
2649 ILMN_ .1812489 64793 CCDC21 -0.635 1.01E-07 0.365 1.23E-04
2650 ILMN_ .1812503 5255 PHKA1 -0.434 3.99E-06 0.382 1.35E-05
2651 ILMN_ .1812856 90204 ZSWIM1 -0.208 9.94E-03 0.296 6.69E-04
2652 ILMN_ .1812949 127255 LRRC44 -0.287 6.40E-03 0.281 5.07E-03
2653 ILMN_ .1812968 54345 SOX 18 -0.317 6.05E-04 0.224 7.29E-03
2654 ILMN_ .1813028 23468 CBX5 -0.699 7.27E-10 0.438 3.07E-06
2655 ILMN_ .1813091 400 ARL1 -0.318 2.88E-04 0.350 1.24E-04
2656 ILMN_ .1813475 8924 HERC2 -0.655 2.34E-10 0.242 1.72E-03
2657 ILMN_ .1813544 5019 OXCT1 -1.332 1.54E-16 0.496 4.07E-07
2658 ILMN_ .1813581 1268 CNR1 -0.258 1.02E-02 0.683 1.56E-09
2659 ILMN_ .1813746 7464 COR02A -0.604 2.79E-08 0.240 6.35E-03
2660 ILMN_ .1814120 55825 PECR -0.802 5.38E-10 0.651 4.28E-08
2661 ILMN_ .1814213 130814 PQLC3 -0.585 8.24E-09 0.210 8.40E-03
2662 ILMN_ .1814230 4515 MTCP1 -0.756 4.60E-11 0.849 1.68E-12
2663 ILMN_ .1814247 10732 TCFL5 -1.409 3.34E-17 0.568 4.53E-08
2664 ILMN_ .1814281 57405 SPC25 -1.447 2.54E-14 0.493 2.37E-05
2665 ILMN_ .1814526 120 ADD3 -1.012 1.68E-13 0.893 3.30E-12
2666 ILMN_ .1814629 340554 ZC3H12B -0.280 4.12E-03 0.518 4.08E-07
2667 ILMN_ .1815010 50862 RNF141 -0.369 2.45E-04 0.506 2.97E-06
2668 ILMN_ .1815154 4628 MYH10 -0.920 2.22E-12 0.908 3.58E-12
2669 ILMN_ .1815319 146223 CMTM4 -1.064 8.17E-14 0.499 4.39E-07
2670 ILMN_ .1815500 3710 ITPR3 -0.822 7.14E-11 0.864 1.15E-11
2671 ILMN_ .1815682 56941 C3orf37 -0.331 1.92E-04 0.594 3.51E-08
2672 ILMN_ .1815705 54585 LZTFL1 -0.854 2.97E-12 0.282 7.11E-04
2673 ILMN_ .1815951 78991 PCYOX1L -0.578 3.47E-07 0.348 4.40E-04
2674 ILMN_ .1874530 81624 DIAPH3 -0.920 8.03E-13 0.583 2.40E-08
2675 ILMN_ .1882764 730358 LOC730358 -0.273 2.19E-03 0.504 5.20E-07
2676 ILMN_ .1887174 23514 KIAA0146 -0.545 1.01E-07 0.345 1.36E-04
2677 ILMN_ .2041327 51253 MRPL37 -0.692 1.06E-09 0.496 6.30E-07
2678 ILMN_ .2042595 5108 PCM1 -0.828 1.23E-11 0.252 2.48E-03
2679 ILMN_ .2043452 2178 FANCE -0.672 8.22E-10 0.280 9.57E-04
2680 ILMN_ .2043615 339229 C17orf90 -0.404 5.09E-06 0.519 9.16E-08
2681 ILMN_ .2044927 6048 RNF5 -0.555 1.58E-08 0.367 2.63E-05
2682 ILMN_ .2047112 25911 RP11-529110.4 -0.355 5.97E-04 0.380 1.03E-04
2683 ILMN_ .2048607 122416 ANKRD9 -0.223 7.13E-03 0.289 1.06E-03 2684 ILMN .2048700 29028 ATAD2 -1.134 4.90E-15 0.828 1.34E-11
2685 ILMN .2049303 1632 DCI -0.867 3.21E-13 0.712 6.11E-11
2686 ILMN .2050023 374969 CCDC23 -0.322 9.50E-05 0.407 4.87E-06
2687 ILMN .2050813 1047 CLGN -1.188 3.31E-14 1.444 1.70E-16
2688 ILMN .2051381 126133 ALDH16A1 -0.545 1.44E-07 0.449 1.16E-06
2689 ILMN .2052598 83787 ARMC10 -0.296 8.87E-04 0.231 8.42E-03
2690 ILMN .2053679 34 ACADM -0.321 8.03E-05 0.535 3.81E-08
2691 ILMN .2054233 26054 SENP6 -0.830 6.74E-10 0.438 3.92E-05
2692 ILMN .2055760 80856 KIAA1715 -1.139 5.43E-12 0.484 2.94E-05
2693 ILMN .2059452 6558 SLC12A2 -0.454 9.50E-05 0.578 1.39E-06
2694 ILMN .2062468 3490 IGFBP7 -1.252 3.60E-14 0.266 4.96E-03
2695 ILMN .2064694 6786 STIM1 -0.518 2.38E-05 0.350 2.03E-03
2696 ILMN .2064917 55109 AGGF1 -0.495 3.02E-08 0.315 6.44E-05
2697 ILMN .2066756 54892 NCAPG2 -1.245 1.22E-14 0.450 1.38E-05
2698 ILMN .2068747 4942 OAT -0.535 2.07E-06 0.386 4.53E-05
2699 ILMN .2069632 121355 GTSF1 -0.804 5.11E-12 0.505 9.08E-08
2700 ILMN .2070210 79596 RNF219 -0.229 4.02E-03 0.364 3.44E-05
2701 ILMN .2072541 22841 RAB11FIP2 -0.243 4.38E-03 0.363 6.43E-05
2702 ILMN .2073184 53637 S1PR5 -1.060 3.65E-14 0.242 2.30E-03
2703 ILMN .2073592 23066 CAND2 -0.547 9.01E-07 0.562 5.23E-07
2704 ILMN .2075334 8364 HIST1H4C -1.898 4.80E-21 0.288 5.83E-04
2705 ILMN .2078466 199221 DZIP1L -0.799 3.99E-10 0.257 4.86E-03
2706 ILMN .2081883 124152 IQCK -0.382 1.08E-04 0.455 1.26E-05
2707 ILMN .2081988 10314 LANCL1 -0.822 3.10E-11 0.250 3.32E-03
2708 ILMN .2082209 84969 C20orfl00 -1.210 2.22E-16 1.551 3.29E-19
2709 ILMN .2083588 130502 TTC32 -0.246 4.94E-03 0.381 7.14E-05
2710 ILMN .2085236 28966 SNX24 -0.451 3.02E-06 0.321 3.27E-04
2711 ILMN .2085446 93474 ZNF670 -0.780 5.93E-10 0.761 5.62E-10
2712 ILMN .2087692 79901 CYBRD1 -0.587 9.18E-08 0.961 3.31E-12
2713 ILMN .2088124 201799 TMEM154 -1.108 3.74E-14 0.967 7.54E-13
2714 ILMN .2088437 1524 CX3CR1 -1.180 7.40E-16 1.486 1.61E-18
2715 ILMN .2089458 163786 SASS6 -0.893 1.24E-10 0.298 8.04E-04
2716 ILMN .2090802 84283 TMEM79 -0.380 1.25E-04 1.070 3.89E-13
2717 ILMN .2093231 23559 WBP1 -0.432 1.53E-05 0.328 4.19E-04
2718 ILMN .2094061 3613 IMPA2 -1.855 2.64E-21 0.952 1.17E-13
2719 ILMN .2094106 51144 HSD17B12 -0.571 5.34E-09 0.206 7.22E-03
2720 ILMN .2094313 29800 ZDHHC1 -0.409 1.97E-05 0.768 l.OlE-10
2721 ILMN .2095273 57577 KIAA1407 -0.402 1.44E-05 0.295 6.41E-04
2722 ILMN .2096654 54939 COMMD4 -0.556 1.46E-08 0.389 1.10E-05
2723 ILMN .2096719 2869 GRK5 -0.342 1.18E-03 0.583 1.07E-06
2724 ILMN .2101526 79017 GGCT -0.570 1.95E-08 0.382 2.07E-05
2725 ILMN .2103547 440270 GOLGA8B -0.347 1.10E-02 0.551 1.71E-04
2726 ILMN .2104967 10224 ZNF443 -0.624 4.91E-09 0.604 1.40E-08
2727 ILMN .2105923 83695 C12orf32 -0.616 3.27E-09 0.236 3.71E-03 2728 ILMN .2108735 1917 EEF1A2 -1.687 3.35E-17 1.396 3.03E-15
2729 ILMN .2109416 256236 NAPSB -0.371 6.66E-05 0.808 1.02E-10
2730 ILMN .2110167 64425 POLR1E -0.676 4.25E-09 0.253 3.68E-03
2731 ILMN .2111932 347735 SERINC2 -1.020 9.10E-13 0.404 3.94E-05
2732 ILMN .2112599 29105 C16orf80 -0.642 7.37E-10 0.701 1.51E-10
2733 ILMN .2117330 4708 NDUFB2 -0.470 6.35E-08 0.235 1.47E-03
2734 ILMN .2117987 7027 TFDP1 -0.688 9.79E-10 0.228 6.06E-03
2735 ILMN .2120072 84140 FLJ13305 -0.473 7.88E-05 0.434 4.47E-05
2736 ILMN .2120555 107 ADCY1 -0.231 6.53E-03 0.477 2.24E-06
2737 ILMN .2123415 656 BMP8B -2.171 7.69E-21 0.235 8.23E-03
2738 ILMN .2124361 116842 LEAP2 -0.422 6.73E-05 0.506 3.28E-06
2739 ILMN .2128770 30850 CDR2L -0.691 2.80E-09 0.964 2.26E-12
2740 ILMN .2128967 64776 Cl lorfl -0.751 2.10E-10 0.589 8.04E-09
2741 ILMN .2130635 80020 FOXRED2 -0.954 3.19E-12 0.409 2.73E-05
2742 ILMN .2131880 84661 DPY30 -0.385 1.10E-05 0.248 2.36E-03
2743 ILMN .2132809 9639 ARHGEF10 -0.901 5.33E-13 0.562 2.51E-08
2744 ILMN .2134039 57001 ACN9 -0.964 8.16E-13 0.345 8.81E-05
2745 ILMN .2134062 221120 ALKBH3 -0.446 1.25E-06 0.471 7.41E-07
2746 ILMN .2134555 51133 KCTD3 -0.520 5.08E-07 0.230 8.64E-03
2747 ILMN .2134855 728758 LOC728758 -0.560 8.53E-07 0.272 5.37E-03
2748 ILMN .2135798 126382 NR2C2AP -0.927 4.09E-12 0.663 7.55E-09
2749 ILMN .2136446 8727 CTNNAL1 -1.323 3.52E-15 0.944 1.03E-11
2750 ILMN .2137066 7553 ZNF7 -0.267 1.24E-03 0.242 2.43E-03
2751 ILMN .2138754 55064 C9orf68 -0.223 1.18E-02 0.318 5.61E-04
2752 ILMN .2140799 196792 FAM24B -0.406 9.55E-06 0.891 1.88E-12
2753 ILMN .2141452 6142 RPL18A -0.271 1.05E-03 0.229 3.79E-03
2754 ILMN .2145396 22977 AKR7A3 -1.385 2.25E-16 0.574 5.07E-08
2755 ILMN .2145997 6671 SP4 -0.585 1.41E-06 0.412 1.87E-04
2756 ILMN .2146389 84466 MEGF10 -0.428 1.53E-04 0.412 6.22E-06
2757 ILMN .2147105 440348 LOC440348 -0.329 3.29E-03 0.415 3.80E-04
2758 ILMN .2147424 5273 SERPWB 10 -1.759 3.44E-19 0.253 3.78E-03
2759 ILMN .2148150 494143 CHAC2 -0.726 1.66E-09 0.440 6.25E-06
2760 ILMN .2148796 84057 MND1 -1.208 7.34E-16 0.653 1.25E-09
2761 ILMN .2149164 6422 SFRP1 -0.656 8.26E-09 0.903 2.30E-12
2762 ILMN .2151488 80010 RMI1 -0.689 4.80E-10 0.401 1.14E-05
2763 ILMN .2153485 349565 NMNAT3 -1.396 6.36E-18 0.725 6.75E-11
2764 ILMN .2154053 2531 FVT1 -0.386 3.02E-05 0.486 1.17E-06
2765 ILMN .2156936 51097 SCCPDH -0.827 2.16E-10 0.424 2.20E-05
2766 ILMN .2157240 55329 MNS1 -0.813 1.13E-11 1.015 1.68E-14
2767 ILMN .2158336 56904 SH3GLB2 -0.682 7.07E-10 0.450 1.72E-06
2768 ILMN .2159290 441376 LOC441376 -0.281 1.32E-03 0.285 1.00E-03
2769 ILMN .2159300 399726 C10orfl l4 -1.906 1.02E-18 0.472 1.36E-05
2770 ILMN .2159471 492303 LOC492303 -0.217 1.23E-02 0.345 2.10E-04
2771 ILMN .2160929 2237 FENl -0.943 2.72E-12 0.739 7.17E-10 2772 ILMN .2161508 57157 PHTF2 -0.298 2.46E-03 0.262 5.88E-03
2773 ILMN .2162234 4750 NEK1 -0.385 5.32E-05 0.825 9.32E-11
2774 ILMN .2163070 80759 KHDC1 -0.212 7.08E-03 0.983 8.57E-14
2775 ILMN .2167922 57570 TRMT5 -0.512 2.87E-07 0.347 1.35E-04
2776 ILMN .2168347 2057 EPOR -0.523 2.49E-08 0.444 6.06E-07
2777 ILMN .2171295 5218 PFTKl -0.212 1.26E-02 0.272 1.67E-03
2778 ILMN .2172969 29091 STXBP6 -0.877 9.90E-10 0.295 5.58E-03
2779 ILMN .2173919 4649 MY09A -0.573 1.23E-08 0.376 2.26E-05
2780 ILMN .2175131 51522 TMEM14C -0.878 3.89E-13 0.954 7.46E-14
2781 ILMN .2179726 90835 C16orf93 -2.126 1.34E-20 0.768 5.11E-10
2782 ILMN .2181432 147841 SPC24 -1.538 8.69E-19 0.258 1.45E-03
2783 ILMN .2181968 867 CBL -0.617 3.07E-09 0.329 1.33E-04
2784 ILMN .2183519 170393 C10orf91 -0.345 4.01E-04 0.244 5.51E-03
2785 ILMN .2183728 27152 INTU -0.252 4.11E-03 0.383 7.16E-05
2786 ILMN .2184184 301 ANXA1 -0.632 4.61E-09 1.301 1.00E-16
2787 ILMN .2186597 79897 RPP21 -0.230 6.52E-03 0.609 8.67E-09
2788 ILMN .2188264 3491 CYR61 -0.211 1.14E-02 0.602 1.40E-08
2789 ILMN .2188374 11260 XPOT -0.465 3.27E-05 0.573 1.67E-06
2790 ILMN .2188722 2744 GLS -0.798 1.86E-10 0.337 3.74E-04
2791 ILMN .2191436 5422 POLA1 -1.131 1.90E-14 0.825 3.69E-11
2792 ILMN .2191929 54942 C9orf6 -0.258 9.15E-04 0.514 5.58E-08
2793 ILMN .2193315 90141 C14orfl43 -0.640 6.12E-08 0.633 2.07E-08
2794 ILMN .2193752 153364 MBLAC2 -0.749 4.34E-10 0.225 7.61E-03
2795 ILMN .2194828 79447 C16orf53 -1.147 4.71E-15 0.254 1.88E-03
2796 ILMN .2196550 80183 C13orfl8 -0.668 9.11E-09 0.626 3.54E-08
2797 ILMN .2196984 11339 OIP5 -1.233 1.56E-15 0.265 1.53E-03
2798 ILMN .2197519 199692 ZNF627 -0.242 2.46E-03 0.318 1.56E-04
2799 ILMN .2198185 8269 CXorfl2 -0.346 3.16E-04 0.318 7.88E-04
2800 ILMN .2199389 7433 VIPR1 -0.573 6.64E-07 0.316 1.46E-03
2801 ILMN .2200331 3014 H2AFX -1.158 2.41E-14 0.449 5.94E-06
2802 ILMN .2200503 56954 NIT2 -0.221 8.23E-03 0.281 1.48E-03
2803 ILMN .2200880 195828 ZNF367 -0.682 2.18E-08 0.292 1.98E-03
2804 ILMN .2201533 254863 C17orf61 -0.465 4.42E-06 0.281 1.75E-03
2805 ILMN .2201580 2946 GSTM2 -0.548 1.55E-08 0.328 8.17E-05
2806 ILMN .2202637 1407 CRY1 -0.325 5.61E-04 0.552 4.07E-07
2807 ILMN .2204545 6484 ST3GAL4 -1.294 4.68E-15 0.290 1.50E-03
2808 ILMN .2204754 56255 TMX4 -0.906 5.87E-13 0.784 2.14E-11
2809 ILMN .2205032 57692 MAGEE1 -0.304 2.62E-03 0.286 4.84E-03
2810 ILMN .2206098 83734 ATG10 -0.379 2.79E-05 0.332 1.80E-04
2811 ILMN .2208903 1043 CD52 -0.480 6.01E-06 0.503 2.47E-06
2812 ILMN .2209551 284367 SIGLECP3 -0.451 8.91E-06 0.267 2.85E-03
2813 ILMN .2210129 5557 PRIM1 -1.006 1.30E-12 0.873 3.35E-11
2814 ILMN .2211780 291 SLC25A4 -0.226 3.83E-03 1.312 8.26E-17
2815 ILMN .2212714 55116 TMEM39B -0.608 3.20E-09 0.411 4.52E-06 2816 ILMN .2214098 54841 BIVM -0.928 5.80E-13 0.223 5.79E-03
2817 ILMN .2214278 84250 ANKRD32 -0.681 2.39E-09 0.729 5.25E-10
2818 ILMN .2215043 140545 RNF32 -0.288 6.40E-03 0.372 3.18E-04
2819 ILMN .2215824 84210 ANKRD20A1 -1.018 2.15E-11 0.448 1.10E-05
2820 ILMN .2216582 4066 LYL1 -0.854 3.52E-13 0.243 1.21E-03
2821 ILMN .2217329 285148 IAH1 -0.317 2.88E-04 0.243 3.38E-03
2822 ILMN .2217935 5981 RFC1 -0.511 5.40E-07 0.481 1.70E-06
2823 ILMN .2219466 9582 APOBEC3B -0.320 4.46E-04 0.268 2.31E-03
2824 ILMN .2219512 261734 NPHP4 -0.836 5.81E-11 0.335 3.68E-04
2825 ILMN .2221673 54529 ASNSD1 -0.456 1.47E-06 0.564 5.24E-08
2826 ILMN .2222880 284439 SLC25A42 -0.963 3.27E-12 0.642 2.11E-08
2827 ILMN .2223010 7411 VBP1 -0.492 4.28E-07 0.375 3.72E-05
2828 ILMN .2223380 23398 PPWD1 -0.270 2.09E-03 0.252 3.57E-03
2829 ILMN .2223903 5480 PPIC -0.360 3.86E-05 0.624 6.38E-09
2830 ILMN .2224486 57415 C3orfl4 -0.321 7.01E-05 0.373 1.22E-05
2831 ILMN .2224833 79602 ADIPOR2 -0.274 1.71E-03 0.294 9.72E-04
2832 ILMN .2225537 22949 PTGR1 -0.436 1.25E-05 0.783 3.97E-10
2833 ILMN .2225577 134359 C5orf37 -0.378 5.88E-06 0.453 4.90E-07
2834 ILMN .2225595 27034 ACAD8 -0.314 5.50E-04 0.312 6.31E-04
2835 ILMN .2226628 7738 ZNF184 -0.385 4.62E-04 0.379 3.02E-04
2836 ILMN .2227533 84836 ABHD14B -0.519 3.09E-07 0.457 3.67E-06
2837 ILMN .2228180 4482 MSRA -0.340 1.17E-04 0.290 9.26E-04
2838 ILMN .2229940 84279 C2orf7 -1.128 9.74E-13 0.464 2.23E-05
2839 ILMN .2230683 55536 CDCA7L -1.177 4.10E-14 0.335 4.82E-04
2840 ILMN .2232463 80117 ARL14 -0.353 8.68E-04 0.277 6.30E-03
2841 ILMN .2234970 29985 SLC39A3 -0.692 2.86E-09 0.358 1.34E-04
2842 ILMN .2235602 284992 CCDC150 -0.294 5.59E-03 0.358 7.86E-04
2843 ILMN .2246328 26191 PTPN22 -1.518 2.03E-16 1.139 2.72E-13
2844 ILMN .2246510 7248 TSC1 -0.256 2.35E-03 0.451 2.43E-06
2845 ILMN .2246956 596 BCL2 -1.087 2.75E-14 0.376 2.21E-05
2846 ILMN .2249018 389816 LOC389816 -1.719 1.47E-19 1.465 4.45E-18
2847 ILMN .2250923 27086 FOXP1 -0.521 6.17E-06 0.339 1.13E-03
2848 ILMN .2264625 25836 NIPBL -0.383 1.05E-04 0.665 1.08E-08
2849 ILMN .2280568 375248 ANKRD36 -1.142 7.64E-12 0.370 3.76E-04
2850 ILMN .2282077 142678 MIB2 -0.526 3.53E-07 0.471 2.68E-06
2851 ILMN .2282959 1763 DNA2 -0.738 2.77E-11 0.577 4.43E-09
2852 ILMN .2285996 9768 KIAA0101 -1.279 1.16E-16 1.285 1.11E-16
2853 ILMN .2295987 55672 NBPF1 -0.369 5.68E-05 0.578 4.83E-08
2854 ILMN .2303166 55796 MBNL3 -0.737 1.36E-10 0.512 2.20E-07
2855 ILMN .2307450 55900 ZNF302 -0.341 9.01E-05 0.811 2.69E-11
2856 ILMN .2309926 79683 ZDHHC14 -0.240 1.25E-02 0.514 3.93E-06
2857 ILMN .2310296 54058 C21orf58 -1.701 4.60E-17 0.431 5.24E-05
2858 ILMN .2310909 489 ATP2A3 -0.319 1.07E-03 0.254 5.38E-03
2859 ILMN .2315569 29104 N6AMT1 -0.420 1.12E-05 0.219 7.14E-03 2860 ILMN .2316918 53354 PANK1 -0.865 3.87E-11 0.791 2.46E-10
2861 ILMN .2317618 6941 TCF19 -0.804 3.45E-09 0.764 6.52E-09
2862 ILMN .2320349 23621 BACE1 -0.621 3.77E-08 0.829 7.92E-11
2863 ILMN .2320480 400464 LOC400464 -0.491 7.15E-06 0.352 3.63E-04
2864 ILMN .2321064 581 BAX -0.392 2.55E-04 0.287 4.88E-03
2865 ILMN .2321416 1729 DIAPH1 -0.752 6.93E-11 0.263 1.56E-03
2866 ILMN .2325008 79665 DHX40 -0.317 2.84E-04 0.270 9.81E-04
2867 ILMN .2326713 977 CD151 -0.245 2.19E-03 0.485 1.33E-07
2868 ILMN .2330861 10051 SMC4 -1.096 2.01E-13 0.497 1.43E-06
2869 ILMN .2332795 7564 ZNF16 -0.340 4.30E-04 0.549 1.88E-07
2870 ILMN .2333766 9677 HISPPD2A -0.692 5.90E-09 0.509 2.07E-06
2871 ILMN .2334205 54821 ERCC6L -1.118 5.44E-13 0.256 6.26E-03
2872 ILMN .2337835 7569 ZNF182 -0.236 3.65E-03 0.356 6.57E-05
2873 ILMN .2337941 10920 COPS8 -0.306 1.22E-04 0.412 3.07E-06
2874 ILMN .2339028 5310 PKD1 -0.290 2.99E-04 0.270 6.39E-04
2875 ILMN .2343048 23457 ABCB9 -0.488 1.02E-05 0.818 3.93E-11
2876 ILMN .2344850 9559 VPS26A -0.188 1.07E-02 0.287 2.95E-04
2877 ILMN .2344907 286151 FBX043 -0.961 1.09E-11 0.348 4.45E-04
2878 ILMN .2346997 51715 RAB23 -0.479 5.93E-07 0.790 3.80E-11
2879 ILMN .2348503 10450 PPIE -0.341 2.29E-04 0.328 3.63E-04
2880 ILMN .2349129 10072 DPP3 -0.351 5.72E-05 0.374 3.38E-05
2881 ILMN .2350801 123096 SLC25A29 -0.632 8.63E-08 0.445 7.57E-06
2882 ILMN .2354237 10038 PARP2 -0.862 8.01E-11 0.651 2.11E-08
2883 ILMN .2355042 23059 CLUAP1 -0.537 4.23E-08 0.369 2.10E-05
2884 ILMN .2359453 51614 ERGIC3 -0.290 9.72E-04 0.267 1.66E-03
2885 ILMN .2361163 23648 SSBP3 -0.592 1.49E-08 0.667 1.20E-09
2886 ILMN .2361603 57447 NDRG2 -0.895 5.71E-12 0.382 3.64E-05
2887 ILMN .2361862 7436 VLDLR -1.571 2.51E-18 0.360 6.69E-05
2888 ILMN .2362549 11130 ZWINT -1.163 1.57E-15 0.454 5.89E-07
2889 ILMN .2363065 10313 RTN3 -0.841 5.58E-12 0.759 6.35E-11
2890 ILMN .2364072 1187 CLCNKA -0.331 4.71E-04 0.284 1.09E-03
2891 ILMN .2364088 54960 GEMIN8 -0.499 3.46E-07 0.227 5.72E-03
2892 ILMN .2364674 83707 TRPT1 -0.826 1.14E-11 0.592 1.40E-08
2893 ILMN .2366246 10483 SEC23B -0.459 3.69E-07 0.347 2.90E-05
2894 ILMN .2367113 839 CASP6 -0.679 1.24E-07 0.387 4.26E-04
2895 ILMN .2367215 5547 PRCP -0.515 1.60E-07 0.343 8.09E-05
2896 ILMN .2368718 79019 CENPM -1.551 6.37E-17 1.078 4.91E-13
2897 ILMN .2370907 5892 RAD51L3 -0.653 8.76E-08 0.637 1.51E-07
2898 ILMN .2372082 6638 SNRPN -0.493 7.20E-08 0.453 5.65E-07
2899 ILMN .2372398 7915 ALDH5A1 -1.148 1.58E-13 0.508 2.71E-06
2900 ILMN .2373099 23318 ZCCHC11 -0.271 2.99E-03 0.429 7.54E-06
2901 ILMN .2374425 898 CCNE1 -0.659 5.40E-10 0.842 3.06E-12
2902 ILMN .2376194 816 CAMK2B -0.493 8.02E-06 0.481 1.09E-05
2903 ILMN .2376416 91544 UBXN11 -0.409 4.81E-06 0.308 3.14E-04 2904 ILMN_ ,2377240 64400 AKTIP -0.736 6.05E-11 0.229 3.63E-03
2905 ILMN_ ,2377900 4131 MAP IB -0.245 9.51E-03 0.965 5.76E-12
2906 ILMN_ .2379560 8555 CDC14B -0.331 1.77E-04 0.224 7.40E-03
2907 ILMN_ ,2381476 51062 SPG3A -0.748 3.05E-10 0.519 5.18E-07
2908 ILMN_ ,2382121 4952 OCRL -0.562 6.70E-07 0.297 2.00E-03
2909 ILMN_ ,2382829 7001 PRDX2 -0.990 4.03E-14 0.470 4.83E-07
2910 ILMN_ ,2383975 25824 PRDX5 -0.683 1.72E-09 0.371 5.70E-05
2911 ILMN_ ,2384807 85444 LRRCC1 -0.917 2.08E-12 0.330 1.35E-04
2912 ILMN_ ,2385688 11158 RABL2B -0.354 2.24E-04 0.500 2.10E-06
2913 ILMN_ ,2386016 51374 C2orf28 -0.538 3.31E-08 0.255 1.50E-03
2914 ILMN_ ,2386530 6176 RPLP1 -0.226 2.00E-03 0.307 1.29E-04
2915 ILMN_ ,2386982 5590 PRKCZ -1.063 4.50E-12 0.297 3.33E-03
2916 ILMN_ ,2387952 54463 FAM134B -0.219 9.71E-03 0.940 1.45E-12
2917 ILMN_ ,2390338 10477 UBE2E3 -0.843 1.27E-11 0.225 7.52E-03
2918 ILMN_ ,2390416 7917 BAT3 -0.257 2.98E-03 0.405 1.81E-05
2919 ILMN_ ,2392189 10217 CTDSPL -1.263 3.72E-17 1.064 5.12E-15
2920 ILMN_ ,2393994 79848 CSPP1 -0.869 5.70E-11 0.447 1.59E-05
2921 ILMN_ ,2397347 6406 SEMG1 -1.542 1.47E-17 0.318 5.13E-04
2922 ILMN_ ,2400292 5601 MAPK9 -0.566 6.77E-07 0.593 3.43E-07
2923 ILMN_ ,2400352 55367 LRDD -1.376 3.81E-17 0.640 2.94E-09
2924 ILMN_ ,2400922 4987 OPRL1 -1.003 7.46E-14 0.735 1.48E-10
2925 ILMN_ ,2401436 9088 PKMYT1 -0.778 3.27E-09 0.490 6.03E-06
2926 ILMN_ ,2401779 399665 FAM102A -0.409 5.44E-05 0.623 6.86E-08
2927 ILMN_ ,2404906 151648 SGOL1 -0.235 9.45E-03 0.309 1.03E-03
2928 ILMN_ ,2406468 27247 NFU1 -0.239 5.45E-03 0.383 5.75E-05
2929 ILMN_ ,2407124 84515 MCM8 -0.601 9.16E-06 0.724 3.72E-07
2930 ILMN_ ,2409298 51203 NUSAP1 -1.166 2.88E-15 0.378 3.12E-05
2931 ILMN_ ,2409318 91433 RCCD1 -1.341 1.28E-13 0.445 1.34E-04
2932 ILMN_ ,2410540 835 CASP2 -0.988 5.00E-14 0.456 9.39E-07
2933 ILMN_ ,2411190 10592 SMC2 -1.221 1.02E-14 0.584 8.76E-08
2934 ILMN_ ,2411781 6261 RYR1 -0.781 4.92E-09 0.364 5.33E-04
2935 ILMN_ ,2412384 9134 CCNE2 -0.835 2.90E-11 1.644 2.01E-18
2936 ILMN_ ,2413259 122809 SOCS4 -0.348 5.88E-04 0.265 6.16E-03
2937 ILMN_ ,2413650 6491 STIL -0.597 2.17E-08 0.394 1.91E-05
2938 ILMN_ ,2413898 55388 MCM10 -1.035 2.41E-13 0.561 1.08E-07
2939 ILMN_ 2414014 8241 RBM10 -0.340 8.43E-05 0.447 1.96E-06
2940 ILMN_ ,2414826 23230 VPS13A -0.684 3.06E-08 0.423 7.56E-05
2941 ILMN_ ,2415529 55755 CDK5RAP2 -0.554 7.59E-07 0.390 9.93E-05
2942 ILMN_ ,2415776 51741 wwox -0.502 4.27E-07 0.375 3.59E-05
2943 ILMN_ ,2415911 10495 ENOX2 -0.229 9.34E-03 0.237 8.01E-03
2944 ILMN_ ,3177532 100130717 CECR4 -0.295 7.53E-04 0.240 4.68E-03
2945 ILMN_ ,3179620 100129673 LOCI 00129673 -0.637 1.72E-08 0.484 2.73E-06
2946 ILMN_ ,3180557 284613 CYB561D1 -0.206 9.77E-03 0.302 2.71E-04
2947 ILMN_ ,3181695 100130178 LOC100130178 -0.664 4.13E-09 0.229 7.24E-03 2948 ILMN_ ,3185144 100128975 LOCI 00128975 -0.218 8.02E-03 0.262 1.83E-03
2949 ILMN_ ,3187771 55449 C14orfl67 -0.589 3.24E-09 0.316 9.16E-05
2950 ILMN_ .3189585 379025 FLJ31306 -0.375 1.23E-04 0.372 1.28E-04
2951 ILMN_ .3190486 253650 ANKRD18A -0.732 3.42E-08 0.347 5.48E-04
2952 ILMN_ ,3194087 29092 HSPC157 -0.711 7.50E-10 0.323 2.98E-04
2953 ILMN_ .3199647 645251 LOC645251 -0.542 6.11E-07 0.373 1.65E-04
2954 ILMN_ .3206064 646674 LOC646674 -0.503 2.63E-05 0.601 2.00E-06
2955 ILMN_ .3208995 653075 LOC653075 -0.469 3.88E-04 0.566 2.39E-05
2956 ILMN_ .3214625 644353 LOC644353 -0.286 5.11E-03 0.362 6.58E-04
2957 ILMN_ .3217276 644517 LOC644517 -0.281 4.52E-03 0.559 1.06E-06
2958 ILMN_ .3220769 729964 LOC729964 -0.498 1.49E-06 0.221 6.51E-03
2959 ILMN_ .3222425 729852 LOC729852 -0.315 4.23E-04 0.353 1.34E-04
2960 ILMN_ .3224126 729222 LOC729222 -0.503 1.86E-05 0.461 1.32E-05
2961 ILMN_ .3225406 728640 LOC728640 -0.215 5.55E-03 0.275 5.71E-04
2962 ILMN_ .3227023 84973 SNHG7 -0.470 5.03E-06 0.474 5.42E-06
2963 ILMN_ .3228585 728661 LOC728661 -0.651 6.62E-09 0.274 2.16E-03
2964 ILMN_ .3230880 222389 BEND7 -0.478 2.23E-05 0.578 2.82E-07
2965 ILMN_ .3234993 140823 ROMOl -0.222 6.57E-03 0.223 7.58E-03
2966 ILMN_ .3235104 85459 KIAA1731 -0.298 9.72E-04 0.531 5.14E-07
2967 ILMN_ .3235279 55698 RADIL -0.434 1.19E-05 0.484 7.44E-07
2968 ILMN_ .3235808 100101267 POM121C -0.365 1.67E-05 0.205 8.58E-03
2969 ILMN_ .3235922 29125 Cl lorOl -0.698 9.33E-09 0.338 5.61E-04
2970 ILMN_ .3236021 100133923 LOC100133923 -1.409 1.12E-15 0.370 1.38E-04
2971 ILMN_ .3236239 100129550 LOCI 00129550 -0.744 2.16E-10 0.459 1.38E-06
2972 ILMN_ .3236556 137886 UBXN2B -0.467 2.12E-06 0.404 1.51E-05
2973 ILMN_ .3236680 100134393 LOCI 00134393 -0.268 7.00E-04 0.231 3.23E-03
2974 ILMN_ .3236713 23642 SNHG1 -0.306 3.04E-03 0.625 4.98E-08
2975 ILMN_ .3236756 80221 ACSF2 -0.528 1.19E-07 0.644 1.54E-09
2976 ILMN_ .3237270 100133609 LOC100133609 -0.483 6.50E-07 0.670 3.35E-10
2977 ILMN_ .3237679 375743 PTAR1 -0.544 3.02E-08 0.250 1.32E-03
2978 ILMN_ .3237755 23145 SSPO -0.382 1.76E-04 0.315 9.97E-04
2979 ILMN_ .3237884 285548 LOC285548 -0.348 7.83E-04 0.573 1.24E-06
2980 ILMN_ .3237991 645166 LOC645166 -0.383 5.31E-05 0.573 6.22E-08
2981 ILMN_ .3238058 151162 LOC151162 -0.241 3.31E-03 0.572 3.53E-08
2982 ILMN_ .3238269 4700 NDUFA6 -0.247 5.10E-03 0.338 2.43E-04
2983 ILMN_ .3238326 9781 RNF144A -0.954 3.68E-13 0.616 8.16E-09
2984 ILMN_ .3238623 90624 LYRM7 -0.929 8.34E-12 0.610 3.97E-08
2985 ILMN_ .3238889 23248 RPRD2 -0.612 2.18E-08 0.247 4.83E-03
2986 ILMN_ .3239263 644128 RPL23AP53 -0.601 4.82E-09 0.487 2.94E-07
2987 ILMN_ .3239435 3064 HTT -0.586 8.40E-07 0.251 8.90E-03
2988 ILMN_ .3239861 387640 C10orfl40 -1.377 1.10E-14 0.504 8.99E-06
2989 ILMN_ .3239922 146771 TCAM1 -0.862 5.18E-12 0.246 2.92E-03
2990 ILMN_ .3240524 54842 MFSD6 -0.243 4.31E-03 0.352 6.71E-05
2991 ILMN_ .3240698 388279 LOC388279 -0.613 1.48E-06 0.403 3.16E-05 2992 ILMN_ ,3240740 51386 EIF3L -0.562 5.51E-09 0.300 1.92E-04
2993 ILMN_ ,3241046 4603 MYBL1 -0.725 6.87E-09 1.128 7.61E-14
2994 ILMN_ ,3241091 100130886 LOCI 00130886 -0.484 6.51E-07 0.337 1.32E-04
2995 ILMN_ ,3241257 55718 POLR3E -0.300 5.52E-04 0.269 2.02E-03
2996 ILMN_ ,3241262 132430 PABPC4L -0.491 7.22E-06 0.392 1.67E-04
2997 ILMN_ ,3241510 200933 FBX045 -0.580 5.15E-07 0.324 1.25E-03
2998 ILMN_ ,3242253 653501 LOC653501 -0.311 2.70E-04 0.220 5.21E-03
2999 ILMN_ ,3242586 58480 RHOU -0.797 4.70E-10 0.322 4.41E-04
3000 ILMN_ ,3243324 401491 FLJ35024 -1.284 3.70E-15 1.616 5.29E-18
3001 ILMN_ ,3243664 440353 LOC440353 -0.560 5.65E-05 0.599 1.81E-05
3002 ILMN_ ,3243899 286144 C8orf83 -0.639 1.98E-08 0.271 2.87E-03
3003 ILMN_ ,3243945 440145 C13orf37 -0.460 2.91E-06 0.242 3.49E-03
3004 ILMN_ ,3243982 116841 SNAP47 -0.297 2.96E-04 0.266 1.20E-03
3005 ILMN_ ,3244065 90120 C9orf69 -0.785 9.43E-12 0.301 2.73E-04
3006 ILMN_ ,3244248 645203 TMEM14D -0.700 6.06E-09 0.571 2.10E-07
3007 ILMN_ ,3244286 26115 TANC2 -0.377 2.21E-05 0.620 4.43E-09
3008 ILMN_ 3244314 100132048 LOCI 00132048 -0.289 2.77E-03 0.256 5.50E-03
3009 ILMN_ ,3244323 148413 LOCI 48413 -0.479 6.41E-07 0.537 1.30E-07
3010 ILMN_ ,3244982 100133099 LOC100133099 -0.394 7.31E-05 0.244 8.55E-03
3011 ILMN_ ,3245351 84747 UNC119B -0.430 5.82E-05 0.276 4.16E-03
3012 ILMN_ ,3245410 196872 MGC23270 -0.243 1.27E-02 0.280 4.08E-03
3013 ILMN_ ,3245559 8099 CDK2AP1 -0.317 1.77E-04 0.228 4.68E-03
3014 ILMN_ ,3245659 90459 ERI1 -0.872 1.64E-11 0.232 7.76E-03
3015 ILMN_ ,3245688 85359 DGCR6L -0.272 1.31E-03 0.771 9.58E-11
3016 ILMN_ ,3245849 399967 PATE2 -0.420 2.48E-04 0.294 3.93E-03
3017 ILMN_ ,3245983 54492 NEURL1B -0.396 2.66E-05 0.579 7.51E-08
3018 ILMN_ ,3246962 23384 CYTSA -0.272 7.21E-04 0.351 4.89E-05
3019 ILMN_ ,3247504 23354 HAUS5 -0.499 1.36E-05 0.300 2.32E-03
3020 ILMN_ ,3247681 388969 C2orf68 -0.789 4.54E-11 0.229 6.43E-03
3021 ILMN_ ,3247802 84726 BAT2L -0.343 1.80E-03 0.383 3.06E-04
3022 ILMN_ ,3247857 100132345 LOCI 00132345 -0.693 1.06E-09 0.750 1.96E-10
3023 ILMN_ ,3248301 147949 ZNF583 -0.397 1.14E-05 0.320 2.10E-04
3024 ILMN_ 3248443 641638 SNHG6 -0.693 6.65E-10 0.253 2.15E-03
3025 ILMN_ ,3248906 55906 ZC4H2 -0.604 6.63E-09 0.591 1.32E-08
3026 ILMN_ ,3249261 100132299 LOCI 00132299 -1.042 9.30E-12 0.282 5.43E-03
3027 ILMN_ ,3249281 221883 HOXA11AS -0.584 4.24E-08 0.541 2.52E-07
3028 ILMN_ ,3249682 256126 SYCE2 -0.455 6.01E-05 0.411 9.70E-05
3029 ILMN_ ,3249807 348235 SKA2 -1.217 9.47E-16 0.487 6.73E-07
3030 ILMN_ ,3251404 64710 NUCKS1 -0.785 4.47E-10 0.353 5.19E-05
3031 ILMN_ ,3251482 144245 ALG10B -0.826 1.92E-10 0.413 4.59E-05
3032 ILMN_ ,3251672 1829 DSG2 -1.290 2.64E-16 0.714 3.33E-10
3033 ILMN_ ,3253126 650669 FLJ41484 -0.345 1.58E-03 0.411 1.40E-04
3034 ILMN_ ,3254984 100129759 LOCI 00129759 -0.613 4.48E-08 0.270 1.75E-03
3035 ILMN_ ,3256801 84852 Clorf203 -0.387 4.67E-05 0.782 1.47E-10 3036 ILMN_ .3262193 729634 KRT18P26 -0.347 5.79E-04 0.250 6.51E-03
3037 ILMN_ .3265237 645460 FLJ44342 -0.657 3.27E-08 0.281 3.36E-03
3038 ILMN_ .3265365 84131 CEP78 -1.170 2.52E-14 0.379 8.76E-05
3039 ILMN_ .3270411 100129890 LOCI 00129890 -0.366 8.39E-05 0.356 9.37E-05
3040 ILMN_ .3272500 122509 IFI27L1 -0.261 1.55E-03 0.465 1.34E-06
3041 ILMN_ .3275590 647302 LOC647302 -0.687 4.75E-10 0.353 5.67E-05
3042 ILMN_ .3277402 441242 LOC441242 -0.981 7.51E-13 0.532 2.75E-07
3043 ILMN_ .3279449 728052 LOC728052 -0.267 2.13E-03 0.446 2.11E-06
3044 ILMN_ .3281563 648771 LOC648771 -0.235 4.94E-03 0.220 7.04E-03
3045 ILMN_ .3282983 100132992 LOCI 00132992 -0.403 8.19E-05 0.427 4.68E-05
3046 ILMN_ .3288755 646808 LOC646808 -0.611 1.71E-07 0.426 3.00E-05
3047 ILMN_ .3289346 442075 LOC442075 -0.780 4.45E-09 0.512 1.62E-06
3048 ILMN_ .3293367 391370 LOC391370 -0.317 4.72E-04 0.262 3.22E-03
3049 ILMN_ .3298400 731954 LOC731954 -0.511 5.98E-06 0.373 1.56E-04
3050 ILMN_ .3298511 728537 LOC728537 -0.411 3.66E-05 0.672 1.33E-08
3051 ILMN_ .3300313 54681 P4HTM -0.920 2.32E-13 0.828 3.04E-12
3052 ILMN_ .3301042 642946 LQK1 -0.220 9.89E-03 0.634 1.75E-08
3053 ILMN_ .3301749 124976 SPNS2 -0.314 1.64E-03 0.245 5.83E-03
3054 ILMN_ .3303612 80336 PABPC1L -0.519 5.80E-06 0.607 4.65E-07
3055 ILMN_ .3305273 729779 LOC729779 -0.840 2.73E-10 1.786 2.77E-18
3056 ILMN_ .3305304 5425 POLD2 -1.114 8.54E-14 0.398 3.90E-05
3057 ILMN_ .3307266 29893 PSMC3IP -0.400 1.76E-05 0.897 3.02E-12
3058 ILMN_ .3307683 57116 ZNF695 -0.419 8.40E-06 0.429 8.37E-06
3059 ILMN_ .3307782 80028 FBXL18 -0.841 5.28E-11 0.429 1.63E-05
3060 ILMN_ .3307827 3338 DNAJC4 -0.380 1.05E-04 0.341 4.24E-04
3061 ILMN_ .3309349 100093630 SNHG8 -0.328 3.30E-04 0.565 1.47E-07
3062 ILMN_ .3310491 100302173 MIR1978 -0.218 3.81E-03 0.345 2.98E-05
[0085] Table 4. Enrichment of significant Gene Ontologies in differentially regulated 3062 genes between resveratrol (RES) treated Mycobacterium tuberculosis infected THP-1 cells (R) vs untreated Mycobacterium tuberculosis infected THP-1 cells (I).
Observed Expected
Description of Gene ontology Number of Number of P value
genes genes
DNA strand elongation involved in DNA
24 5.17 5.90E-13 replication
telomere maintenance via semi-
17 3.65 1.40E-09 conservative replication
telomere maintenance via recombination 17 3.96 9.40E-09 inflammatory response 149 85.98 2.80E-07
Gl/S transition of mitotic cell cycle 74 36.52 7.00E-07 mitotic cell cycle 214 136.5 2.50E-06 nucleotide -excision repair, DNA gap
12 2.89 2.70E-06 filling
interferon-gamma-mediated signaling 29 11.41 6.70E-06 pathway
9 interleukin- 10 secretion 8 1.52 9.60E-06
,„ regulation of MHC class I biosynthetic ,„ „ , ,„„ nc
10 12 3.2 1.10E-05 process
, , macrophage activation involved in n , nn , nc
11 . r ° 9 1.98 1.70E-05 immune response
12 positive regulation of phagocytosis 16 5.33 1.80E-05
13 mismatch repair 13 3.8 1.90E-05
14 DNA replication initiation 14 4.57 4.50E-05
15 T cell costimulation 24 10.5 4.60E-05
16 fatty acid beta-oxidation 20 8.98 5.40E-05
Figure imgf000113_0001
pro uction
18 phagosome maturation 18 7 6.90E-05
19 interaction with host 37 17.65 8.50E-05
20 defense response to virus 52 30.74 9.80E-05
21 cellular response to lipopolysaccharide 40 17.5 1.00E-04
22 regulation of transcription involved in ^ g g 1 10E 04 Gl/S transition of mitotic cell cycle
22 intrinsic apoptotic signaling pathway in ^ 16 28 1 30E 04 response to DNA damage
24 regulation of cell shape 32 16.74 1.50E-04
25 positive regulation of apoptotic process 85 58.59 1.60E-04
26 regulation of interleukin- 10 production 15 5.78 1.60E-04
27 double-strand break repair via 24 10.65 1.70E-04 homologous recombination
28 negative regulation of T cell proliferation 17 6.85 1.80E-04
29 regulation of interferon-beta production 13 5.33 1.80E-04
30 toll -like receptor 4 signaling pathway 33 16.28 2.00E-04
31 Fc-gamma receptor signaling pathway 23 10 8 2 20E-04 involved in phagocytosis
32 regulation of cell proliferation 251 202.69 2.40E-04 humoral immune response mediated by „ „.
33 , . , , ,· 16 7.15 2.60E-04 circulating immunoglobulin
^ modification by symbiont of host ^ ^ 72 2 60E 04 morphology or physiology
35 DNA replication 88 46.11 2.90E-04
36 dicarboxylic acid biosynthetic process 7 1.67 3.50E-04
37 regulation of cytokine secretion 35 16.13 3.50E-04
38 response to peptidoglycan 7 1.67 3.50E-04
39 cell proliferation 346 266 4.00E-04
40 negative regulation of NF-kappaB 21 9 89 4 30E-04 transcription factor activity
41 base-excision repair 16 6.7 4.60E-04
42 response to exogenous dsRNA 15 6.09 4.70E-04
43 MyD88-dependent toll-like receptor 25 12 7g 5 20E 04 signaling pathway
44 negative regulation of lymphocyte 3? 15 6? 5 20E-04 activation
antigen processing and presentation of
45 exogenous peptide antigen via MHC 21 12.02 5.30E-04 class I 46 cytokine -mediated signaling pathway 110 59.2 5.30E-04
47 response to interleukin-1 26 11.11 5.40E-04
A O positive regulation of release of 1 t 0 c C .
48 , „ , , . 11 3.o 5.50E-04 cytochrome c from mitochondria
49 mitochondrial transport 38 25.87 6.30E-04
50 positive regulation of cytokine secretion 22 10.35 6.40E-04
51 toll-like receptor signaling pathway 50 21.76 6.50E-04
52 oxidation-reduction process 190 152.63 6.80E-04
53 regulation of protein kinase activity 130 104.09 6.80E-04
54 respiratory burst 8 3.96 6.80E-04
55 positive regulation of catalytic activity 252 200.26 7.20E-04
56 microglial cell activation 7 1.83 7.30E-04
57 cell surface receptor signaling pathway 489 483.76 7.70E-04
58 mitotic nuclear division 81 56.46 7.70E-04
59 toll-like receptor 2 signaling pathway 23 11.72 8.10E-04
60 embryo implantation 15 6.39 8.60E-04
61 positive regulation of angiogenesis 28 15.37 8.80E-04
62 dendritic cell differentiation 13 5.48 9.30E-04
63 actin cytoskeleton organization 98 73.5 1.02E-03
64 regulation of type 2 immune response 10 3.5 1.11E-03
65 2-oxoglutarate metabolic process 8 2.43 1.16E-03
66 defense response to protozoan 8 2.43 1.16E-03 ,„ positive regulation of I-kappaB o o l o c na kmase/NF-kappaB signaling
„ regulation of myeloid leukocyte mediated ,„ „ , „
68 . . J J 10 3.65 1.30E-03 immunity
69 mitotic chromosome condensation 7 1.98 1.38E-03 positive regulation of immunoglobulin
/0 ,. , . / 1.9o 1.3oE-03 mediated immune response
71 T-helper 2 cell differentiation 7 1.98 1.38E-03 nr. regulation of cyclin -dependent protein n
senne/threonme kinase activity
73 positive regulation of peptidase activity 35 21 1.46E-03
74 biotin metabolic process 6 1.52 1.49E-03
75 kynurenine metabolic process 6 1.52 1.49E-03 negative regulation of transcription by , , co . ,n m
/6 . . . . ,. 6 l .jZ 1.4yE-03 competitive promoter binding
77 lipopolysaccharide -mediated signaling ^ ^ ^ 7QE ^ pathway
78 extracellular matrix disassembly 32 19.02 1.71E-03
79 histone phosphorylation 11 4.26 1.72E-03
80 response to progesterone 12 4.87 1.73E-03
81 negative regulation of leukocyte 45 J g % 1 79E-03 activation
g2 negative regulation of peptidyl-tyrosine ^ 4 g? 1 89E-03 phosphorylation
positive regulation of insulin secretion
83 involved in cellular response to glucose 8 2.59 1.90E-03 stimulus
84 tetrahydrofolate metabolic process 8 2.59 1.90E-03
„. negative regulation of innate immune n 0 0 00 o5 9 3.2 . E-03 response
86 protein folding 46 31.96 2.25E-03 87 regulation of lipid kinase activity 15 6.24 2.33E-03
88 cellular response to ionizing radiation 14 7.15 2.34E-03
89 regulation of T cell mediated cytotoxicity 8 3.8 2.35E-03 glutamine family amino acid catabolic
90 10 3.8 2.37E-03 process
positive regulation of toll-like receptor
91 7 2.13 2.39E-03 signaling pathway
antigen processing and presentation of
92 exogenous peptide antigen via MHC 25 14.15 2.57E-03 class II
93 response to virus 77 45.5 2.67E-03 immunoglobulin production involved in
94 immunoglobulin mediated immune 15 7.3 2.83E-03 response
95 T-helper 1 type immune response 13 5.78 2.84E-03
96 hepatocyte differentiation 6 1.67 2.86E-03
97 L-ascorbic acid metabolic process 6 1.67 2.86E-03
98 phospholipid efflux 6 1.67 2.86E-03 positive regulation of humoral immune
99 6 1.67 2.86E-03 response
positive regulation of nitric -oxide
100 6 1.67 2.86E-03 synthase biosynthetic process
101 translesion synthesis 6 1.67 2.86E-03 negative regulation of type I interferon
102 13 5.78 2.92E-03 production
103 cytoplasmic transport 135 129.96 2.95E-03
104 detection of bacterium 8 2.74 2.97E-03 nucleotide -binding domain, leucine rich
105 repeat containing receptor signaling 12 7.76 2.98E-03 pathway
106 granulocyte chemotaxis 23 11.11 2.99E-03
107 regulation of DNA repair 18 8.52 3.01E-03
108 response to lipopolysaccharide 69 35 3.02E-03
109 leukocyte cell-cell adhesion 14 7.76 3.25E-03 toll-like receptor TLR1 :TLR2 signaling
110 20 10.8 3.71E-03 pathway
toll-like receptor TLR6:TLR2 signaling
111 20 10.8 3.71E-03 pathway
positive regulation of interleukin-6
112 13 5.93 3.78E-03 production
aspartate family amino acid catabolic
113 7 2.28 3.90E-03 process
114 DNA-dependent DNA replication 52 19.33 4.22E-03
115 cellular response to mechanical stimulus 19 10.2 4.26E-03
116 apoptotic cell clearance 13 4.41 4.41E-03
117 cell recognition 21 17.04 4.46E-03
118 extrinsic apoptotic signaling pathway 52 33.48 4.46E-03
119 B cell receptor signaling pathway 16 5.93 4.52E-03
120 collagen catabolic process 21 11.72 4.54E-03
121 regulation of cell cycle 164 124.02 4.61E-03
122 response to toxic substance 35 21.15 4.61E-03
123 middle ear morphogenesis 9 3.5 4.63E-03 124 positive regulation vascular endothelial ^
3.5 4.63E-03 growth factor production
125 response to ATP 9 3.5 4.63E-03
126 cell-cell adhesion mediated by integrin 6 1.83 4.98E-03 negative regulation of interleukin-12 ^
127 1.83 4.98E-03 production
regulation of B cell receptor signaling
128 1.83 4.98E-03 pathway
129 response to host immune response 6 1.83 4.98E-03
130 response to hydroperoxide 6 1.83 4.98E-03
131 neural precursor cell proliferation 17 19.17 5.05E-03 substrate adhesion-dependent cell ^
9.89 5.31E-03 spreading
j 22 positive regulation of tumor necrosis ^
5.48 5.32E-03 factor production
134 signal transduction 847 795.41 5.37E-03
135 carbohydrate derivative catabolic process 237 187.63 5.73E-03
136 cell cycle checkpoint 59 37.59 6.02E-03 j 2γ positive regulation of cell adhesion ^
2.43 6.03E-03 mediated by integrin
138 regulation of cellular senescence 7 2.43 6.03E-03
139 endodermal cell differentiation 12 6.7 6.18E-03
140 glutamine metabolic process 9 3.65 6.43E-03
141 negative regulation of autophagy 9 3.65 6.43E-03 positive regulation of acute inflammatory ^
142 3.65 6.43E-03 response
143 phagocytosis, engulfment 8 3.04 6.44E-03
144 response to unfolded protein 28 20.09 6.75E-03
145 cellular lipid metabolic process 168 135.43 7.36E-03
146 positive regulation of phospholipase ^
11.87 8.05E-03 activity
cytoskeletal anchoring at plasma ^
1.98 8.07E-03 membrane
148 eosinophil migration 6 1.98 8.07E-03
149 negative regulation of cell division 6 1.98 8.07E-03 positive regulation of antigen receptor- ^
1.98 8.07E-03 mediated signaling pathway
positive regulation of fatty acid ^
1.98 8.07E-03 biosynthetic process
152 replication fork processing 6 1.98 8.07E-03 ^2 negative regulation of inflammatory
12.93 8.23E-03 response
transcription-coupled nucleotide -excision ^
7.15 8.32E-03 repair
155 neutrophil chemotaxis 16 8.98 8.57E-03 regulation of type I interferon-mediated ^
5.78 8.59E-03 signaling pathway
positive regulation of inflammatory ^
11.87 8.68E-03 response
158 cellular response to interleukin-4 9 3.8 8.71E-03
159 centriole replication 7 2.59 8.93E-03
160 epithelial cell fate commitment 7 2.59 8.93E-03
161 glycine metabolic process 7 2.59 8.93E-03 162 plasma lipoprotein particle assembly 7 2.59 8.93E-03
163 double-strand break repair 42 20.54 8.99E-03
164 G2 DNA damage checkpoint 12 5.48 9.00E-03 negative regulation of toll-like receptor
165 8 3.2 9.03E-03 signaling pathway
166 ATP catabolic process 71 53.41 9.36E-03
167 chemokine-mediated signaling pathway 13 6.54 9.47E-03
168 cellular component organization 893 747.62 9.64E-03
[0086] Table 5. Enrichment of significant canonical pathways (IPA analysis) in differentially regulated genes between resveratrol (RES) treated Mycobacterium tuberculosis infected THP-1 cells (R) vs untreated Mycobacterium tuberculosis infected THP-1 cells (I).
Ingenuity Canonical -log(p-
Ratio Molecules
Pathways value)
Mismatch Repair in 7.63E00 7.5E- PCNA,MSH2,RFC4,MSH6,RFC2, FEN1, Eukaryotes 01 RFC1,RPA1,RFC5,MLH1, EX01,RFC3
TREM1 Signaling 6.51E00 3.6E- LAT2,TLR8,CIITA,IL6,JAK2, FCGR2B,
01 IRAKI, CCL2,MAPK3, TLR1,TLR7, CASP1, TLR3,GRB2,MYD88,TYROBP, ITGA5, PLCG1,STAT3,TLR2,NLRC5, NOD2, NLRP12,TLR6,CD86, IL1B, CCL7
Cell Cycle Control of 5.87E00 5.19E- MCM6,CDC45,CDT1,CDC6, CDC7, CDK6, Chromosomal 01 0RC6,RPA1,MCM4,RPA2, MCM3,
Replication RPA3,CDK2, MCM7
Crosstalk between 5.38E00 3.15E- IL15RA,HLA-A,TNFSF10, IL6,
Dendritic Cells and 01 HLA-G,C AMK2D, HLA-DRB 1 ,
Natural Killer Cells HLA-DRB 3, HLA-DRA,
TLR7,LTBR, TLR3, TNFRSF1B,
CAMK2B,CD209, IL3RA,
TYROBP, CD69, CSF2RB,
TLN2, HLA-DRB4, CD80, HLA-C,
CD86, IFNA21, HLA-DRB5, CCR7,
PVRL2
Dendritic Cell 5.3E00 2.54E- ILIA, HLA-A, NFKBIE, HLA-DQA1, Maturation 01 PIK3R5, MAPK13, JAK2, IL6,
FCGR2B, FCGR1A, 1KB KB,
PLCD3, HLA-DRB 1, HLA-DMA, MAPK3, HLA-DRB 3, HLA-DRA,
PLCB 1,TLR3,
LTBR, PIK3R2, STAT1, TNFRSF1B,
FCGR1 B ,MYD88,FCGR2A, TNFRSF1A, TYROBP, MAPK9, PLCG1, IKBKE, TLR2, STAT4,HLA-DRB4, CD80, HLA-C,
IL1RN, MAPK10, FCER1G, CD86, HLA-DOB, IL1B, IFNA21, CCR7, HLA-DRB 5 T Helper Cell 5.3E00 3.38E- STAT6JL4R, TNFRSFIA, IL12RB 1, IFNGR2, Differentiation 01 HLA-DQA1,IL12RB2,IL6, STAT3,
BCL6, STAT4,HLA-DRB 1 , CD80,
HLA-DMA, HLA-DRAJLIORA, IL10RB, FCER1G,CD86, HLA-DOB, STAT1,
TNFRSFIB, ICOSLG/LOC 102723996, HLA-DRB5
Antigen Presentation 5.29E00 4.32E- HLA-A,HLA-DQA1,CIITA,PSMB8,
Pathway 01 TAP 1 ,HLA-G,NLRC5 , HLA-DRB 1,
HLA-DRB4, HLA-DMA,
HLA-CHLA-DRB3, HLA-DRA,
HLA-DOB, HLA-DRB5, HLA-DPA1
Aryl Hydrocarbon 5.29E00 2.71E- ALDH4A 1 ,IL 1 A,NFIX,POLA 1 ,IL6,
Receptor Signaling 01 RB L 1 ,CCND 1 ,TGM2, CTSD, RBI,
HSP90B1,NCOA7, ALDH1A1, GSTM2,
HSP90AB1,NCOA2, MAPK3, ALDH3A2, ALDH5A1, ALDH6A1, ALDH7A1, SRC, CCNE2,NFIC,TFDP1, GSTA4, CDK6, BAX, GST01,CYP1B1,AHRR,CCNE1, ILIB, DHFR, RXRA,ALDH 16A1 ,CDK2,MCM7
Hepatic Fibrosis / 4.9E00 2.46E- IGFBP4,MYH10,COL8A2,IL1A, CTGF,
Hepatic Stellate Cell 01 COL4A5,
Activation PDGFA, KLF6, MMP13, CCL5, IL6,
CXCL9, COL15A1, BCL2, IL1R2, COL6A1, CCL2, STAT1, TNFRSFIB, ΜΜΡ1/ΠΜΡ2, VCAM1, IL4R, EDNRB, COL6A2,
TNFRSF 1 A,FGFR 1 , COL12A1,
IFNGR2,IGFBP5,MMP2, MYH7,
BAXJFNAR2, IL18RAP,
MET,LY96,IGFBP3, IL10RA,
CD14,IL1B,PDGFD, A2M, MMP9, CCR7
Communication between 4.88E00 3.03E- IL1A,HLA-A,TLR8,IL6,CCL5,
Innate and Adaptive 01 HLA-G,HLA-DRB 1,CCL3L3,
Immune Cells HLA-DRB 3 ,TLR 1 ,HLA-DRA,
TLR7,TLR3,TNFSF13B,TLR2,
CCL4,HLA-DRB4,CD80,HLA-C,
IL1RN,TLR6,FCER1G,CD86,IL1B,
IFNA21,HLA-DRB5,CCR7
Role of BRCA1 in DNA 4.52E00 3.08E- FANCG,UIMC1,RPA1,RFC1,
Damage Response 01 MRE 11 A,RB L 1 ,RFC5 ,MLH 1 ,
FANCE,RB 1 ,FANCB,MSH2,
RFC4,GADD45A,MSH6,E2F5,
RFC2,STAT1,BLM,BRCA1,
HLTF,BRE,E2F2,RFC3
dTMP De Novo 4.44E00 1E00 TYMS,SHMT 1 ,DHFRL1 ,
Biosynthesis DHFR, SHMT2
Type I Diabetes Mellitus 4.36E00 2.73E- HLA-A,NFKBIE,HLA-DQA1,
Signaling 01 JAK2,MAPK13,IRAK1,BCL2,
HLA-GJKB KB ,HLA-DRB 1 ,
HLA-DMA,HLA-DRA,BID,
ST ATI, TNFRSF IB, TNFRSFIA,
MYD88,IFNGR2,MAPK9,IKB KE,
SOCS4,CD80,HLA-C,MAPK10,
FCER 1 G,HLA-DOB ,CD86,IL 1 B ,
CPE,HLA-DRB5 Estrogen-mediated S- 4.09E00 4.58E- RB 1 ,CCNE2,CCNE 1 ,TFDP 1 , phase Entry 01 E2F5,RBL1 ,CCND 1 ,E2F2,
CDK2,SKP2,CDC25A
Role of Pattern 4.02E00 2.56E- IL1A,IFNW1,PIK3R5,TLR8, Recognition Receptors in 01 C1QC,CCL5,C1QB,IL6,
Recognition of Bacteria IFN A 14,PRKCZ,M APK3 , and Viruses TLRl ,C ASP 1 ,TLR7,OSM,
TLR3,PIK3R2,C3,C5AR1,
MYD88,MAPK9,C5,TLR2,
NOD2,CLEC7A,PRKCI,
TLR6,MAPK10,IL1B,
IFNA21 ,C3 AR 1 ,PRKCB
Granulocyte Adhesion 3.9E00 2.32E- FPR3,IL1A,MMP7,CLDN15, and Diapedesis 01 MMP14,MMP15,MMP13,
CCL5,CXCL9,MMP25,
CCL4L1/CCL4L2, IL1R2,
HRH1,CCL13,CCL3L1,CXCL13,
CCL8, CCL2, CCL3L3, EZR,
CXCL1 ,TNFRSF1 B ,ΜΜΡ 1 ,
CXCL11,VCAM1,C5AR1,
TNFRSF1A,CKLF,
FPR2,ITGA5,MMP2,
IL18RAP,C5,ITGB2,
CCL4,ITGAM,IL1RN,
PEC AM 1 ,IL 1 B ,MMP9,CCL7
Role of Macrophages, 3.87E00 2.06E- TRAF3,FZD3,TLR8,MMP13, IL6, Fibroblasts and 01 FCGR1A,CCND1, CEBPGJL1R2, Endothelial Cells in PLCD3,IKBKB,CAMK2D, MAPK3, Rheumatoid Arthritis TLRl, PLCB l, OSM/TRAF5, LTBR,
TNFSF13B, STAT3, C5, TLR2,
ILIRN, FZD6, SFRPl, PDGFD, ILIA,
TCF4, SFRP2, PDGFA, NFKBIE,
P IK3R5,JAK2,CCL5,
IL17RA,PRKCZ,NFATC1,
IRAKI, CCL2,TLR7,TLR3,
PIK3R2,TNFRSF1 Β,ΜΜΡ 1 ,
CAMK2B,SRC,VCAM1,
C5AR1,MYD88, TNFRSFIA,
DAAM 1 ,MAPK9,PLCG 1 ,
1KB KE,IR AK3 ,IL 18RAP, PRKCI,
FZD4,TLR6,IL 1 B ,PRKCB
Small Cell Lung Cancer 3.76E00 TRAF3 ,CCNE2,TFDP 1 ,NFKB IE, Signaling 01 ABL1,CDK6,PIK3R5,IKBKE,
CCND1,SKP2,BCL2,IKBKB,
RB 1 ,CCNE 1 ,MAX,CKS 1 B ,
BID,PIK3R2,TRAF5,RXRA,CDK2
Graft- versus -Host 3.65E00 3.33E- IL1 A,HLA-A,HLA-DQA 1 ,IL6, Disease Signaling 01 HLA-G,HLA-DRB 1 ,CD80,
HLA-DMA,HLA-C,IL 1 RN,
HLA-DRA,FCER 1 G,
HLA-D0B,CD86,IL1B,HLA-DRB5
Fey Receptor-mediated 3.63E00 2.69E- VAV2,SRC,FCGR2A,
Phagocytosis in 01 ARPC5,PLCG1,CRK,
Macrophages and FYB ,FCGR1 AJNPP5D,
Monocytes PRKCZ,NCF1 ,ΡΑΚΙ ,CBL, TLN2,PRKCI,WAS,CDC42,
VAV3,ARPC2,EZR,MAPK3,
LYN,PIK3R2,LCP2,PRKCB LXR/RXR Activation SCD,APOE,ILlA,APOA4,
CD36,AP0C2,IL6,ABCA1,
IL 1 R2,CCL2,TLR3 ,TNFRSF1B ,
MLXIPL,AP0M,C3,TNFRSF1A,
NR1H3,IL18RAP,AP0L1, LY96,
LDLR, IL1RN,MYLIP, APOC1,
CD 14, IL1B,RXRA,HADH,MMP9,CCL7
IL-12 Signaling APOE,APOA4,IL12RB l, MAF, Production in PIK3R5,APOC2,MAPK13, IFNAIO, Macrophages IFNA14, PRKCZ, JMJD6,
IKBKB,MAPK3,IFNA7,
PIK3R2,STAT1,STAT6,AP0M,
MYD88,MAPK9,IL12RB2,
1KB KE,TLR2, APOL 1 ,IFN A 16,
STAT4,PRKCI,MAPK10, APOC 1 ,
IFNA21 ,RXRA,PRKCB
Production of Nitric APOE,APOA4,NFKBIE,PIK3R5, Oxide and Reactive APOC2,MAPK13,JAK2 , PRKCZ, Oxygen Species in IKBKB,PPP1R12A,PPP1R7,
Macrophages C YB A,MAPK3 ,ΗΟΧΑ 10,
RHOU,CYBB,PIK3R2,
STAT 1 ,TNFRSF 1 B , PTPN6,
APOM/TNFRSFl AJFNGR2,
M APK9,PLCG 1 ,1KB KE, NCF4,
PPP2R5 A,TLR2,APOLl ,NCF1 ,
PRKCI,PPP2R4,NCF2,CAT,
MAPK10, APOC 1 ,FNBP 1 ,
SIRPA,PRKCB
CD28 Signaling in T NFKB IE, ARPC5 ,PIK3R5 ,HLA-DQ A 1 , Helper Cells CTLA4,NFATC1,PTPRC,IKBKB,
PAK1 ,HLA-DRB 1 ,HLA-DMA,
HLA-DRA,PIK3R2,PTPN6,GRB2,
MAPK9,PLCG 1 ,1KB KE,CD80,
CDC42,WAS,ARPC2,ITPR3,
FCER1G,MAPK10,HLA-DOB,
CD86,LCP2,HLA-DRB5
Complement System ITGB2,CFD,SERPING1,ITGAM,
C3,C5AR1,CFB,C1QC,C1QB,
CFH,C3AR1,C2,C5
Glioma Signaling PDGFA,ABL1,PIK3R5,RBL1,
CCND 1 ,PRKCZ,IDH 1 ,RB 1 ,MTOR,
CAMK2D,MAPK3,E2F5,PIK3R2,
E2F2,CAMK2B,TFDP1,GRB2,CDK6,
PLCG1,IGF2R,CDKN2D,PRKCI,
IDH2,PDGFD,PRKCB NF-κΒ Signaling 3.23E00 2.21E IL 1 A,TRAF3 ,TGFB R3 ,NFKBIE,
01 PIK3R5,TLR8,BMPR2,PRKCZ,
IRAK1,FGFR3,IL1R2,IKBKB,
TNIP 1 ,UBE2V 1 ,TLR1,TLR7,
TDP2,TLR3 ,LTBR,TRAF5 ,
PIK3R2,TNFRSF1B,TNFSF13B,
MYD88,TNFRSF1A,FGFR1,TBK1,
IRAK3,IGF2R,TLR2,GHR,ARAF,
IL 1 RN,PELI 1 ,TLR6,FCER 1 G,
IL1B,PRKCB
Activation of IRF by 3.2E00 2.9E- DHX58,TRAF3,PPIB,NFKBIE,
Cytosolic Pattern 01 ZBP 1 ,MAPK9,TBK1 ,1KB KEJL6,
Recognition Receptors IFN A 1 OJFNA 14 FNA 16,1KB KB,
IFNA7,MAPK10 FNA21 ,ΡΙΝ 1 ,STAT 1
Altered T Cell and B 3.2E00 2.61E IL1A,TRAF3,SPP1,TLR8,HLA-DQA1, Cell Signaling in 01 IL6,TLR2,HLA-DRB 1 ,CXCL13,
Rheumatoid Arthritis CD80,HLA-DMA,IL1RN,HLA-DRA,
TLR 1 ,TLR6,TLR7,FCER 1 G,
HLA-D0B,CD86,IL1B,TLR3,
TNFSF13B,HLA-DRB5
Role of 3.15E00 3.26E CCR1,IL1A,CCL5 ,IL6,IFN A 10,
Hypercytokinemi a/hyper 01 IFN A 14,IFN A 16,CCL4,CCL2,
chemokinemia in the IL 1 RNJFN A7,IL 1 B JFNA21JFNL1 Pathogenesis of
Influenza
Leukocyte Extravasation 3.12E00 2.12E- MMP7,CLDN15,MMP14,MMP15,
Signaling 01 PIK3R5,ABL1,MMP13,CRK,
M APK13 ,MMP25 ,PRKCZ,
CYBA,EZR,CYBB,VCL,PIK3R2,
MMP1,TIMP2,VAV2,TIMP3,
SRC,VCAM1,MAPK9,ITGA5,
PLCG1,MMP2,NCF4,BTK,ITGB2,
NCF1 ,WIPF1 ,ITGAM,PRKCI,
RAP1GAP,WAS,CDC42,VAV3,
NCF2,MAPK10,PEC AM 1 ,MMP9,
PRKCB
Colorectal Cancer 3.05E00 2.03E- MMP7,TCF4,FZD3,MMP14,MMP15, Metastasis Signaling 01 TLR8,PIK3R5,MMP13,JAK2,IL6,
MMP25,CCND 1 ,MLH 1 ,GNG7,GNB4, GNG11,MAPK3,TLR1,RH0U,TLR7, TLR3 ,PIK3R2,GNG5 ,STAT 1 ,RALGDS , MMP1,SRC,GRB2,TNFRSF1A,ADCY3, MAPK9,MMP2,BAX,STAT3,GNG 10, TLR2,FZD4,MSH2,ADCY1,TLR6,MAPK10, MSH6,PRKAG2,FZD6,PTGER2,ADCY7, FNBP1,MMP9
Role of CHK Proteins in 2.92E00 2.91E- MRE11A,RFC1,RPA1,RFC5,
Cell Cycle Checkpoint 01 PPP2R5A,PCNA,RFC4,PPP2R4,
Control E2F5,RFC2,CLSPN,BRCA1,E2F2,
CDK2,RFC3,CDC25A phagosome maturation RAB5C,HLA-A,PRDX5,TCIRG1,
TAP1,NSF,HLA-DRB1,HLA-DRB3, HLA-DRA,CYBB,NAPA,M6PR,
ATP6V0E2, ATP6 V 1 C2, VPS 18,TUBG 1 , ATP6V 1 E2,VPS33 A,TUB A4A, ATP6V0A 1 , LAMP2,HLA-DRB4,HLA-C, ATP6V0D 1 , NCF2,ATP6V0E1,HLA-DRB5,PRDX2
Interferon Signaling IFIT1 ,PTPN2,MX1 ,IFNGR2,IFNA21 ,
PSMB8,BAX,JAK2,STAT1,IFNAR2, TAP1,BCL2
PI3K Signaling in B CD81 ,NFKBIE, ABL1 ,FCGR2B ,
Lymphocytes NFATC 1 ,PRKCZ,PTPRC,PLCD3,
IKBKB,CAMK2D,MAPK3,PLCB1,
PIK3R2,CAMK2B,VAV2,IL4R,C3,
PLCG 1 ,1KB KE,INPP5D,BTK,PRKCI,
CBL,DAPP1,VAV3,ITPR3,LYN,
PIK3AP1,PRKCB
Role of Tissue Factor SRC,CTGF,GNA 12,PIK3R5,PLAUR, Cancer MMP13,LIMK2,RPS6KA5,MAPK13,
JAK2,ARRB2,PAK1 ,MTOR,GNA 15,
PDXP,CDC42,MAPK3,LYN,PLCB 1 ,
IL1B,CXCL1,PIK3R2,RPS6KA2,
RPS6KA 1 ,C YR61 ,ΜΜΡ 1
Tec Kinase Signaling GTF2I,PIK3R5,TNFSF10,JAK2,GNG7,
PRKCZ,GNB4,PAK1,GNG11,GNA15,
RH0U,PIK3R2,GNG5,STAT1,
TNFRSF10A,VAV2,STAT6,SRC,
GNA12,MAPK9,ITGA5,PLCG1,
STAT3,GNG 10,BTK,STAT4,PRKCI,
WAS,VAV3,MAPK10,FCER1G,
LYN,FNBP1,PRKCB
STAT3 Pathway SRC,PTPN6,PTPN2,TGFBR3,
FGFR1,BMPR2,MAPK9,S0CS4,
JAK2,STAT3,MAPK13,IGF2R,
KIAA1804,BCL2,FGFR3,GHR,
MAPK3,MAPK10,CDC25A
Agranulocyte Adhesion M YH 10,IL 1 A,MMP7,CLDN 15 , and Diapedesis MMP 14,MMP 15 ,ΜΜΡ 13 ,CCL5,
CXCL9,MMP25,CCL4L1/CCL4L2,
ITGB7,HRH1,CCL13,CCL3L1,
CXCL13,CCL8,CCL2,CCL3L3,
EZR,CXCL 1 ,ΜΜΡ 1 , VC AM 1 ,
CXCL11,C5AR1,TNFRSF1 A,
CKLF,ITGA5,MYH7,MMP2,C5,
ITGB2,CCL4,IL1 RN,PEC AM 1 ,
IL1B,CD34,MMP9,CCL7
Role of NFAT in CSNK1G1,NFKBIE,PIK3R5,
Regulation of the HLA-DQ A 1 ,FCGR2B ,FCGR 1 A,
Immune Response GNG7,NFATC 1 ,1KB KB ,GNB4,
GNG 11 ,HL A -DRB 1 ,GN A 15 ,
HLA-DM A,MAPK3 ,HLA-DRA,
PLCB 1,PIK3R2,GNG5,FCGR1B,
CSNK1G2,GRB2,FCGR2A,
GNA 12,PLCG 1 ,1KB KE,GNG 10,
BTK,CD80,ITPR3,FCER1G, LYN,HLA-DOB ,CD86,LCP2,
HLA-DRB5
LPS/IL-1 Mediated 2.7E00 2E-01 ALDH4A 1 , APOEJL 1 A,CPT 1 B , Inhibition of RXR AP0C2,HS3ST3A1,CHST15, Function ABC A 1 ,ABCB9,IRAK1 ,IL1 R2,
CHST2,GSTM2, ALDH 1 A 1 ,
ALDH3A2,ACSL4,PPARGC1B,
TNFRSF 1 B , ALDH5 A 1 , ALDH6 A 1 ,
ALDH7A 1 ,SULT1 C2, ACOX2,
TNFRSF1A,MYD88,GSTA4,
NR1H3,MAPK9,GST01,IL4I1,
IL18RAP,LY96,IL1RN,SULT1A1,
C AT,CPT2,APOC 1 ,CD 14JL1B,
SLC27 A3 ,NDST2, ALDH 16A 1 ,
CHST13,RXRA
IL-10 Signaling 2.69E00 CCR 1 JL4RJL 1 A,FCGR2A,
01 NFKBIE,IKBKE,IL6,STAT3,
MAPK13,FCGR2B,IL18RAP,
IL1R2,IKBKB,IL1RN,IL10RA,
IL10RB,CD14,IL1B
Growth Hormone 2.62E00 2.61E- PTPN6,PIK3R5,PLCG1,S0CS4, Signaling 01 RPS6KA5,STAT3,JAK2,PRKCZ,
PRKCI,GHR,MAPK3,IGFBP3,
RPS6KA2,PIK3R2,RPS6KA 1 ,
STAT 1 , A2M,PRKCB
Cdc42 Signaling 2.61E00 FGD3 ,MPRIP,HLA- A,DIAPH3 ,
01 ARPC5 ,HLA-DQ A 1 ,LIMK2,
MAPK13,PRKCZ,HLA-G,IQGAP2,
PAK1 ,DIAPH 1 ,HLA-DRB 1 ,
PPP 1 R 12 A,HLA-DM A,HLA-DRB 3 ,
HLA-DRA,HLA-DPA 1 ,MYL 12 A,
VAV2,SRC,ITGA5,MAPK9,
WIPF1,HLA-DRB4,PRKCI,HLA-C,
WAS,CDC42, ARPC2,MAPK10,
FCER1 G,HLA-DOB ,HLA-DRB5
Cell Cycle: Gl/S 2.59E00 CCNE2,TFDP1,BMI1,ABL1,CDK6, Checkpoint Regulation 01 RBL1 ,CCND 1 ,SKP2,RB 1 ,CCNE1 ,
CDKN2D,MAX,E2F5,GNL3,E2F2,
CDK2,CDC25A
ATM Signaling 2.57E00 TRIM28,ABL1,MAPK9,MRE11A,
01 MAPK13,CBX5,SMC2,GADD45A, H2AFX,SMC 1 B ,ΜΑΡΚΙ 0,BID,BLM, BRCA1,CDK2,CDC25A
Oncostatin M Signaling 2.56E00 3.24E- TIMP3,EPAS 1 ,GRB2,MAPK3,
01 MMP13,OSM,STAT3,JAK2,
CHI3L1,STAT1,MMP1 Role of IL-17A 2.55E00 2.78E- NFKBIE,PIK3R5,MAPK9,
Arthritis 01 MMP13,MAPK13,CCL5,IL17RA,
CCL2,MAPK3,MAPK10,CXCL1, PIK3R2,RPS6KA 1 ,ΜΜΡΙ ,CCL7 phagosome formation 2.55E00 2.29E- PIK3R5,TLR8,FCGR2B,FCGR1A,
01 PRKCZ,PLCD3,TLR1,RH0U,TLR7, PLCB 1,PIK3R2,TLR3,FCGR1B, FCER2,FCGR2A,ITGA5,PLCG1, INPP5D,TLR2,CLEC7A,PRKCI, TLR6,FCER1G,FNBP1,PRKCB
Pathogenesis of Multiple 2.54E00 5.56E- CCR1,CXCL11,CCL4,CCL5,CXCL9 Sclerosis 01
Role of JAK family 2.54E00 3.6E- MAPK3,MAPK10,MAPK9,OSM, kinases in IL-6-type 01 STAT3,MAPK13,JAK2,IL6,STAT1 Cytokine Signaling
Aldosterone Signaling in 2.47E00 ICMT,SGK1 ,HSPA 1 A/HSPA IB , Epithelial Cells 01 PIK3R5,HSPA6,DNAJC13,
DNAJA 1 ,HSPA5 ,PRKCZ,
HSPA4,PLCD3,HSP90B1,
HSP90AB 1 ,DNAJC4,MAPK3, PLCB 1,PIK3R2,DNAJC9,
HSPH 1 ,SLC 12A2,PLCG 1 ,DNAJC2, DNAJB14,DNAJC5,PRKCI,PIP5K1C, HSCB,ITPR3,HSPB11,DNAJB6, DNAJB5,PRKCB
Retinoic acid Mediated 2.41E00 2.62E- PARP10,PARP2,IFNW1,ZC3HAV1, Apoptosis Signaling 01 TNFSF10,PARP12,IFNA10, IFNA14,
CRABP1 ,IFN A 16,PARP 15 ,IFN A7, BIDJFNA21 ,RXRA,TNFRSF 1 OA
IL-8 Signaling 2.4E00 2.01E- PIK3R5,LIMK2,CCND1,
01 GNG7,PRKCZ,BCL2,IRAK1,
RAB 11 FIP2JKB KB ,GNB 4,
MTOR,GNGl l,MAPK3,RHOU, CYBB,CXCL1,PIK3R2,GNG5, SRC,VC AM 1 ,GNA 12,MAPK9, MMP2JKB ΚΕ,Β AXJRAK3 , GNG 1 OJTGB 2, ARRB 2,PRKCI, ITGAM,ARAF,NCF2,MAPK10, FNBP1,MMP9,PRKCB
Breast Cancer 2.37E00 1.99E- PIK3R5,LIMK2,GNG7,PRKCZ, Regulation by Stathminl 01 STMN1,GNB4,PAK1,GNG11,
C AMK2D,PPP 1 R 12A,PPP 1 R7, MAPK3,E2F5,PLCB 1,ARHGEF3, PIK3R2,GNG5,E2F2,CAMK2B, CCNE2,GRB2,TUBG1,ADCY3, TUB A4A,PPP2R5 A,GNG 10,CCNE 1 , PRKCI,PPP2R4,CDC42,ARHGEF16, ADC Y 1 JTPR3 ,PRKAG2, ARHGEFl 0, ADCY7,CDK2,PRKCB
Polyamine Regulation in 2.34E00 3.64E- PSME1,TCF4,MAX,AZIN1,MXD1, Colon Cancer 01 PSME2,OAZ2,ODCl
Reelin Signaling in 2.3E00 2.41E- AP0E,SRC,CNR1,PIK3R5,ITGA5, Neurons 01 MAPK9,VLDLR,CDK5R1,APP,
ITGB2, ARHGEFl 6,MAPK10, LYN,LRP8,MAP4K1 ,PIK3R2,
ARHGEF3 , ARHGEFl 0,P AFAH 1 B 3
Macropinocyt( 2.3E00 2.5E- SRC,PDGFA,PIK3R5,PLCG1, Signaling 01 ITGA5,CSF1R,ITGB7,PRKCZ,
MET,ITGB2,PAK1 ,PRKCI, CDC42,CD 14,PIK3R2,PDGFD, PRKCB
fMLP Signaling 2.29E00 2.22E- FPR3,NFKBIE,APvPC5,FPR2, Neutrophils 01 PIK3R5,NFATC 1 ,PRKCZ,GNG7,
GNG 10,GNB4,NCF1 ,PRKCI, GNG11,WAS,CDC42,ARPC2, MAPK3,NCF2,ITPR3,CYBB, PLCB 1,PIK3R2,GNG5,PRKCB IL-1 Signaling 2.27E00 IL1A,MYD88,NFKBIE,GNA 12,
01 ADC Y3 ,M APK9JKB KE,IR AK3 , MAPK13,GNG7,IRAK1,GNG10, IKBKB,GNB4,GNG11,GNA15, ADC Y 1 ,ΜΑΡΚΙ 0,PRKAG2, GNG5,ADCY7
DNA Double-Strand 2.26E00 4.29E- LIG1,P0LA1,ABL1,MRE11A, Break Repair by 01 RPA1,BRCA1
Homologous
Recombination
Phenylalanine 2.26E00 ALDH2,ALDH3A2,GOT 1 , Degradation IV SLC27A3,G0T2,IL4I1
(Mammalian, via Side
Chain)
Renin-Angiotensin 2.24E00 2.2E- PTPN6,GRB2,ADCY3,PIK3R5, Signaling 01 PLCG1,MAPK9,CCL5,JAK2,
STAT3,MAPK13,PRKCZ,PAK1 ,
PRKCI,CCL2,MAPK3,ADCY1,
ITPR3,MAPK10,PRKAG2,PIK3R2,
PTGER2,STAT1,ADCY7,PRKCB IL-4 Signaling 2.2E00 2.4E- STAT6,PTPN6,IL4R,GRB2,
01 HLA-DQA1,PIK3R5,JAK2,
OCRL,NFATC 1 ,INPP5D,MTOR,
HLA-DRB 1 ,HLA-DMA,HLA-DRA,
HLA-DOB,PIK3R2,HLA-DRB5,
FCER2
Superpathway of Serine 2.15E00 5.71E- PS ATI ,PHGDH,SHMT 1 ,SHMT2 and Glycine Biosynthesis 01
I
B Cell Development 2.15E00 3.03E- IL7R,PTPRC,HLA-DRB 1 ,CD80,
01 HLA-DMA,HLA-DRA,HLA-DQA 1 , CD86,HLA-DOB,HLA-DRB5
GADD45 Signaling 2.14E00 3.68E- PCNA,CCNE2,CCNE 1 ,GADD45A,
01 BRCA1,CCND1,CDK2 Glucocorticoid Receptor 2.11 E00 1.82E- YWHAH,SGK1,HSPA1A HSPA1B, Signaling 01 GTF2E2,MAPK13,IL6,CD 163,HSPA5,
FCGR1A,IL1R2,HSPA4,IKBKB, BAG 1 ,M APK3 ,GTF2F 1 ,ST AT3 , TAF9B ,IL 1 RN,MAPK10,GTF2F2, POU2F2,NFKBIE,PIK3R5,HSPA6, JAK2,CCL5,NFATC 1,BCL2,GTF2A2, HSP90B 1 ,CCL13,HSP90AB 1 ,CCL2, NC0A2,ANXA1,PIK3R2,STAT1, MMP 1 ,GTF2H3,SRA 1 , VC AM 1 , GRB2,MAPK9,IKBKE,VIPR1, PRKAG2 L 1 B ,HLTF, A2M,T AF 1 L Methylmalonyl Pathway 2.11E00 7.5E- PCCA,PCCB,MUT
01
Chemokine Signaling 2.1E00 2.39E- CCR3,SRC,MPRIP,PLCG1,LIMK2,
01 MAPK13,CCL5,CAMK2D,CCL13, CCL4,PPP 1 R 12 A,CCL2,M APK3 , PLCB 1 ,C AMK2B ,PRKCB ,CCL7 Role of JAK1, JAK2 and 2.08E00 3.33E- PTPN6,PTPN2,IFNGR2,IFNA21, TYK2 in Interferon 01 STAT3,JAK2,STAT1,IFNAR2
Signaling
Role of IL- 17F in 2.08E00 2.73E- CCL4,CCL2,MAPK3,MMP13, Allergic Inflammatory 01 IL1B,RPS6KA5,CXCL1,
Airway Diseases RPS6KA2,IL6,RPS6KA1,
IL17RA,CCL7
iNOS Signaling 2.08E00 2.73E- IKBKB,LY96,MYD88,NFKBIE,
01 IFNGR2,CD14,IKBKE,MAPK13, JAK2,IRAK3,STAT1,IRAK1
Inhibition of Matrix 2.06E00 2.82E- TIMP3,MMP7,MMP14,MMP15, Metalloprote ase s 01 MMP13,MMP2,MMP25,A2M,
MMP9,MMP1,TIMP2
Role of JAK2 in 2.05E00 2.94E- PTPN6,GHR,EPOR,SOCS4,
Hormone-like Cytokine 01 STAT3,JAK2,PRLR,STAT 1 ,
Signaling HLTF,SIRPA
VDR/RXR Activation 2.02E00 2.31 E- SERPINB 1 ,SPP 1 ,PPARD,PDGFA,
01 IGFBP5,CCL5,THBD,PRKCZ,
PRKCI,GADD45A,NCOA2,
HOXA10,MXD 1 JGFBP3,
CD 14,C YP27B 1 ,RXRA,
PRKCB
iCOS-iCOSL Signaling 1.99E00 2.13E- GRB2,NFKBIE,PIK3R5,HLA- in T Helper Cells 01 DQA 1 ,PLCG 1 ,IKBKE,NFATC 1 ,
INPP5D,PTPRC,IKB KB ,
HLA-DRB 1 ,C AMK2D,CD80, HLA-DMA,HLA-DRA,ITPR3, FCER1 G,HLA-DOB ,PIK3R2, ICOSLG/LOC 102723996,
HLA-DRB 5 ,LCP2,C AMK2B
IL-17A Signaling in 1.96E00 3.2E- CXCL11,MAPK3,MAPK10,
Gastric Cells 01 MAPK9,CXCL1,MAPK13,
CCL5,IL17RA
IL-17A Signaling in 1.96E00 2.86E- 1KB KB ,CCL2,M APK3 ,NFKB IE, Fibroblasts 01 IKBKE,MAPK13,IL6,IL17RA,
MMP1,CCL7 Protein Ubiquitination 1.8E- HLA- A,HSPA 1 A HSPA 1 B , Pathway 01 HSPA6,DNAJC13, PSMB8,DNAJA1,
HSPA5, TAP1, SMURFl,
UBE2F,HSPA4,PAN2,
HSP90B1,HSP90AB1,
BAG 1 ,DNAJC4,UBE2V 1 ,
PSMA3,UBE2E3,BRCA1,
PSMA2,AMFR,DNAJC9,
HSPH 1 ,PSME2,DNAJC2,
USP1,USP33,DNAJB14,
SKP2,UCHL3,PSMD11,
PSME1 ,DNAJC5,UBE2J1 ,
CBL,HLA-C,HSCB,
CUL2,USP4,HSPB11,
USP37,DNAJB6,USP9Y,
DNAJB5,USP51
82 Toll-like Receptor 1.92E00 2.3E- IL1A,TICAM2,MYD88,TLR8,
Signaling 01 IRAK3,MAPK13 RAK1 ,TLR2,
1KB KB ,LY96,IL 1 RN,TLR 1 ,TLR6, TLR7,CD14,IL1B,TLR3
83 Regulation of Cellular 1.91E00 2.46E- SRC,GRB2,CDK6,ITGA5,
Mechanics by Calpain 01 CCND1,CNGA1,RB 1,CCNE1,
Protease TLN2,EZR,MAPK3,VCL,
CAPN7,CDK2
84 PPARa RXRa 1.91E00 1.91E- TGFB R3 ,CPT 1 B ,NFKB IE,
Activation 01 CD36,BMPR2,JAK2,IL6,
ABCA1,IL1R2,PLCD3,IKBKB, HSP90B 1 ,GN A 15 ,HSP90AB 1 , GPD2,MAPK3,PLCB1,G0T2, GRB2,ADCY3,PLCG1,IKBKE, BCL3,ACVR1B,IL18RAP,GHR, GK, ADC Y 1 ,PRKAG2,IL 1 B , RXRA,ADIPOR2,ADCY7,PRKCB
85 Salvage Pathways of 1.9E00 5E-01 APOBEC3B,TYMP,
Pyrimidine AP0BEC3A,TK1
Deoxyribonucleotides
86 IL-6 Signaling 1.9E00 2.07E- IL1 A,TNFRSF1 A,GRB2,
01 NFKBIE,PIK3R5,MAPK9,
IKBKE,IL6,JAK2,STAT3,
M APK13 ,IL 18RAPJL 1 R2,
IKBKB,CYP19A1,IL1RN,
MAPK3 ,M APK10,CD 14,
IL1B,PIK3R2,TNFRSF1B,
A2M,MCL1
p53 Signaling 1.89E00 2.14E- PIK3R5,PERP,BAX,HIF1A,
01 CCND1,BCL2,CCNG1,
SC02,RB 1 ,CASP6,PCNA,
GADD45A,GNL3,PIK3R2,
PIDD 1 ,PML,HIPK2,BRC Al , TNFRSF 10A,CDK2,DRAM 1
BER pathway 1.89E00 4.17E- LIG1,PCNA,PNKP,P0LE,FEN1
01 Hereditary Breast Cancer 1.87E00 2.02E- FANCG,TUBG1,CDK6,
Signaling 01 PIK3R5,RPA1,RFC1,
MRE11A,RFC5,CCND1, MLH 1 ,FANCE,PALB2,
FANCB,RB1,RFC4,MSH2, GADD45A,H2AFX,XPC, MSH6,RFC2,PIK3R2,BLM, B RCA 1 ,HLTF,RFC 3
Autoimmune Thyroid 1.84E00 2.55E- HLA-G,HLA-DRB 1,CD80, Disease Signaling 01 HLA-A,HLA-C,HLA-DMA,
HLA-DRA,HLA-DQA 1 , FCER1G,CD86,HLA-D0B, HLA-DRB5
PPAR Signaling 1.84E00 2.15E- IL1A,SRA1,TNFRSF1A,
01 GRB2,PPARD,PDGFA,
NFKB IE,NR 1 H3 ,1KB KE, IL 18RAPJL 1 R2 KB KB , HSP90B 1 ,HSP90AB 1 JL1RN, M APK3 ,IL 1 B ,RXRA,
TNFRSF 1 B ,PDGFD
Molecular Mechanisms 1.84E00 1.7E- FZD3,MAPK13,RBL1, of Cancer 01 CCND1,RB 1,PAK1,CAMK2D,
GNA15,MAPK3,PLCB1, HIPK2,BRCA1,RALGDS, E2F2,CDC25A,CCNE2,
TFDP1,BMP8B,CDK6,ITGA5, CBL,MAX,CDC42,ARHGEF16, APH 1 A,FZD6,MAPK10, ARHGEF10,CDK2,FNBP1, TCF4,NFKBIE,PIK3R5,
ABL 1 ,B MPR2,CRK,HIF 1 A, JAK2,PRKCZ,BCL2,CASP6, E2F5,RHOU,BID,PIK3R2, ARHGEF3 ,C AMK2B ,SRC ,GRB 2, GNA 12, ADC Y3 ,Μ APK9, BAX,CCNE1,CDKN2D,PRKCI, FZD4, ADC Y 1 ,PRKAG2, RBPJ,ADCY7,PRKCB
HER-2 Signaling in 1.8E00 2.24E- TSC1,CCNE2,GRB2,CDK6, Breast Cancer 01 PIK3R5,PLCG1,MMP2,
PARD6G,CCND 1 JTGB7, PRKCZ,ITGB2,CCNE1,
PRKCI,CDC42,PIK3R2,PRKCB
G Beta Gamma 1.79E00 2.16E- SRC,GRB2,GNA12,
Signaling 01 PLCG1,PRKCZ,GNG7,
GNG 10,BTK,GNB4,PAK1 , GNG11,PRKCI,GNA15, CDC42,MAPK3,ADCY1, PRKAG2,GNG5,PRKCB
UVA-Induced MAPK 1.79E00 2.16E- PARP10,PARP2,ZC3HAV1, Signaling 01 PIK3R5,PLCG1,MAPK9,
RPS6KA5,PARP12,MAPK13, PLCD3,MTOR,PARP15, MAPK3,MAPK10,PLCB 1, PIK3R2,RPS6KA2,RPS6KA1, STAT1
Histamine Degradation 1.79E00 3.53E- ALDH4A 1 , ALDH2,HNMT,
01 ALDH 1 A 1 , ALDH3 A2, ALDH7 A 1
Systemic Lupus 1.78E00 1.82E- IL1A,HLA-A,PIK3R5,IL6, Erythematosus Signalin 01 IFNA10,FCGR2B,IFNA14,
FCGR1 A,NFATC 1 ,HLA-G, PTPRC,SNRPN,MTOR, MAPK3,IFNA7,TLR7,
LSM3,PIK3R2,FCGR1B, LSM4,TNFSF13B ,PTPN6, GRB2,FCGR2A,PLCG 1 , INPP5D,C5,IFNA 16,LSM8, CBL,CD80,IL1RN,HLA-C, CD72,FCER1G,LYN,CD86, IL1BJFNA21
98 L-cysteine Degradation 1.78E00 1E00 MPST,GOTl
III
99 Glycine Biosynthesis I 1.78E00 1E00 SHMT1,SHMT2
100 G Protein Signaling 1.76E00 2.81E- GNB 4,GNG 11 , AB L 1 ,PLCG 1 , Mediated by Tubby 01 PLCB 1,JAK2,GNG5,GNG7,
GNG10
101 Role of Lipids/Lipid 1.76E00 3.18E- IFNA16,RSAD2,IFNW1,
Rafts in the Pathogenesis 01 IFNA7,IFNA21,IFNA10, of Influenza IFNA14
102 IL-3 Signaling 1.76E00 2.25E- STAT6,PTPN6,IL3RA,GRB2,
01 PIK3R5,STAT3,JAK2,INPP5D, PRKCZ,CSF2RB,PAK1,PRKCI, MAPK3,PIK3R2,STAT1,PRKCB
103 Lysine Degradation V 1.75E00 6E-01 A AD ΑΤ,ΡΙΡΟΧ, ALDH7 A 1
104 2-oxobutanoate 1.75E00 6E-01 PCCA,PCCB,MUT
Degradation I
105 PDGF Signaling 1.75E00 2.21E- SRC,GRB2,PDGFA,ABL1,
01 PIK3R5,PLCG1,CRK,JAK2,
STAT3,OCRL,INPP5D,MAPK3, SPHK1 ,PIK3R2,STAT1,PDGFD, PRKCB
OX40 Signaling Pathway 1.74E00 2.13E- TRAF3 ,HLA- A,NFKB IE,
01 HLA-DQA1,MAPK9,BCL2,
HLA-G,HLA-DRB 1 ,HLA-DRB4, HLA-DMA,HLA-C,HLA-DRB3, HLA-DRA,M APK10,FCER 1 G, HLA-DOB ,TR AF5 ,HLA-DRB5 , HLA-DPA1
107 Role of RIG 1 -like 1.73E00 2.56E- DHX58,IFN A 16,IKB KB ,TR AF3 ,
Receptors in Antiviral 01 NFKB IE,IFN A7,IFN A21 ,1KB KE, Innate Immunity TBK1,IFNA10,IFNA14 108 Huntington's Disease 1.73E00 SGK1,HSPA1A HSPA1B,
Signaling 01 HSPA6,PIK3R5,HSPA5,PRKCZ,
CDK5R1 ,GNG7,TGM2,NSF,CTSD, GNB4,CASP6,HSPA4,MTOR, GNG 11 ,GN A 15 ,M APK3 ,C ASP 1 , PLCB 1,PIK3R2,GNG5,NAPA, GRB2,RCOR3,GLS,PSME2,MAPK9, DNM3,BAX,ZDHHC 17,GNG 10, TAF9B ,PSME 1 ,PRKCI,DNAJC5 , CASP2,PENK,HTT,CAPN7,PRKCB
109 D-myo-inositol-5- 1.73E00 1.93E- PTPN2,PTPN23,EPHX2,PPIP5K1 , phosphate Metabolism 01 NUDT 14,NUDT2,H ACD2,PPM 1 K,
PPFIA2,PTPRC,MTMR6,PLCD3, ATP1A1,PPP1R12A,PTPR0,PPP1R7, PLCB 1 ,PALD 1 ,CDC25 A,PTPN6, PLCG 1 ,PPP2R5 A,TNS3,PDXP, PPP2R4,TPTE2,PTPN22,SIRPA
Thrombin Signaling 1.72E00 1.84E- MPRIP,F2RL3,PIK3R5,MAPK13,
01 GNG7,PRKCZ,PLCD3,IKBKB,
GNB4.GNG11,CAMK2D,GNA15, PPP1R12A,MAPK3,RH0U,PLCB 1, ARHGEF3 ,PIK3R2,GNG5 ,M YL 12 A, CAMK2B,SRC,GRB2,GNA12,ADCY3, PLCG1,GNG10,PRKCI,ARHGEF16, ADC Y 1 ,ITPR3 , ARHGEF 10, ADC Y7, FNBP1,PRKCB
GPCR-Mediated 1.69E00 ADCY3,PLCG1,PRKCZ,GNG7, Nutrient Sensing in 01 FFAR2,GNG10,PLCD3,GNG11, Enteroendocrine Cells PRKCI,GN A 15 ,GPBAR 1 , ADC Y 1 ,
ITPR3,PRKAG2,PLCB 1 ,GNG5, ADCY7,PRKCB
112 Differential Regulation 1.66E00 3.33E- CCL4,CCL2,IL1B,CXCL1,CCL5, of Cytokine Production 01 IL6
in Macrophages and T
Helper Cells by IL-17A
and IL-17F
113 Differential Regulation 1.65E00 3.04E- IL1A,CCL4,CCL2,IL1B,DEFB1,
of Cytokine Production 01 CXCL1,CCL5
in Intestinal Epithelial
Cells by IL-17A and IL- 17F
114 Tryptophan Degradation 1.65E00 3.04E- ALDH4A 1 , ALDH2, AKR 1 A 1 ,
X (Mammalian, via 01 ALDH 1 A 1 , ALDH3 A2,
Tryptamine) ALDH7A1JL4I1
115 Ethanol Degradation IV 1.65E00 3.04E- ALDH4A 1 , ALDH2, ALDH 1 A 1 ,
01 ALDH3 A2,C AT,GPX7,ALDH7A 1
116 Superpathway of Inositol 1.63E00 1.81E- PTPN2,PTPN23,EPHX2,PIK3R5, Phosphate Compounds 01 PPIP5K1,NUDT14,NUDT2,
HACD2,PPM1 K,PPFIA2,OCRL, PTPRC,MTMR6,PLCD3,ATP1A1, PPP1R12A,PTPR0,PPP1R7,PLCB1, PIK3R2,PALD 1 ,CDC25 A,PTPN6, PLCG 1 ,ITPKA,INPP5D,PPP2R5 A, TNS3,PI4K2A,PDXP,PPP2R4, PIP5K1C,TPTE2,PTPN22,SIRPA
117 Docosahexaenoic Acid 1.63E00 2.56E- PIK3R5,BIK,BID,IL1B,PIK3R2, (DHA) Signaling 01 BAX,BCL2A1,PNPLA2,APP,
BCL2
D-myo-inositol (1,4,5,6)- 1.94E- PTPN2,PTPN23,EPHX2,PPIP5K1 ,
Tetrakisphosphate 01 NUDT14,NUDT2,HACD2,PPM1K,
Biosynthesis PPFIA2,PTPRC,MTMR6,ATP1A1,
PPP1R12A,PPP1R7,PTPR0,PALD1, CDC25A,PTPN6,PPP2R5A,TNS3, PPP2R4,PDXP,TPTE2,PTPN22, SIRPA
D-myo-inositol (3,4,5,6)- 1.94E- PTPN2,PTPN23,EPHX2,PPIP5K1 , tetrakisphosphate 01 NUDT14,NUDT2,HACD2,PPM1K,
Biosynthesis PPFIA2,PTPRC,MTMR6,ATP1A1,
PPP1R12A,PPP1R7,PTPR0,PALD1, CDC25A,PTPN6,PPP2R5A,TNS3, PPP2R4,PDXP,TPTE2,PTPN22,SIRPA
B Cell Receptor 1.61E00 1.84E- P0U2F2,NFKBIE,ABL1,PIK3R5, Signaling 01 MAPK13,BCL6,FCGR2B,OCRL,
NFATCl,PTPRC,IKBKB,MTOR, CAMK2D,MAPK3,PIK3R2, CAMK2B,VAV2,PTPN6,
APBB 1IP,GRB2,FCGR2A,MAPK9, IKBKE,INPP5D,BTK,DAPP1, CDC42,VAV3,LYN,PIK3AP1, BCL2A1,PRKCB
121 GM-CSF Signaling 1.6E00 2.26E- GRB2,PIK3R5,STAT3,JAK2,
01 CCND1,CSF2RB,CAMK2D,
MAPK3,LYN,PIK3R2,BCL2A1, STAT 1 ,PRKCB ,C AMK2B
PI3K/AKT Signaling 1.6E00 1.95E- TSC 1 , YWHAH,GRB 2,NFKB IE,
01 ITGA5,IKBKE,JAK2,NOS3,
CCND 1 ,OCRL,INPP5D,
PPP2R5A,PRKCZ,BCL2,
YWHAQ KB KB ,MTOR,
HSP90B 1 ,HSP90AB 1 ,LIMS 1 , PPP2R4,MAPK3,PIK3R2,MCL1
Death Receptor 1.6E00 2.07E- TNFRSF 1 A,PARP 10,NFKBIE,
Signaling 01 PARP2,ZC3HAV1,TNFSF10,
TBK1,IKBKE,PARP12,BCL2, ACIN 1 ,1KB KB,C ASP6,CRADD, PARP15,CASP2,BID,TNFRSF1B, TNFRSF10A
FLT3 Signaling in 1.59E00 2.16E- STAT6,GRB2,FLT3,PIK3R5,
Hematopoietic 01 RPS6KA5,STAT3,MAPK13,
Progenitor Cells INPP5D,STAT4,MTOR,CBL,
MAPK3,RPS6KA2,PIK3R2, RPS6KA1,STAT1 125 14-3 -3 -mediated TSC 1 ,SRC,YWHAH,TNFRSF1A, Signaling GRB2,TUBG 1 ,PIK3R5,TUBA4A,
PLCG1,MAPK9,BAX,PRKCZ,
YWHAQ,PLCD3,PRKCI,CBL,
MAPK3,MAPK10,PLCB 1,PIK3R2,
RPS6KA1,AKT1S1,PRKCB
126 Signaling by Rho Family DIAPH3,ARPC5,PIK3R5,LIMK2, GTPases SEPT 11 ,GNG7,PRKCZ,STMN 1 ,
GNB4,PAK1,GNG11,GNA15,
PPP1R12A,MAPK3,EZR,RH0U,
CYBB,ARHGEF3,PIK3R2,
GNG5,MYL12A,SEPT5,SEPT4,
GNA 12JTGA5 ,Μ APK9,
CDC42EP4,KIAA 1804,GNG 10,
WIPF1,CDH2,PRKCI,PIP5K1C,
WAS,CDC42,ARPC2,ARHGEF16,
NCF2,MAPK10,ARHGEF10,FNBP1
3 -phosphoinositide PTPN2,PTPN23,EPHX2,PIK3R5, Biosynthesis PPIP5K1,NUDT14,NUDT2,
HACD2,PPM1 K,PPFIA2,PTPRC,
MTMR6, ATP 1 A 1 ,ΡΡΡ 1 R 12A,
PTPR0,PPP1R7,PALD 1 ,
PIK3R2,CDC25A,PTPN6,
PPP2R5A,TNS3,PI4K2A,
PIP5K1C,PDXP,PPP2R4,
TPTE2,PTPN22,SIRPA
128 Acute Phase Response TCF4,IL1A,SERPING1,NFKBIE, Signaling JAK2,MAPK13,IL6,IRAK1 ,
SERPIND 1 ,1KB KB ,MTOR,
SOD2,MAPK3,CFB,OSM,
PIK3R2,TNFRSF1B,C3,
TNFRSF1A,GRB2,MYD88,
MAPK9,IKBKE,SOCS4,
STAT3,CRABP1,C5,IL1RN,
IL1B,A2M,C2
129 Role of PKR in 1.55E00 2.5E- IKBKB,TRAF3,TNFRSF1A,
Interferon Induction and 01 NFKBIE,BID,IKBKE,TRAF5, Antiviral Response TLR3,STAT1,FCGR1A
130 B Cell Activating Factor 1.55E00 2.5E- 1KB KB ,TRAF3 ,NFKB IE,
Signaling 01 MAPK10,MAPK9,IKB KE,
MAPK13,TRAF5,TNFSF13B, NFATC1
131 PKC0 Signaling in T 1.55E00 1.95E- VAV2,GRB2,NFKBIE,PIK3R5, Lymphocytes 01 HLA-DQA1,PLCG1,IKBKE,
NFATC 1 ,1KB KB ,HLA-DRB 1 , CAMK2D,CD80,HLA-DMA, V AV3 ,MAPK3 ,HLA-DRA, FCER1G,CD86,HLA-D0B, PIK3R2,HLA-DRB5,LCP2, CAMK2B
132 IL-22 Signaling M APK3 ,IL 1 ORB ,ΜΑΡΚΙ 0,
MAPK9,STAT3,MAPK13, STAT1 CCR5 Signaling in 1.54E00 PLCG 1 ,MAPK9,MAPK13,
Macrophages 01 CCL5 ,PRKCZ,GNG7,GNG 10,
GNB4,GNG11,PRKCI,CCL4,
M APK10,FCER 1 G,GNG5 ,PRKCB
Pancreatic 1.53E00 1.98E- TFDP1,GRB2,ABL1,PIK3R5,
Adenocarcinoma 01 MAPK9,JAK2,STAT3,
Signaling CCND 1 ,BCL2,RB 1 ,CCNE 1 ,
CDC42,MAPK3,MAPK10,
E2F5,PIK3R2,STAT1,
RALGDS,MMP9,E2F2,CDK2
MSP-RON Signaling 1.53E00 2.39E- TLR2,C SF2RB ,ITGB 2,
Pathway 01 ITGAM,IL3RA,CCL2,
PIK3R5,PIK3R2,JAK2,
RPS6KA2,PRKCZ
136 Cell Cycle Regulation by 1.52E00 2.57E- RB1,CCNE2,CCNE1,
BTG Family Proteins 01 PPP2R4,E2F5,CCND1,
E2F2,CDK2,PPP2R5A
137 Glycine Betaine 1.51E00 4E-01 PIPOX,SHMTl,SDS,
Degradation SHMT2
138 CTLA4 Signaling in 1.5E00 2.05E- PTPN6,GRB2,HLA-A,
Cytotoxic T 01 AP1S2,PIK3R5,PLCG1,
Lymphocytes JAK2,CTLA4,PPP2R5A,
AP1G2,CD80,HLA-C,
PPP2R4,FCER1G,CD86,
PIK3R2,LCP2,PTPN22
Prostate Cancer 1.5E00 2.07E- CCNE2,TFDP1,GRB2,
Signaling 01 SRD5A1,NFKBIE,ABL1,
PIK3R5,CCND1,BCL2,
RB1,HSP90B 1,CCNE1,
MTOR,HSP90AB 1 ,MAPK3,
PIK3R2,CDK2
Calcium-induced T 2.19E- HLA-DQ A 1 ,PLCG 1 , ATP2 A3 , Lymphocyte Apoptosis 01 ATP2A2,PRKCZ,HLA-DRB 1 ,
PRKCI,HLA-DMA,HLA-DRA,
ITPR3,FCER1G,HLA-D0B,
HLA-DRB5,PRKCB
IL- 17 A Signaling in 1.49E00 NFKBIE,PIK3R5,MAPK9,
Airway Cells 01 IKBKE,IL6,STAT3,MAPK13,
J AK2JL 17R Α,ΙΚΒ KB ,
MAPK3,MAPK10,
CXCL1,PIK3R2
CXCR4 Signaling 1.48E00 1.84E- PIK3R5,CRK,GNG7,
01 PRKCZ,GNB4,PAK1,GNG11,
GNA15,MAPK3,RHOU,
PLCB 1,PIK3R2,GNG5,
MYL12A,SRC,GNA12,
ADC Y3 ,MAPK9,GNG 10,
PRKCI,ADCY1,ITPR3,
MAPK10,LYN, ADC Y7,
ELMO 1 ,FNBP 1 ,PRKCB 3 -phosphoinositide 1.46E00 1.85E- PTPN2,PTPN23,EPHX2,
Degradation 01 PPIP5K1,NUDT14,NUDT2,
HACD2,PPM1 K,PPFIA2,
OCRL,PTPRC,MTMR6,
ATP1A1,PPP1R12A,PTPR0,
PPP1 R7,PALD 1 ,CDC25A,
PTPN6,INPP5D,PPP2R5A,TNS3,
PPP2R4,PDXP,TPTE2,PTPN22,SIRPA
NAD biosynthesis II 1.45E00 3.33E- KM0,TD02,ABL1,
(from tryptophan) 01 ID01,NMNAT3
Non-Small Cell Lung 1.44E00 2.15E- RB 1 ,STK4,TFDP 1 ,GRB2,
Cancer Signaling 01 MAPK3,ITPR3,CDK6,
PIK3R5,ABL1,PLCG1,
PIK3R2,RXRA,CCND 1 ,
RASSF1
Sphingosine- 1 -phosphate 1.41E00 S1PR5,PDGFA,GNA12,
Signaling 01 ADCY3,PIK3R5,PLCG1,
ASAH1,S1PR3,PLCD3,
CASP6,CASP2,MAPK3,
ADCY1,SPHK1,CASP1,
RHOU,PLCB 1 ,PIK3R2,
PDGFD,ADCY7,FNBP1
Hepatic Cholestasis 1.4E00 IL 1 A,NFKB IE,IL6,
01 PRKCZ,IRAK1,IL1R2,
IKBKB,0SM,TNFRSF1B,
CYP27A1,TNFRSF1A,
MYD88,ADCY3,MAPK9,
NR 1 H3 ,1KB KEJRAK3 ,
IL18RAP,LY96,PRKCL
IL 1 RN, ADC Y 1 ,PRKAG2,
M APK10,CD 14JL1B ,RXRA,
ADCY7,PRKCB
Relaxin Signaling 1.4E00 1.85E- NFKB IE,GN A 12, ADC Y3,
01 PIK3R5,PDE4B,NOS3,GNG7,
PRKCZ,MPPE 1 ,GNG 10,
GNB 4,GNG 11 ,GN A 15 ,
MAPK3 ,RXFP 1 , ADC Y 1 ,
PDE1B,GUCY1A2,PRKAG2,
TDP2,PDE5A,PIK3R2,GNG5,
ADCY7,MMP9
Induction of Apopt< 1.39E00 2.17E- SLC25A4/TNFRSF1A,
by HIV1 01 NFKB ΙΕ,Μ APK9JKB KE,
B AX,BCL2,IKBKB ,ΜΑΡΚΙ 0,
BID,SLC25A10,TNFRSF1B,
SLC25A5
IGF-1 Signaling 1.39E00 1.96E- IGFBP4,CTGF,YWHAH,
01 GRB2,PIK3R5,SOCS4,
IGFBP5JAK2JGFBP7,
STAT3,PRKCZ,IGFBP2,
YWHAQ,PRKCI,MAPK3,
IGFBP3,PRKAG2,PIK3R2,
CYR61 151 Natural Killer Cell 1.37E00 1.91E- VAV2,PTPN6,LAIR1,
Signaling 01 TYROBP,GRB2,FCGR2A,
PIK3R5,PLCG1,LILRB 1,
OCRL,CD300A,INPP5D,
PRKCZ,PAK1,PRKCL
VAV3,MAPK3,FCER1G,
PIK3R2,LCP2,PRKCB
152 Antiproliferative Role of 1.37E00 2.69E- RB1,CCNE2,CCNE1,
TOB in T Cell Signaling 01 PABPC4,RPS6KA1,CDK2,SKP2
153 Purine Nucleotides De 1.36E00 3.64E- ADSSLl ,IMPDH2,PPAT,GART Novo Biosynthesis II 01
154 Actin Cytoskeleton 1.35E00 1.71E- MYH10,FGD3,MPRIP,
Signaling 01 PDGFA,DIAPH3,ARPC5,
PIK3R5,CRK,LIMK2,IQGAP2, PAK1 ,DIAPH2,DIAPH 1 ,
C YFIP2,PPP 1 R 12A,M APK3 , EZR,PFN2,VCL,PIK3R2,
TMSB10/TMSB4X,MYL 12 A, MATK,VAV2,GRB2,GNA12, ITG A5 ,M YH7,GIT 1 ,TLN2, PIP5K1C,WAS,CDC42,VAV3, ARPC2,CD14,PDGFD
155 LPS-stimulated MAPK 1.35E00 2.05E- NFKBIE,PIK3R5,MAPK9,
Signaling 01 IKBKE,MAPK13,PRKCZ,
IKBKB,PAK1,PRKCI,CDC42, MAPK3,MAPK10,CD 14,PIK3R2, PRKCB
156 Tryptophan Degradation 1.35E00 2.86E- KMO,ACAT2,TD02,
III (Eukaryotic) 01 AC AT 1 ,IDO 1 ,HADH
157 Putrescine Degradation 1.35E00 2.86E- ALDH4A 1 , ALDH2, ALDH 1 A 1 , III 01 ALDH3 A2, ALDH7 A 1 ,IL411
158 Cell Cycle: G2/M DNA 1.34E00 2.24E- YWHAQ,GADD45A,YWHAH, Damage Checkpoint 01 CKS1B,ABL1,PKMYT1,RPS6KA1, Regulation HIPK2,BRCA1,PRKCZ,SKP2
159 Erythropoietin Signaling 1.34E00 2.09E- SRC,PTPN6,EPOR,GRB2,
01 NFKBIE,PIK3R5,PLCG1,
JAK2,PRKCZ,PRKCI,CBL, MAPK3,PIK3R2,PRKCB
160 5 -aminoimidazole 1.34E00 6.67E- PPAT,GART
Ribonucleotide 01
Biosynthesis I
161 D-glucuronate 1.34E00 6.67E- AKR1A1,DCXR
Degradation I 01
162 Biotin-carboxyl Carrier 1.34E00 6.67E- ACACB,HLCS
Protein Assembly 01
163 Thiosulfate 1.34E00 6.67E- MPST,TST
Disproportionation III 01
(Rhodanese)
164 Glutamate Degradation 1.34E00 6.67E- GOTl,GOT2
II 01
165 Aspartate Biosynthesis 1.34E00 6.67E- GOTl,GOT2
01 Atherosclerosis APOE,CCR3,VCAMl, Signaling ILlA,APOM,APOA4,PDGFA,
CD36,MMP13,APOC2,IL6,
PLA2G7,TNFRSF 14, APOL 1 ,
PLA2G4A,ITGB2,CCL2,
IL1RN, AP0C1,IL1B,PDGFD,
MMP9,MMP1
167 April Mediated Signaling 1.31E00 2.37E- 1KB KB ,TRAF3 ,NFKB IE,
01 MAPK10,MAPK9,IKB KE,
MAPK13,TRAF5,NFATC 1
168 Noradrenaline and 1.31E00 2.37E- ALDH4A 1 , ALDH2, AKR 1 A 1 ,
Adrenaline Degradation 01 ALDH1A1 ,DHRS9,ALDH3A2,
PECR,ALDH7A1,IL4I1
169 Aspartate Degradation II 1.3E00 4.29E- GOTl,MDHl,GOT2
01
170 IL-15 Production 1.29E00 2.59E PRKCLTWFl JFNA21 ,JAK2,
01 IL6,STAT1,PRKCZ
171 Endothelin-1 Signaling 1.27E00 1.74E- PIK3R5,MAPK13,NOS3,
01 PLA2G7,PRKCZ,PLCD3,CASP6,
GNA15,MAPK3,CASP1,PLCB1,
PIK3R2,SRC,EDNRB,GRB2,
GNA 12, ADC Y3 ,PLCG 1 ,
MAPK9,PLA2G4A,PRKCI,
ARAF,C ASP2, ADC Y 1 JTPR3 ,
MAPK10,GUC Y 1 A2,PTGER2,
ADCY7,PRKCB
Glioblastoma Multiforme TSC1,FZD3,PDGFA,PIK3R5,
Signaling CCND 1 ,RB 1 ,PLCD3,MTOR,
MAPK3,RH0U,E2F5,PLCB1,
PIK3R2,E2F2,SRC,GRB2,
CDK6,PLCG 1 ,CCNE1 ,FZD4,
CDC42,ITPR3,FZD6,PDGFD,
CDK2,FNBP1
SAPK/JNK Signaling SH2D2A,GRB2,GNA12,PIK3R5,
MAPK9,CRK,NFATC 1 ,GNG7, GNG11,GADD45A,CDC42,
Z ΑΚ,Μ APK10,FCER 1 G,
MAP4K1 ,MAP4K5,PIK3R2,
GNG5
Role of PI3K/AKT IFN A 16,M APK3 ,NFKB IE,
Signaling in the IFNW1,IFNA7,PIK3R5,
Pathogenesis of IFNA21,CRK,PIK3R2,CCL5,
Influenza IFNA10,IFNA14,MLH1
NRF2-mediated AKR7 A2, AKR7 A3 ,
Oxidative Stress PPIB,MAF,PIK3R5,DNAJC 13, Response DNAJA 1 ,PRKCZ, AKR 1 A 1 ,
GSTM2,SOD2,DNAJC4,MAPK3,
PMF1/PMF1-BGLAP,F0SL1,
UBE2E3,PIK3R2,CBR1,DNAJC9,
GSTA4,MAPK9,DNAJB 14,MAFF,
GST01,DNAJC5,PRKCI,CAT,DNAJB6,
DNAJB5,EPHX1,PRKCB
176 Nur77 Signaling in T HLA-DRB 1 ,CD80,HLA-DMA,
Lymphocytes HLA-DRA, HLA-DQA1,
FCER1G,CD86,HLA-D0B, RXRA,HLA-DRB5,NFATC 1 ,BCL2
Acyl-CoA Hydrolysis 1.23E00 3.33E- ACOT2,ACOTl,ACOT7,
01 ACOT9
Fc Epsilon RI Signaling 1.21E00 1.85E- VAV2,GRB2,PIK3R5,
01 PLCG 1 ,MAPK9,MAPK13,
OCRL,INPP5D,PRKCZ,BTK,
PLA2G4A,PRKCI,VAV3,MAPK3, MAPK10,FCER 1G,LYN,PIK3R2, LCP2,PRKCB
Dopamine Degradation 1.21E00 2.5E- ALDH4A 1 , ALDH2, ALDH 1 A 1 ,
01 ALDH3 A2,SULT1 A 1 ,ALDH7A 1 JL4I1
Su eφathway of 1.21E00 2.5E- MVD,SQLE,ACAT2,
Cholesterol Biosynthi 01 AC AT 1 ,MSMO 1 ,LSS,TM7SF2
Apoptosis Signaling 1.2E00 1.91E- TNFRSF 1 A,NFKBIE,PLCG 1 ,
01 IKBKE,BAX,BCL2,ACIN1,
CASP6,IKBKB,MAPK3,
CASP2,BID,CAPN7,RPS6KA1,
TNFRSF 1 B ,B CL2 A 1 ,MCL 1
HIFla Signaling 1.2E00 1.86E- MMP7,MMP 14,MMP 15 ,
01 PIK3R5,MAPK9,MMP13,
MMP2,MAPK13,HIF1A,
MMP25,NOS3,SLC2A3,
P4HTM,CUL2,MAPK3,
MAPK10,PIK3R2,MMP9,
MMP1
Inhibition of 1.19E00 2.35E- CD47,CD36,GUCY1A2,
Angiogenesis by TSP1 01 MAPK10,MAPK9,MAPK13,
NOS3,MMP9
CNTF Signaling 1.18E00 2.12E- MTOR,GRB2,MAPK3,
01 PIK3R5,RPS6KA5,STAT3,
PIK3R2,JAK2,RPS6KA2,
RPS6KA1.STAT1
CD40 Signaling 1.15E00 2E-01 1KB KB ,TRAF3 ,Μ APK3 ,
NFKBIE,MAPK10,PIK3R5,
MAPK9,IKBKE,PIK3R2,
TRAF5,MAPK13,STAT3,FCER2
Melanocyte 1.15E00 1.9E- SRC,PTPN6,GRB2,ADCY3,
Development and 01 PIK3R5,PLCG1,CRK,RPS6KA5, Pigmentation Signaling BCL2,MAPK3,ADCY1,PRKAG2,
RPS6KA2,PIK3R2,RPS6KA 1 ,
ADCY7
Airway Pathology in 1.13E00 3.75E- MMP2,MMP9,MMP1
Chronic Obstructive 01
Pulmonary Disease
Superoxide Radicals 1.13E00 3.75E- SOD2,CAT,GPX7
Degradation 01
Tryptophan Degradation 1.13E00 3.75E- KMO,TD02,ID01
to 2-amino-3- 01
carboxymuconate
Semialdehyde Cyclins and Cell Cycle 1.13E00 CCNE2/TFDP 1 ,CDK6, ABL1 , Regulation 01 CCND 1 ,PPP2R5 A,SKP2,RB 1 ,
CDKN2D,CCNE1,PPP2R4,E2F5, E2F2,CDK2,CDC25A
UVB -Induced MAPK 1.13E00 2.08E- MTOR,PRKCI,MAPK3,MAPK10, Signaling 01 PIK3R5,MAPK9,RPS6KA5,
MAPK13,PIK3R2,PRKCZ,
PRKCB
Protein Kinase A 1.13E00 M YH 10,PTPN23 , YWH AH, Signaling 01 NOS3,YWHAQ,PTPRC,
GNB 4,PLCD3 ,C AMK2D,
PTPR0,PPP1R7,MAPK3,
PLCB 1,TDP2,CDC25A,
PTPN6,PTPRG,PTPN3,
PDE4B ,CNG A 1 ,GNG 10,
ITPR3,EYA3,PDE1B,H1F0,
SIRPA,HIST1H1C,FLNB,
TCF4,PTPN2,DUSP6,NFKBIE,
PRKCZ,GNG7,NFATC 1 ,ΜΡΡΕ 1 ,
CDKN3,AKAP2,PTPN4,GNG11,
PPP1R12A,RYR1,GNG5,MYL12A,
C AMK2B ,PTPRK, ADC Y3 ,
PLCG 1 ,P YGB , ANAPC 13 ,
ADD3,PRKCI,ADCY1,
CDC14B,KDELR3,PRKAG2,
PDE5A,ADCY7,PTPN22,PRKCB tRNA Splicing 1.13E00 2.29E- TSEN34,TSEN54,PDE 1 B ,TDP2,
01 PDE5 A,TRPT 1 ,PDE4B ,ΜΡΡΕ 1 Ethanol Degradation II 1.13E00 2.29E- ALDH4A 1 , ALDH2, AKR 1 A 1 ,
01 ALDH1A1 ,DHRS9,ALDH3A2, PECR, ALDH7 A 1
FcyRIIB Signaling in B 1.12E00 2.2E- BTK,GRB2,MAPK10,PIK3R5, Lymphocytes 01 LYN,MAPK9,PIK3R2,FCGR2B,
INPP5D
Oleate Biosynthesis II 1.12E00 3.08E- SCD,CYB5A,ALDH6A1,FADS1 (Animals) 01
Cholesterol Biosynthesis 1.12E00 3.08E- SQLE,MSMO 1 ,LSS,TM7SF2 I 01
Cholesterol Biosynthesis 1.12E00 3.08E- SQLE,MSMO 1 ,LSS,TM7SF2
II (via 24,25- 01
dihydrolanosterol)
Cholesterol Biosynthesis 1.12E00 3.08E- SQLE,MSMO 1 ,LSS,TM7SF2
III (via Desmosterol) 01
Role of Osteoblasts, 1.12E00 1.64E- IL1A,TCF4,SFRP2,FZD3,
Osteoclasts and 01 MMP 14,NFKBIE,PIK3R5 ,ΜΜΡ 13 , Chondrocytes in BMPR2,IL6,NFATC 1 ,SMURF1 , Rheumatoid Arthritis BCL2,IL1R2,IKBKB,MAPK3,
TRAF5 ,PIK3R2,TNFRSF 1 B ,
MMP1,SRC,SPP1,TNFRSF1A,
BMP8B,MAPK9,ITGA5,IKBKE,
CSF1R,IL18RAP,CBL,FZD4,IL1RN,
MAPK10,FZD6,IL1B,SFRP1 PTEN Signaling 1.1E00 1.78E- YWHAH,GRB2,TGFBR3,FGFR1,
01 PIK3R5,BMPR2,ITGA5,IKBKE, CCND 1 ,IGF2R,OCRL,PRKCZ, INPP5D,BCL2,FGFR3,IKBKB, GHR,CBL,CDC42,MAPK3,PIK3R2
Acute Myeloid 1.1E00 1.9E- TCF4,GRB2,FLT3,PIK3R5,
Leukemia Signalin 01 STAT3,CCND1,CSF1R,IDH1,
CSF2RB,MTOR,ARAF,MAPK3, IDH2,PIK3R2,PML
HGF Signaling 1.1E00 1.81E- GRB2,PIK3R5,PLCG1,ITGA5,
01 MAPK9,IL6,STAT3,CCND1,
PRKCZ,MET,PAK1 ,PRKCI,
CDC42,MAPK3,MAPK10,
PIK3R2,ELK3,CDK2,PRKCB
Triacylglycerol 1.1E00 2.5E- ABHD 12,CEL,MGLL,LIPG,
Degradation 01 NDST2,PNPLA2
Role of Cytokines in 1.08E00 2.04E- IFNA16,IL1A,IL1RN,IFNA7, Mediating 01 IL27,IL1B,IFNA21,IFNL1,IL6,
Communication between IFNA10JFNA14
Immune Cells
Unfolded protein 1.08E00 2.04E- HSPA4,HSP90B 1 JNSIG 1 ,HSPH1 , response 01 HSPA1A/HSPA1B,HSPA6,CD82,
HSPA5 ,CEBPG, AMFR,B CL2 Ephrin B Signaling 1.08E00 1.92E- VAV2,GNB4,PAK1,GNG11,CBL,
01 GNA15,CDC42,GNA12,VAV3,
EFNB 1 ,MAPK3 ,GNG5 ,GNG7, GNG10
Antioxidant Action of 1.08E00 1.82E- NFKB IE,PLCG 1 ,MAPK9,IKB KE, Vitamin C 01 JAK2,MAPK13,PLA2G7,GST01,
SLC2A3,SLC23A2,IKBKB,PLA2G4A,
CSF2RB,PLCD3,SLC23A1,MAPK3,
MAPK10,PLCB 1
Arsenate Detoxification I 1.08E00 5E-01 GLRX2,GST01
(Glutaredoxin)
Phenylethylamine 1.08E00 5E-01 ALDH2,ALDH3A2
Degradation I
Arginine Degradation I 1.08E00 5E-01 ALDH4Al,OAT
(Arginase Pathway)
L-cysteine Degradation I 1.08E00 5E-01 GOTl,GOT2
N-acetylglucosamine 1.08E00 5E-01 NAGK,GNPDA2
Degradation II
Fatty Acid β-oxidation 1.08E00 5E-01 ECI2,ECI1
III (Unsaturated, Odd
Number)
UVC -Induced MAPK 1.07E00 2.14E- SRC,PRKCI,ARAF,MAPK3,
Signaling 01 MAPK10,MAPK9,MAPK13,
PRKCZ,PRKCB
Oxidative Ethanol 1.05E00 2.63E- ALDH4A 1 , ALDH2, ALDH 1 A 1 , Degradation III 01 ALDH3 A2, ALDH7 A 1
Neuropathic Pain 1.04E00 1.8E- SRC,KCNN4,PIK3R5,PLCG1, Signaling In Dorsal Horn 01 KCNN2,PRKCZ,GRIN3A,
Neurons GRINA,PLCD3,CAMK2D,
PRKCI,MAPK3,ITPR3,PRKAG2, PLCB 1,PIK3R2,CAMK2B,PRKCB God Signaling 1.04E00 1.75E- SRC,GRB2,CNR1,ADCY3,
01 FPR2,ADORA3,STAT3,
RGS12,GNG7,0PRL1,
GNG10,S1PR3,GNB4,
GNG 11 ,R AP 1 G ΑΡ,Μ APK3 ,
ADC Y 1 ,PRKAG2,GNG5 ,
ADCY7,RALGDS
-Adrenergic Signaling 1.04E00 1.84E- ADCY3,PLCG1,PYGB,PRKCZ,
01 GNG7,GNG10,GNB4,GNG11,
PRKCI,MAPK3,ADCY1,ITPR3,
PRKAG2,GNG5,ADCY7,PRKCB
Bladder Cancer 1.04E00 1.84E- MMP7,TFDP 1 ,ΜΜΡ 14,MMP 15 , Signaling 01 ABL1,MMP13,RPS6KA5,MMP2,
MMP25 ,CCND 1 ,FGFR3 ,RB 1 ,
MAPK3,MMP9,MMP1,RASSF1
Thrombopoietin 1.04E00 2E-01 PRKCI,GRB2,MAPK3,PIK3R5, Signaling PLCG1,STAT3,PIK3R2,JAK2,
STAT 1 ,PRKCZ,PRKCB
TNFR1 Signaling 1.03E00 CASP6,IKBKB,PAK1,
01 CRADD,TNFRSF1A,
CDC42,CASP2,NFKBIE,
BIDJKBKE
Isoleucine Degradation I 1.02E00 2.86E- ACAT2,ACAD8,ACAT1,
01 SDS
Superpathway of 1.02E00 2.86E- GLS,OAT,NOS3,
Citrulline Metabolism 01 CPS1
Colanic Acid Building 1.02E00 2.86E- GMPPB,UGP2,PMM1,
Blocks Biosynthesis 01 GALT
4- IBB Signaling in T 1.01E00 2.26E- 1KB KB ,M APK3 ,NFKB IE, Lymphocytes 01 MAPK10,MAPK9,IKB KE,
MAPK13
Neuregulin Signaling 1.01E00 1.82E- SRC,GRB2,DCN,PLCG1,ITGA5,
01 CRK,CDK5R1,PRKCZ,
MTOR,HSP90B 1 ,PRKCI,
HSP90AB 1 ,MAPK3,PIK3R2,
PRKCB,MATK
Leucine Degradation I 1E00 3.33E- MCCC 1 ,AC ADM,MCCC2
01
Ketolysis 1E00 3.33E- ACAT2,ACATl,OXCTl
01
UDP-N-acetyl-D- 1E00 3.33E- HK1,GNPDA2,UAP1 galactosamine 01
Biosynthesis II
Folate Transformations I 1E00 3.33E- MTHFR,SHMT1,SHMT2
01
Actin Nucleation by 9.95E-01 1.96E- WIPF1,PPP1R12A,GRB2, ARP-WASP Complex 01 WAS,CDC42,ARPC2,
GNA 12, ARPC5 ,RHOU,
ITGA5,FNBP1
EGF Signaling 9.95E-01 1.96E- SRC,MTOR,GRB2,
01 MAPK3,ITPR3,PIK3R5, PLCG1,STAT3,MAPK13,
PIK3R2,STAT1
Fatty Acid a-oxidation 9.73E-01 2.5E- ALDH4A 1 , ALDH2,
01 ALDH 1 A 1 , ALDH3 A2,
ALDH7A1
Vims Entry via 9.72E-01 1.8E- FLNB,SRC,HLA-A,
Endocytic Pathways 01 ABL1,PIK3R5,PLCG1,
ITGA5,ITGB7,PRKCZ,
ITGB2,AP1G2,PRKCI,
HLA-C,CDC42,PIK3R2,
PRKCB
Antiproliferative Role of 9.69E-01 1.9E- SRC,GNB4,PTPN6,
Somatostatin Receptor 2 01 GNG11,SSTR2,MAPK3,
GUCY1A2,PIK3R5,
PIK3R2,GNG5,GNG7,
GNG10
Role of Wnt/GSK-3 9.68E-01 1.84E- IFNA16,TCF4,DVL2, Signaling in the 01 FZD4,CSNK1G 1 ,NCOA2, Pathogenesis of CSNK1 G2,FZD3,IFNW 1 , Influenza IFNA7,FZD6,IFNA21,
IFNA10JFNA14
Type II Diabetes 9.63E-01 TNFRSF1A,CD36,
Mellitus Signaling 01 NFKBIE,PIK3R5,MAPK9,
SOCS4,IKBKE,PRKCZ,
IKBKB,MTOR,PRKCI,
MAPK3,MAPK10,
PRKAG2,ACSL4,PIK3R2,
SLC27A3,ADIPOR2,
TNFRSF1B,PRKCB
Fatty Acid β-oxidation I 9.56E-01 2.19E ECI2,ACSL4,SLC27A3,
01 SDS,ACADM,ECI1,
HADH
Superpathway of 9.56E-01 2.19E PCCA,GOTl,PCCB,
Methionine Degradation 01 AHCYL2,MUT,GOT2,
suox
Clathrin-mediated 9.5E-01 1.62E APOE,RAB5C,
Endocytosis Signaling 01 APOA4,PDGFA,ARPC5,
PIK3R5,APOC2,ITGB7,
CD2 AP, AP 1 G2,LDLR AP 1 ,
SH3GLB2,PIK3R2,SRC,
APOM,GRB2,ITG A5 ,DNM3 ,
APOLl ,MET,SH3GL1 ,ITGB2,
ARRB2,LDLR,CBL,PIP5K1C,
CDC42,ARPC2,AP0C1,
PDGFD CCR3 Signaling in 9.35E-01 1.71E CCR3,MPRIP,PIK3R5, Eosinophils 01 LIMK2,MAPK13,PRKCZ,
GNG7,GNG 10,GNB 4,
PLA2G4A,PAK1 ,PRKCI,
GNG11,PPP1R12A,
MAPK3,ITPR3,PLCB1,
PIK3R2,GNG5,PRKCB
Vitamin-C Transport 9.26E-01 2.67E SLC23A2,SLC23A1,
01 SLC2A3,GST01 244 Ovarian Cancer 9.24E-01 1.68E- SRC,TCF4,MMP7,
Signaling 01 TFDP 1 ,FZD3,ABL1 ,
PIK3R5,MMP2,CCND1, MLH 1 ,BCL2,RB 1 ,MTOR, FZD4,MSH2,MAPK3, MSH6,PRKAG2,FZD6, PIK3R2,BRC A 1 ,MMP9
245 Allograft Rejection 9.19E-01 1.79E- HLA-A,HLA-DQA1 ,HLA-G, Signaling 01 HLA-DRB 1,HLA-DRB4,
CD80,HLA-DMA,HLA-C, HLA-DRB3,HLA-DRA, FCER 1 G,HLA-DOB ,
CD86,HLA-DRB5,
HLA-DPA1
246 Androgen Signaling 9.14E-01 1.71E- SRC,GNA12,GTF2F1,
01 GTF2E2,CCND1,PRKCZ,
GNG7 ,GNG 10,GNB 4,HSP A4, GNG 11 ,PRKCLNCO A2, GNA 15,MAPK3,PRKAG2, GNG5 ,GTF2H3 ,PRKCB
247 Myc Mediated Apoptosis 9.12E-01 1.9E- YWHAQ,YWHAH,
Signaling 01 GRB2,MAPK10,PIK3R5,
MAPK9,BID,PIK3R2, BAX,PRKCZ,BCL2
248 Ceramide Biosynthesis 8.93E-01 4E-01 SPTLC2,KDSR
249 Serine Biosynthesis 8.93E-01 4E-01 PSAT1,PHGDH
250 Tetrapyrrole 8.93E-01 4E-01 UROS,ALAD
Biosynthesis II
251 Lysine Degradation II 8.93E-01 4E-01 A AD AT, ALDH7 A 1
252 Galactose Degradation I 8.93E-01 4E-01 GALT,GALM
(Leloir Pathway)
253 Folate Polyglutamylation 8.93E-01 4E-01 SHMT1,SHMT2
254 Glutamate Removal from 8.88E-01 1E00 GGH
Folates
255 Lanosterol Biosynthesis 8.88E-01 1E00 LSS
256 Sulfite Oxidation IV 8.88E-01 1E00 SUOX
257 p70S6K Signaling 8.81E-01 1.68E- SRC,IL4R,YWHAH,F2RL3,
01 GRB2,PIK3R5,PLCG1,
PPP2R5A,PRKCZ,BTK,
YWHAQ,PLCD3,MTOR, PRKCI,PPP2R4,MAPK3, LYN,PLCB 1 ,PIK3R2,PRKCB
258 P2Y Purigenic Receptor 8.81E-01 1.68E- P2RY11,ADCY3,PIK3R5, Signaling Pathway 01 PLCG1,PRKCZ,GNG7,
GNG10,GNB4,PLCD3, GNG11,PRKCI,P2RY6, M APK3 , ADC Y 1 ,PRKAG2 , PLCB 1,PIK3R2,GNG5, ADCY7,PR CB
259 Factors Promoting 8.78E-01 1.74E- CCNE2,TCF4,FZD3,TGFBR3, Cardiogenesis in 01 BMP8B,CDC6,BMPR2,MYH7, Vertebrates PR CZ,ACVR1B,CCNE1,
PRKCI,FZD4,FZD6,CDK2, PRKCB
260 JAK/Stat Signaling 8.78E-01 1.81E- STAT4,STAT6,MTOR,
01 PTPN6,GRB2,MAPK3,
PIK3R5,SOCS4,PIK3R2,
JAK2,STAT3,IL6,STAT 1
261 Gaq Signaling 8.69E-01 1.63E- HTR2B ,NFKB IE,PIK3R5 ,
01 PLCG 1 ,1KB KE,NFATC 1 ,
GNG7,PRKCZ,GNG10,BTK, 1KB KB ,GNB 4,HRH 1 ,PRKCI, GNG 11 ,GN A 15 ,M APK3 ,ITPR3 , RH0U,PLCB1,PIK3R2,GNG5, FNB PI, PRKCB
262 Methylglyoxal 8.45E-01 2.5E- AKR7 A2, AKR7 A3 , AKR 1 A 1 ,
Degradation III 01 AKR1B 1
263 RAR Activation 8.45E-01 1.58E- NR2F2,JAK2,MAPK13,PRKCZ,
01 TNIP1,ALDH1A1,S0RBS3,
PIK3R2,MMP1,GTF2H3,SRC,
SRA1,DHRS3,IL3RA,ADCY3,
MAPK9,CRABP1,CSF2RB,
PRKCI,DHRS9,ADCY1,
PRKAG2,IGFBP3,MAPK10,
RDH5,RXRA,PML,ADCY7,
HLTF,PRKCB
264 Prolactin Signaling 8.44E-01 1.78E- PRKCI,GRB2,MAPK3,PIK3R5,
01 PLCG1,S0CS4,STAT3,PIK3R2, JAK2,PRLR,STAT1,PRKCZ, PRKCB
265 Axonal Guidance 8.42E-01 1.47E- FZD3,ARPC5,SEMA6B,MMP13, Signaling 01 LIMK2, AD AMTS2,GNB 4,PLCD3 ,
PAK1 ,GNA 15 , AD AM28,M APK3 , PLCB 1,SRGAP2,BMP8B,ITGA5, MMP2,GNG 10,MET,HERC2, CDC42,ARPC2,FZD6,PDGFD, NRP1 ,ERAP2,MMP7,PDGFA, ABL1,PIK3R5,CRK,R0B01, PRKCZ,GNG7,NFATC 1 ,GNG 11 , EFNB 1,ADAM19,PFN2,LNPEP, SEMA4A,PIK3R2,GNG5,
MYL12A,PLXNC1,ADAM15, GRB2,GNA 12,TUBG1 ,TUB A4A, PLCG1,R0B03,GIT1,SEMA3A, WIPF1 ,SEMA4D,PRKCI,FZD4, WAS,PRKAG2,SEMA4B,ADAM9, MMP9,PRKCB
266 Nitric Oxide Signaling in 8.42E-01 1.7E- PIK3R5,SLC7Al,ATP2A3,NOS3, the Cardiovascular 01 ATP2A2,PRKCZ,HSP90B 1,PRKCI, System HSP90AB1,MAPK3,PDE1B,ITPR3,
GUC Y 1 A2,PRKAG2,PDE5 A,PIK3R2, PRKCB eNOS Signaling 8.24E-01 1.62E- HSPA 1 A/HSP A 1 B , ADC Y3 ,HSP A6,
01 PIK3R5,SLC7A1,PLCG1,HSPA5,N0S3,
CNGA 1 ,PRKCZ,HSP A4,HSP90B 1 ,LPAR6, PRKCI,LPAR2,HSP90AB 1 ,ADCY 1 JTPR3, GUC Y 1 A2,PRKAG2,PIK3R2,ADC Y7,PRKCB
Lymphotoxin β Receptor 8.15E-01 1.85E- IKBKB,TRAF3,VCAM1,MAPK3,PIK3R5, Signaling 01 IKBKE,CXCL1,TRAF5,LTBR,PIK3R2
Paxillin Signaling 8.14E-01 1.68E- SRC,GRB2,PIK3R5,ITGA5,MAPK9,CRK,
01 MAPKl 3,ITGB7,ITGAE,ITGB2,PAK1 JTGAM, TLN2,CDC42,MAPK10,PIK3R2, VCL
Leptin Signaling in 8.11E-01 1.76E- PLCD3,GRB2,MAPK3,ADCY1,ADCY3, Obesity 01 PRKAG2,PIK3R5,PLCB1,PLCG1,PIK3R2,
JAK2,STAT3,ADCY7
Cellular Effects of 8.03E-01 1.63E- MYH 10,KCNN4,MPRIP,ADCY3,PLCG 1 , Sildenafil (Viagra) 01 MYH7,KCNN2,PDE4B,NOS3,PLCD3,
PPP1R12A,PABPC4,ADCY1,ITPR3,
PDE1B ,GUCY 1 A2,PRKAG2,PLCB 1 ,
PDE5A,ADCY7,MYL12A
GNRH Signaling 8.03E-01 1.63E- SRC,GRB2,ADCY3,DNM3,MAPK9,
01 MAPKl 3,PRKCZ,PAK1 ,C AMK2D,
PRKCI,GN A 15 ,CDC42,MAPK3 , ADC Y 1 ,
ITPR3,MAPK10,PRKAG2,PLCB1,
ADCY7,CAMK2B,PRKCB
Glycogen Degradation II 7.92E-01 2.73E- PGM 1 ,P YGB ,T YMP
01
Gas Signaling 7.84E-01 1.65E- SRC.CNR 1 ,ADCY3,CNGA 1 ,GNG7,
01 GNG10,GNB4,GNG11,ADD3,RAPGEF2, VIPR 1 ,MAPK3, ADC Y 1 ,PRKAG2,RYR 1 , PTGER2,GNG5 , ADC Y7
Xenobiotic Metabolism 7.79E-01 ALDH4A1,IL1A,MAF,PIK3R5,MAPK13, Signaling 01 IL6,PRKCZ,HS3ST3A1,CHST15,CHST2,
HSP90B 1 ,C AMK2D, ALDH1 A 1 ,GSTM2, HSP90AB 1 ,MAPK3,ALDH3A2,PIK3R2, ALDH5 A 1 , ALDH6 A 1 , ALDH7 A 1 ,
CAMK2B,SRA 1 ,SULT 1 C2,GSTA4,
MAPK9,GSTO 1 ,C YP IB 1 ,PPP2R5A,
IL411 , AHRR,PRKCI,PPP2R4,SULT 1 A 1 , CATJL1B ,NDST2, ALDH 16 A 1 ,CHST 13 , RXRA,PRKCB
γ-linolenate Biosynthesis 7.73E-01 2.35E- ACSL4,SLC27A3,CYB5A,FADS 1
II (Animals) 01
Mitochondrial L- 7.73E-01 2.35E- CPT 1 B,CPT2,ACSL4,SLC27A3
carnitine Shuttle 01
Pathway
PAK Signaling 7.68E-01 1.69E- PAK1,ARHGAP10,CDC42,PDGFA,
01 GRB2,MAPK3,MAPK10,PIK3R5,
MAPK9,ITGA5,LIMK2,PIK3R2,
PDGFD,GIT 1 ,M YL 12 A
Role of JAK1 and JAK3 7.66E-01 1.77E- IL7R,STAT6,IL4R,IL15RA,GRB2,
in yc Cytokine Signaling 01 MAPK3,PIK3R5,STAT3,PIK3R2,
JAK2,STAT1 Phospholipase C 7.65E-01 1.52E- MPRIP,FCGR2B ,NFATC 1 ,GNG7,
Signaling 01 PRKCZ,TGM2,GNB4,GNG11,
PPP1R12A,MAPK3,RH0U,PLCB 1, ARHGEF3 ,GNG5 ,RALGDS,M YL 12 A, SRC,GRB 2,FCGR2A, ADC Y3 TGA5 , PLCG 1 ,GNG 10,BTK,PLA2G4A,
PRKCI,ARHGEF16,ADCY1 JTPR3, FCER 1 G,LYN, ARHGEF 10, ADC Y7, LCP2,FNBP1,PRKCB
Gal2/13 Signaling 7.58E-01 1.62E- VAV2,SRC,F2RL3,NFKBIE,GNA12,
01 PIK3R5 ,M APK9JKB ΚΕ,Β ΤΚ,ΙΚΒ KB , LPAR6,CDH2,LPAR2,CDC42,VAV3, MAPK3,MAPK10,PIK3R2,MYL12A p38 MAPK Signaling 7.58E-01 1.62E- IL 1 A,TIFA,TNFRSF1 A,HMGN 1 ,
01 RPS6KA5,IRAK3,MAPK13,IRAK1,
IL18RAP,IL1R2,PLA2G4A,MAX,
IL 1 RNJL 1 B ,M AP4K1 ,RPS6KA2,
RPS6KA 1 ,STAT 1 ,TNFRSF1B
Proline Biosynthesis II 7.54E-01 3.33E- OAT,PYCR2
(from Arginine) 01
Arginine Degradation VI 7.54E-01 3.33E- OAT,PYCR2
(Arginase 2 Pathway) 01
Glycerol Degradation I 7.54E-01 3.33E- GK,GPD2
01
Zymosterol Biosynthesis 7.54E-01 3.33E- MSM01,TM7SF2
01
Glycogen Biosynthesis II 7.54E-01 3.33E- UGP2,GBE1
(from UDP-D-Glucose) 01
GDP-mannose 7.54E-01 3.33E- GMPPB,PMM1
Biosynthesis 01
Stearate Biosynthesis I 7.54E-01 1.94E- ACOT2,SRD5A3,ACOTl,ACSL4,SLC27A3, (Animals) 01 ACOT7,ACOT9
Ephrin Receptor 7.42E-01 1.55E- PDGFA, ARPC5 , AB L 1 ,LIMK2,CRK, J AK2, Signaling 01 GNG7,GRINA,GNB 4,PAK1 ,GNG 11 ,GNA 15 ,
EFNB 1 ,MAPK3 ,GNG5 ,SRC,GRB 2,GNA 12, ITGA5,STAT3,GNG10,GRIN3A,WIPF1, WAS,CDC42,ARPC2,PDGFD
Rac Signaling 7.36E-01 1.63E- ARPC5,PIK3R5,ITGA5,LIMK2,CDK5R1,
01 PRKCZ,PAK1 ,IQGAP2,C YFIP2,PRKCI, CDC42,PIP5K1C,ARPC2,MAPK3,NCF2, CYBB,PIK3R2
IL-15 Signaling 7.32E-01 1.75E- STAT6,VCAM1,IL15RA,MAPK3,PIK3R5,
01 PLCGl ,STAT3,MAPK13,PIK3R2,JAK2,IL6 ERK5 Signaling 7.32E-01 1.75E- SH2D2A,YWHAQ,SRC,YWHAH,
01 SGK1,GNA12,RPS6KA5,F0SL1,
RPS6KA2,RPS6KA1,PRKCZ
Melatonin Signaling 7.25E-01 1.71E- PLCD3,PRKCI,CAMK2D,ARAF,
01 MAPK3,PRKAG2,PLCG1,PLCB 1,
PRKCZ,RORB ,C AMK2B ,PRKCB
Cardiac β-adrenerj 7.13E-01 1.58E- ADCY3,ATP2A3,PDE4B,ATP2A2,
Signaling 01 PPP2R5 A,GNG7,MPPE 1 ,GNG 10,
AKAP2,GNB4,GNG11,PPP1R12A,
PPP2R4,PPP1R7,ADCY1,PDE1B,
PRKAG2,TDP2,PDE5A,GNG5, ADCY7
296 Glutaryl-CoA 7.09E-01 2.5E- AC AT2, AC AT 1 ,HADH
Degradation 01
297 Glioma Invasiveness 7.08E-01 1.75E- TIMP3,MAPK3,PIK3R5,RHOU,
Signaling 01 PLAUR,MMP2,PIK3R2,MMP9,
FNBP1/TIMP2
298 Valine Degradation I 7.08E-01 2.22E- HIBADH,ACAD8,SDS,ALDH6A1
01
299 Pyridoxal 5'-phosphate 7.01E-01 1.72E- PAK1 ,FAM20B,ARAF,SGK1 ,
Salvage Pathway 01 MAPK3,CDK6,MAPK9,GRK5,
LIMK2,CDK2,IRAK1
300 Gap Junction Signaling 6.97E-01 1.55E- SRCDBN 1 ,HTR2B ,CSNK1G 1 ,
01 GRB2,CSNK1 G2,TUBG 1 , ADC Y3,
PIK3R5,TUBA4A,PLCG1,PRKCZ,
PLCD3,PRKCI,MAPK3,ADCY1,
ITPR3,GUCY1A2,SGSM3,PRKAG2,
PLCB 1,PIK3R2,ADCY7,PRKCB
301 Caveolar-mediated 6.95E-01 1.69E- ITGAE,ITGB2,FLNB ,SRC,ITGAM, Endocytosis Signaling 01 RAB5C,HLA-A,HLA-C,ABL1,
ITG A5 ,FLOT 1 ,ITGB 7
302 GPCR-Mediated 6.95E-01 1.69E- PLCD3,GRPR,VIPR1,GNA15,NMB, Integration of 01 ADCY1,ITPR3,ADCY3,PRKAG2,
Enteroendocrine PLCG 1, PLCB 1, ADC Y7
Signaling Exemplified
by an L Cell
303 TR/RXR Activation 6.89E-01 1.65E- UCP2,PIK3R5,NRGN,BCL3,PFKP,
01 HIF1A,KLF9,MT0R,SLC16A3,LDLR,
NCOA2,STRBP,PIK3R2,RXRA
304 Regulation of the 6.89E-01 1.52E- TCF4,FZD3,PIK3R5,TWIST1,PARD6G, Epithelial-Mesenchymal 01 J AK2,HIF 1 A,SMURF 1 ,FGFR3 ,Μ APK3 , Transition Pathway PIK3R2,JAG2,GRB2,FGFR1,MMP2,
STAT3,MET,PYG02,DVL2,CDH2,
FZD4,ARAF,APH1A,FZD6,RBPJ,
JAG1,PDGFD,MMP9
305 HMGB1 Signaling 6.89E-01 1.58E- VCAM1,IL1A,TNFRSF1A,RBBP7,
01 PIK3R5,IFNGR2,MAPK9,IL6,
MAPK13,CCL2,CDC42,MAPK3,
MAPK10,RHOU,OSM,IL1B,
PIK3R2,TNFRSF1B,FNBP1
306 Notch Signaling 6.7E-01 1.84E- JAG2,DTX3,APH1A,RBPJ,
01 JAG1,DLL4,DTX2
307 Gustation Pathway 6.67E-01 1.57E- P2R Y 11 , ADC Y3 ,PDE4B ,ΡΑΝΧ 1 ,
01 GNG7,MPPE 1 ,LPAR6,GNG 11 ,
PKD2L1,P2RY6,ADCY1,PDE1B,
ITPR3,PRKAG2,TDP2,PDE5A,
P2RY8,GNG5,ADCY7
308 IL-17 Signaling 6.67E-01 1.67E- CXCL11,CCL2,MAPK3,MAPK10,
01 PIK3R5,MAPK9,CXCL1 ,ΜΑΡΚΙ 3,
PIK3R2,JAK2,IL6,IL17RA Mitochondrial 6.65E-01 1.52E- ATP5H,NDUFA9,UCP2,PRDX5, Dysfunction 01 CPT1B,GLRX2,NDUFB5,SURF1,
BACE1,MAPK9,GPX7,APP,BCL2, VPS9D 1 ,SOD2,NDUFS8,GPD2, APH 1 A,NDUFA6,C ΑΤ,ΜΑΡΚΙ 0, SDHD,CYB5A,ACO 1 ,NDUFB2,PINK1
ErbB Signaling 6.63E-01 1.63E- GRB2,PIK3R5,PLCG1,MAPK9,
01 MAPK13,PRKCZ,PAK1 ,MTOR, PRKCI,CDC42,MAPK3,MAPK10, PIK3R2,PRKCB
Chronic Myeloid 6.63E-01 1.61E- TFDP1,GRB2,ABL1,PIK3R5, Leukemia Signaling 01 CDK6,IKBKE,CRK,RBL1,CCND 1 ,
IKBKB,RB 1,MAPK3,E2F5,PIK3R2, E2F2
Salvage Pathways of 6.63E-01 FAM20B,CMPK2,SGK1,UPP1,
Pyrimidine 01 CDK6,MAPK9,GRK5,LIMK2,
Ribonucleotides IRAKI , APOBEC3 Α,ΡΑΚΙ , ARAF,
MAPK3,APOBEC3H,CDK2
Dermatan Sulfate 6.57E-01 1.78E- CHST2,SULT 1 C2,SULT 1 A 1 ,NDST2, Biosynthesis (Late 01 CHST13,HS3ST3A1,CHST15,DSE Stages)
Role of NFAT in Cardiac 6.51E-01 1.51E- PIK3R5,IL6,MAPK13,GNG7,PRKCZ, Hypertrophy 01 GNB4,PLCD3,CAMK2D,GNG11,
MAPK3,PLCB 1 ,PIK3R2,GNG5, CAMK2B,SRC,GRB2,ADCY3, MAPK9,PLCG 1 ,GNG 10,PRKCI, ADC Y 1 JTPR3 ,ΜΑΡΚΙ 0,PRKAG2, ADCY7,PRKCB
DNA damage -induced 6.48E-01 2.11E- CCNE2,CCNE 1 ,BRC A 1 ,CDK2 14-3-3σ Signaling 01
NAD Biosynthesis from 6.45E-01 2.86E- ABL1,NMNAT3
2-amino-3- 01
carboxymuconate
Semialdehyde
Phosphatidylcholine 6.45E-01 2.86E- CHPT1,PHKA1
Biosynthesis I 01
Adenine and Adenosine 6.45E-01 2.86E- ADA,ADAT3
Salvage III 01
GDP-glucose 6.45E-01 2.86E- HK1,PGM1
Biosynthesis 01
Cytotoxic T 6.45E-01 1.88E- CASP6,HLA-A,HLA-C,
Lymphocyte -mediated 01 FCER1G,BID,BCL2
Apoptosis of Target
Cells
Mitotic Roles of Polo- 6.41E-01 1.67E- HSP90B 1,ESPL1,HSP90AB 1, Like Kinase 01 PPP2R4,CDC7,PKMYT1,FBX05,
ANAPC 13,STAG2,PPP2R5 A, CDC25A
Cholecystokinin/Gastrin- 6.4E-01 1.58E- SRCJL1 A,GRB2,GNA 12,MAPK9, mediated Signaling 01 PRKCZ,PRKCLIL1RN,MAPK3,
ITPR3,RH0U,MAPK10,PLCB 1 , IL1B,FNBP1,PRKCB
NF-KB Activation by 6.39E-01 1.64E- ITGB2,IKB KB ,PRKCI,M APK3 , Viruses 01 NFKB IE,PIK3R5 ,ITG A5 ,1KB KE, PIK3R2,PR CZ,TNFRSF14,PRKCB
324 Ceramide Signaling 6.38E-01 1.62E- S1PR3,CTSD,S1PR5,PPP2R4,
01 TNFRSF1A,MAPK3,SPHK1,
PIK3R5,PIK3R2,TNFRSF1B, PRKCZ,PPP2R5A,BCL2
325 FAK Signaling 6.38E-01 1.61E- SRC,GRB2,PIK3R5,PLCG1,ITGA5,
01 CRK,PAK1,TLN2,WAS,MAPK3, PIK3R2,CAPN7,VCL,TNS1
326 ERK/MAPK Signaling 6.38E-01 1.5E- YWHAH,DUSP6,PIK3R5,CRK,
01 NFATC1,YWHAQ,PAK1,PPP1R12A, PPP1R7,MAPK3,PIK3R2,STAT1, SRC,GRB2,ITGA5,PLCG1,RPS6KA5, STAT3,PPP2R5A,PLA2G4A,PRKCI, TLN2,ARAF,PPP2R4,PRKAG2, RPS6KA1,ELK3,PRKCB
327 Role of IL-17A in 6.36E-01 2.31E- S100A9,CXCL1,IL17RA
Psoriasis 01
328 Glycogen Degradation 6.36E-01 2.31E- PGM 1 ,P YGB ,ΤΥΜΡ
III 01
329 Mevalonate Pathway I 6.36E-01 2.3 IE- M VD, AC AT2, AC AT 1
01
330 D-myo-inositol (1,4,5)- 6.2E-01 1.92E- PLCD3,PI4K2A,PIP5K1C,
Trisphosphate 01 PLCGLPLCBl
Biosynthesis
331 Semaphorin Signaling in 6.17E-01 1.7E- MET,SEMA3 Α,ΡΑΚΙ ,SEMA4D,
Neurons 01 MAPK3,RH0U,LIMK2,FNBP1,
NRP1
332 Asparagine Degradation 6.16E-01 5E-01 ASRGL1
1
333 Dolichol and Dolichyl 6.16E-01 5E-01 DHDDS
Phosphate Biosynthesis
334 Epoxysqualene 6.16E-01 5E-01 SQLE
Biosynthesis
335 β-alanine Degradation I 6.16E-01 5E-01 ALDH6A1
336 All-trans-decaprenyl 6.16E-01 5E-01 PDSS1
Diphosphate
Biosynthesis
337 Proline Degradation 6.16E-01 5E-01 ALDH4A1
338 Choline Degradation I 6.16E-01 5E-01 ALDH7A1
339 Alanine Degradation III 6.16E-01 5E-01 GPT2
340 Alanine Biosynthesis II 6.16E-01 5E-01 GPT2
341 4-hydroxyproline 6.16E-01 5E-01 ALDH4A1
Degradation I
342 Glycine Degradation 6.16E-01 5E-01 GAMT
(Creatine Biosynthesis)
343 Threonine Degradation II 6.16E-01 5E-01 GCAT
344 Putrescine Biosynthesis 6.16E-01 5E-01 ODC1
III
345 Glutamine Degradation I 6.16E-01 5E-01 GLS Epithelial Adherens 5.97E-01 1.51 E- VAV2,MYH 10,SRC,TCF4,TGFBR3, Junction Signaling 01 FGFRl ,TUBG1 ,ARPC5,TUB A4A,
BMPR2,MYH7,CRK,ACVR1B, MET,CDH2,AGGF1 ,WAS,CDC42, ARPC2,SSX2IP,VCL,PVRL2
347 Purine Nucleotides 5.95E-01 2E-01 NT5C3A,IMPDH2,ADA,ADAT3
Degradation II (Aerobic)
348 GDNF Family Ligand- 5.86E-01 1.62E- GRB2,CDC42,MAPK3,ITPR3,
Receptor Interactions 01 MAPK10,PIK3R5,PLCG1,MAPK9,
GFRA2,DOK3,PIK3R2
T Cell Recept( 5.71E-01 1.55E- VAV2,GRB2,PIK3R5,PLCG1, Signaling 01 1KB KE,CTLA4,NFATC 1 ,PTPRC,
BTK,IKBKB,CBL,VAV3,MAPK3,
PIK3R2,LCP2
TWEAK Signaling 5.65E-01 1.76E- C ASP6JKB KB ,TRAF3 ,
01 NFKBIE,BID,IKBKE
Synaptic Long Term 5.62E-01 1.51E- PLCG 1 ,PRKCZ,GRINA,GRIN3A, Potentiation 01 PLCD3,CAMK2D,PRKCI,GNA15,
PPP1R12A,PPP1R7,MAPK3,
ADC Y 1 ,ITPR3,PRKAG2,PLCB 1 ,
RPS6KA1,PRKCB,CAMK2B
352 MIF Regulation of Innate 5.6E-01 1.71E- PLA2G4A,LY96,MAPK3,NFKBIE, Immunity 01 M APK10,CD 14,MAPK9
353 Agrin Interactions at 5.6E-01 1.59E- ITGB2,SRC,PAK1,CDC42,MAPK3, Neuromuscular Junction 01 LAMA2,LAMB1,MAPK10,ITGA5,
MAPK9,DAG1
354 Primary 5.58E-01 1.67E- IL7R,PTPRC,BTK,RFXAP,
Immunodeficiency 01 CUT A, AD A,T AP 1 ,UNG
Signaling
355 Sphingosine and 5.57E-01 2.5E- SGPP2,ASAH1
Sphingosine- 1 -phosphate 01
Metabolism
356 Glucose and Glucose- 1- 5.57E-01 2.5E- HK1,PGM1
phosphate Degradation 01
357 Citrulline Biosynthesis 5.57E-01 2.5E- GLS,OAT
01
358 Purine Ribonucleosides 5.57E-01 2.5E- ADA,ADAT3
Degradation to Ribose-1- 01
phosphate
359 Integrin Signaling 5.54E-01 1.45E- MPRIP,ARPC5,PIK3R5,ABL1,
01 CRK,ITGB7,ITGAE,PAK1 ,ΡΡΡΙ Rl 2A, MAPK3,RHOU,PFN2,VCL,PIK3R2, MYL12A,SRC,GRB2,ITGA5,PLCG1, GIT 1 ,ITGB2,WIPF1 ,TLN2,ITGAM, WAS,LIMS 1 ,CDC42, ARPC2, CAPN7,FNBP1
360 ILK Signaling 5.53E-01 1.46E- MYH10,FLNB,MUC1,PIK3R5,
01 HIF1A,CCND1,ITGB7,MT0R,
PPP1R12A,MAPK3,RH0U,VCL, PIK3R2,TMSB 10 TMSB4X,
TNFRSF1A,FERMT2,MAPK9, MYH7,RPS6KA5,PPP2R5A,ITGB2, CDC42,LIMS 1 ,PPP2R4,MAPK10, FNBP1,MMP9 361 Adipogenesis pathway 5.52E-01 1.49E- ARNTL,TNFRSF 1 A,FZD3 ,FGFR 1 ,
01 NR2F2,RBBP7,PPIP5K1,BMPR2, HIF1A,BSCL2,CTNNBIP1,FGFR3, EGR2,FZD4,EZH2,FZD6,KLF3, RPS6KA 1 ,PER2,GTF2H3
Regulation of Actin- 5.45E-01 1.54E- PAK1,WIPF1,MPRIP,PPP1R12A, based Motility by Rho 01 WAS,PIP5K1C,CDC42,ARPC2,
ARPC5,RHOU,PFN2,ITGA5, FNB P1,MYL12A
363 CREB Signaling in 5.43E-01 1.46E- PIK3R5,PRKCZ,GNG7,PLCD3,
Neurons 01 GNB4,GNG11,CAMK2D,GNA15,
MAPK3,PLCB 1 ,PIK3R2,GNG5, C AMK2B ,GRB2,GNA 12, ADC Y3 , PLCG1,GNG10,PRKCI,ITPR3, ADC Y 1 ,PRKAG2,RPS6KA1 , ADCY7,PRKCB
364 CDK5 Signaling 5.29E-01 1.52E- ADC Y3 , AB L 1 ,M APK9,M APK13 ,
01 PPP2R5A,CDK5R1,PPP1R12A,
PPP 1 R7,PPP2R4,M APK3 , ADC Y 1 , PRKAG2,MAPK10,LAMB 1,ADCY7
365 Sperm Motility 5.24E-01 1.49E- SLC 16A 10/TWFl ,SLC 12A2,PLCG 1 ,
01 PDE4B,CNGA1,PLA2G7,PRKCZ, PLCD3,PLA2G4A,PRKCI,ITPR3, PDE 1 B ,GUCY 1 A2,PRKAG2,PLCB 1 , CATSPER1,PRKCB
366 VEGF Signaling 5.24E-01 1.52E- SH2D2A,SRC,PTPN6,GRB2,PIK3R5,
01 PLCG1,HIF1A,N0S3,BCL2,MAPK3, PIK3R2,VCL,EIF1AY,PRKCB
367 FGF Signaling 5.19E-01 1.53E- PTPN6,GRB2,FGFR1,PIK3R5,PLCG1,
01 RPS6KA5,CRK,STAT3,MAPK13, MET,FGFR3 ,M APK3 ,PIK3R2
The Visual Cycle 5.15E-01 2E-01 DHRS 3 ,DHRS9,RDH5
NGF Signaling 5.14E-01 1.5E- GRB2,PIK3R5,PLCG1,MAPK9,
01 RPS6KA5,IKBKE,CRK,BAX,
PRKCZJKB KB ,CDC42,MAPK3 , MAPK10,RPS6KA2,PIK3R2, RPS6KA1
370 PEDF Signaling 5.11E-01 1.55E- IKBKB,TCF4,SOD2,MAPK3,
01 NFKB IE,PIK3R5 ,ΙΚΒ ΚΕ,Μ APK13 , PIK3R2,PNPLA2,BCL2
371 Glutamate Receptor 5.03E-01 1.58E- GNG11,H0MER2,GLS,SLC1A3, Signaling 01 SLC38A1,GNG5,GNG7,GRINA,
GRIN3A
372 Pyrimidine 5.01E-01 1.82E- TYMS,CMPK2,RRM2,RRM 1
Deoxyribonucleotides De 01
Novo Biosynthesis I
373 TNFR2 Signaling 4.96E-01 1.72E- IKBKB,NFKBIE,IKBKE,TBK1,
01 TNFRSF1B
374 autophagy 4.96E-01 1.67E- MTOR,LAMP2,VPS18,ATG10,
01 VPS33A,BCL2 375 G-Protein Coupled 4.94E-01 1.41E- HTR2B,DUSP6,NFKBIE,PIK3R5,
Receptor Signaling 01 AD0RA3,RGS12,MPPE1,0PRL1,
HRH 1 ,1KB KB ,C AMK2D,GNA 15 , MAPK3,TDP2,PLCB 1 ,PIK3R2, CAMK2B,SRC,GRB2,CNR1, ADCY3,FPR2,IKBKE,PDE4B, STAT3,S 1 PR3.VIPR 1 ,RAP 1 GAP, ADC Y 1 ,PDE 1 B ,PRKAG2,PDE5 A, PTGER2,RPS6KA 1 , ADC Y7,PRKCB
376 Regulation of IL-2 4.93E-01 1.52E- VAV2,IKBKB,CD80,GRB2,VAV3,
Expression in Activated 01 M APK3 ,NFKB ΙΕ,Μ APK10,PLCG 1 , and Anergic T MAPK9,IKBKE,NFATC 1
Lymphocytes
377 Sucrose Degradation V 4.84E-01 2.22E- GALM,TKFC
(Mammalian) 01
378 Heme Biosynthesis II 4.84E-01 2.22E- UROS,ALAD
01
379 Heparan Sulfate 4.73E-01 1.57E- CHST2,SULT 1 C2,SULT 1 A 1 ,
Biosynthesis (Late 01 NDST2,CHST13,EXTL2,
Stages) HS3ST3A1.CHST15
380 Amyloid Processing 4.73E-01 1.57E- APH 1 A,M APK3 ,PRKAG2,
01 B ACE 1 ,ΜΑΡΚΙ 3,C APN7,
CDK5R1,APP
381 Diphth amide 4.68E-01 3.33E- DPH5
Biosynthesis 01
382 Trehalose Degradation II 4.68E-01 3.33E- HK1
(Trehalase) 01
383 NADH Repair 4.68E-01 3.33E- APOA1BP
01
384 Methylglyoxal 4.68E-01 3.33E- HAGH
Degradation I 01
385 1 ,25 -dihydroxy vitamin 4.68E-01 3.33E- CYP27B1
D3 Biosynthesis 01
386 Glutathione Biosynthesis 4.68E-01 3.33E- GSS
01
387 Tetr hydrobiopterin 4.68E-01 3.33E- GCH1
Biosynthesis I 01
388 Thyroid Hormone 4.68E-01 3.33E- CTSD
Biosynthesis 01
389 Glycerol-3-phosphate 4.68E-01 3.33E- GPD2
Shuttle 01
390 Tetrahydrobiopterin 4.68E-01 3.33E- GCH1
Biosynthesis II 01
391 Tyrosine Biosynthesis IV 4.68E-01 3.33E- PCBD2
01
392 4-aminobutyrate 4.68E-01 3.33E- ALDH5A1
Degradation I 01
393 L-serine Degradation 4.68E-01 3.33E- SDS
01
394 N-acetylglucosamine 4.68E-01 3.33E- GNPDA2
Degradation I 01 Serotonin Receptor 4.68E-01 1.59E- GCH 1 ,HTR2B , ADC Y 1 , ADC Y3 , Signaling 01 SLC18A1,ADCY7,IL4I1
CDP-diacylglycerol 4.65E-01 1.88E- AGPAT4,AGPAT3,CDS2
Biosynthesis I 01
Wnt/ -catenin Signaling 4.63E-01 1.42E- SRC,TCF4,MMP7,SFRP2,
01 CSNK1G1,APPL2,FZD3,PPARD,
CSNK1G2,TGFBR3,BMPR2,
SOX 13,CCND 1 ,AC VRl B,PPP2R5 A,
CDH2,DVL2,FZD4,PPP2R4,FZD6,
MAP4K1 ,SOX 18,SFRP 1 ,ΡΙΝΙ
TCA Cycle II 4.6E-01 1.74E- SUCLG 1 ,SDHD,MDH 1 , ACO 1 (Eukaryotic) 01
Angiopoietin Signalin 4.6E-01 1.52E- IKBKB,TNIP1,PAK1,GRB2,
01 NFKBIE,PIK3R5,IKBKE,CRK,
PIK3R2,NOS3
RANK Signaling 4.58E-01 1.48E- SRC,NFKBIE,PIK3R5,MAPK9, Osteoclasts 01 1KB ΚΕ,ΜΑΡΚΙ 3,NFATC 1 ,1KB KB,
CBL,MAPK3,MAPK10,PIK3R2, TRAF5
CD27 Signaling in 4.47E-01 1.54E- 1KB KB , SIVA 1 ,NFKB ΙΕ,Μ APK10, Lymphocytes 01 MAPK9,BID,IKBKE,TRAF5
FXR/RXR Activation 4.4E-01 1.43E- AP0E,MLXIPL,IL1A,AP0M,
01 AP0A4,C3,CYP27A1,NR1H3, MAPK9,APOC2,VLDLR,APOLl , IL1RN,CYP19A1,MAPK10, AP0C1,IL1B,RXRA
Serotonin Degradation 4.37E-01 1.49E- ALDH4A 1 , ALDH2, AKR 1 A 1 ,
01 ALDH1A1 ,DHRS9,ALDH3A2, SULT 1 A 1 ,PECR, ALDH7 A 1 ,IL411 ErbB4 Signaling 4.3E-01 1.5E- PRKCI,GRB2, APH 1 Α,Μ APK3 ,
01 PIK3R5,PLCG1,PIK3R2,PRKCZ, PRKCB
Tumoricidal Function of 4.23E-01 1.67E- M6PR,CASP6,BID,BAX
Hepatic Natural Killer 01
Cells
Superpathway of D-myo- 4.23E-01 1.67E- IMPA2,ITPKA,OCRL,INPP5D inositol (1,4,5)- 01
trisphosphate
Metabolism
mTOR Signaling 4.23E-01 1.39E- TSC 1 ,RPS 18,PIK3R5,FKBP 1 A,
01 HIF1 A,PRKCZ,MTOR,RPS 13, MAPK3,RHOU,RPS6KA2,PIK3R2, RPS3, AKT 1 S 1 ,EIF3H,RPS6KA5, MLST8,PPP2R5A,PRKCI,PPP2R4, RPS27L,PRKAG2,RPS6KA 1 ,EIF3L, FNB PI, PRKCB
Embryonic Stem Cell 4.23E-01 2E-01 MESP1,SP4
Differentiation into
Cardiac Lineages
Ketogenesis 4.23E-01 2E-01 ACAT2,ACAT1
Calcium Transport I 4.23E-01 2E-01 ATP2A3,ATP2A2 411 Dolichyl- 4.23E-01 2E-01 ALG5,ALG6
diphosphooligosaccharid
e Biosynthesis
412 Adenosine Nucleotides 4.2E-01 1.76E- NT5C3A,ADA,ADAT3
Degradation II 01
413 Superpathway of 4.2E-01 1.76E- MVD,ACAT2,ACAT1
Geranylgeranyldiphosph 01
ate Biosynthesis I (via
Mevalonate)
414 Remodeling of Epithelial 4.16E-01 1.47E- MET,SRC,RAB5C,ARPC2,ARPC5, Adherens Junctions 01 TUBG1,TUBA4A,DNM3,VCL,
MAPRE2
415 Role of Oct4 in 4.15E-01 1.52E- CASP6,RB 1,SPP1,BMI1,
Mammalian Embryonic 01 NR2F2,BRCA1,ASH2L
Stem Cell Pluripotency
416 RhoGDI Signaling 4.1E-01 1.39E- SRC,GNA12,ARPC5,ITGA5,
01 LIMK2,GNG7,GNG 10,GNB4, PAK1,CDH2,GNG11,PPP1R12A, GNA 15 ,PIP5 Kl C,CDC42,EZR, ARPC2,ARHGEF16,RHOU, ARHGEF3 ,GNG5 , ARHGEF 10, FNB P 1 ,M YL 12 A
417 VEGF Family Ligand- 4.05E-01 1.45E- PLA2G4A,PRKCI,GRB2,MAPK3, Receptor Interactions 01 PIK3R5,PLCG1,PIK3R2,N0S3,
PRKCZ,NRP1,PRKCB
418 Role of MAPK Signaling 3.96E-01 1.45E- PLA2G4A,CCL2,MAPK3,MAPK10, in the Pathogenesis of 01 MAPK9,MAPK13,B AX,CCL5, Influenza PLA2G7,BCL2
419 Chondroitin Sulfate 3.9E-01 1.49E- CHST2,SULT 1 C2,SULT 1 A 1 ,
Biosynthesis (Late 01 NDST2,CHST13,HS3ST3A1, Stages) CHST15
420 Gluconeogenesis I 3.89E-01 1.6E- PG AM 1 ,ME3 ,ME2,MDH 1
01
421 RhoA Signaling 3.87E-01 1.39E- SEPT5,MPRIP,SEPT4,GNA 12,
01 ARPC5,CDC42EP4,LIMK2,
SEPT11,LPAR6,RAPGEF2,
PPP1R12A,LPAR2,PIP5K1C,
EZR, ARPC2,PFN2,M YL 12A
422 Neuroprotective Role of 3.8E-01 1.5E- HLA-G,HLA-A,HLA-C,
THOP1 in Alzheimer's 01 PRKAG2,MMP9,APP
Disease
423 Phosphatidylglycerol 3.8E-01 1.67E- AGPAT4,AGPAT3,CDS2
Biosynthesis II (Non- 01
plastidic)
424 D-myo-inositol (1,4,5)- 3.8E-01 1.67E- IMPA2,OCRL,INPP5D
trisphosphate 01
Degradation
425 Uracil Degradation II 3.71E-01 2.5E- DPYS
(Reductive) 01
426 Spermine and 3.71E-01 2.5E- PAOX
Spermidine Degradation 01
I 427 Ascorbate Recycling 3.71E-01 2.5E- GSTOl
(Cytosolic) 01
428 Glutathione Redox 3.71E-01 2.5E- TXNDC12
Reactions II 01
429 Myo-inositol 3.71E-01 2.5E- IMPA2
Biosynthesis 01
430 Thymine Degradation 3.71E-01 2.5E- DPYS
01
431 Proline Biosynthesis I 3.71E-01 2.5E- PYCR2
01
432 Melatonin Degradation II 3.71E-01 2.5E- IL4I1
01
433 Phenylalanine 3.71E-01 2.5E- PCBD2
Degradation I (Aerobic) 01
434 Dopamine-DARPP32 3.71E-01 1.37E- CSNK1G1,CSNK1G2,ADCY3,
Feedback in cAMP 01 ATP2A3 ,PLCG 1 ,ATP2A2,PPP2R5 A,
Signaling PRKCZ,GRIN3A,GRINA,PLCD3,
PRKCI,PPP 1 Rl 2A,PPP2R4,PPP 1 R7, ADC Y 1 ,ITPR3 ,GUC Y 1 A2,PRKAG2, PLCB 1,ADCY7,PRKCB
435 Circadian Rhythm 3.7E-01 1.52E- ARNTL,CRY 1 ,PER2,GRINA,GRIN3A
Signaling 01
436 MIF-mediated 3.7E-01 1.52E- PLA2G4A,LY96,MAPK3,NFKBIE,CD 14
Glucocorticoid 01
Regulation
437 Retinol Biosynthesis 3.7E-01 1.52E- CEL,DHRS3,DHRS9,LIPG,PNPLA2
01
438 Dopamine Receptor 3.68E-01 1.41E- GCH1,PPP1R12A,PPP1R7,PPP2R4,
Signaling 01 ADC Y 1 , ADC Y3,PRKAG2,SLC 18 A 1 ,
ADCY7,PPP2R5A,IL4I1
439 PCP pathway 3.67E-01 1.43E- DVL2,FZD4,FZD3,EFNB 1 ,D A AM 1 ,
01 MAPK10,FZD6,PFN2,MAPK9
440 Renal Cell Carcinoma 3.58E-01 1.41E- ΜΕΤ,ΡΑΚΙ ,GRB2,CUL2,CDC42,
Signaling 01 MAPK3,PIK3R5,CRK,HIF1A,
PIK3R2
441 Wnt/Ca+ pathway 3.57E-01 1.43E- PLCD3,DVL2,FZD4,FZD3,FZD6,
01 PLCG 1 ,PLCB 1 ,NFATC 1
442 Insulin Receptor 3.53E-01 1.36E- TSC 1 ,SGK1 ,GRB2,TRIP 10,
Signaling 01 PIK3R5 ,CRK,JAK2,OCRL,
INPP5D,PRKCZ,MTOR,PRKCI, CB L,PPP 1 R 12 Α,ΡΡΡΙ R7,MAPK3, PRKAG2,PIK3R2
443 lD-myo-inositol 3.44E-01 1.58E- ITPKA,OCRL,INPP5D
Hexakisphosphate 01
Biosynthesis II
(Mammalian)
444 D-myo-inositol (1,3,4)- 3.44E-01 1.58E- ITPKA,OCRL,INPP5D
trisphosphate 01
Biosynthesis
445 IL-9 Signaling 3.43E-01 1.47E- PIK3R5,BCL3,STAT3,PIK3R2,STAT1
01
446 Mouse Embryonic Stem 3.38E-01 1.37E- TCF4,GRB2,FZD3,PIK3R5,
Cell Pluripotency 01 BMPR2,STAT3,MAPK13,JAK2, DVL2,FZD4,MAPK3,FZD6,
PIK3R2
Hypoxia Signaling in the 3.3E-01 1.38E- HSP90B1,UBE2J1,HSP90AB 1, Cardiovascular System 01 NFKBIE,UBE2V1,UBE2E3,
HIF1A,N0S3,UBE2F
Corticotropin Releasing 3.28E-01 1.35E- CNR1,ADCY3,ARPC5,PLCG1, Hormone Signaling 01 MAPK13,NOS3,PRKCZ,PRKCI,
MAPK3,ITPR3,ADCY1,GUCY1A2, PRKAG2,ADCY7,PRKCB
449 Cleavage and 3.26E-01 1.67E- NUDT21,CPSF4
Polyadenylation of Pre- 01
mRNA
450 Nucleotide Excision 3.19E-01 1.43E- RPA3,XPC,RPA1,GTF2H3,RPA2 Repair Pathway 01
451 Heparan Sulfate 3.18E-01 1.38E- CHST2,SULT1C2,SULT1A1,
Biosynthesis 01 NDST2,CHST13,EXTL2,
HS3ST3A1.CHST15
452 Dermatan Sulfate 3.18E-01 1.38E- CHST2,SULT1C2,SULT1A1,
Biosynthesis 01 NDST2,CHST13,HS3ST3A1,
CHST15,DSE
453 DNA Methylation and 3.11E-01 1.5E- MBD3,RBBP7,DNMT1
Transcriptional 01
Repression Signaling
454 Tight Junction Signalin; 3.03E-01 1.32E- M YH 10,CLDN 15 ,TNFRSF 1 A,
01 RAB13,MPP5,MYH7,CASK,
PPP2R5 A,CPSF4,PRKCZ,SMURF1 , NSF,PRKCI,PPP2R4,CDC42, NUDT21 ,PRKAG2,S AFB , VCL, TNFRSF1B,NAPA,PVRL2
455 Creatine-phosphate 3.01E-01 2E-01 CKM
Biosynthesis
456 Tetrahydrofolate Salvage 3.01E-01 2E-01 GART
from 5,10- methenyltetrahydrofolate
457 CMP-N- 3.01E-01 2E-01 NAGK
acetylneuraminate
Biosynthesis I
(Eukaryotes)
458 Eumelanin Biosynthesis 3.01E-01 2E-01 DDT
459 Citrulline-Nitric Oxide 3.01E-01 2E-01 NOS3
Cycle
460 Glutamate Degradation 3.01E-01 2E-01 ALDH5A1
III (via 4-aminobutyrate)
461 Fatty Acid Activation 2.87E-01 1.54E- ACSL4,SLC27A3
01
462 Choline Biosynthesis III 2.87E-01 1.54E- CHPT1,PHKA1
01
463 NAD Phosphorylation 2.87E-01 1.54E- ACP2,NADK
and Dephosphorylation 01
464 Regulation of eIF4 and 2.79E-01 1.3E- EIF4EBP2,EIF3H,GRB2,RPS18, p70S6K Signaling 01 PI 3R5,ITGA5,MAPK13,PPP2R5A,
PR CZ,MTOR,RPS 13,PPP2R4, MAPK3,AG03,RPS27L,PIK3R2,
RPS3,EIF3L,EIF1AY
465 Glutathione -mediated 2.78E-01 1.38E- GSTM2,GSTA4,GGH,GSTO 1
Detoxification 01
466 BMP signaling pathway 2.77E-01 1.32E- FST,GRB2,MAPK3,BMP8B,MAPK10,
01 PRKAG2,BMPR2,MAPK9,MAPK13, SMURF1
467 Role of pl4/pl9ARF in 2.56E-01 1.33E- RB1,PIK3R5,TTF1,PI 3R2
Tumor Suppression 01
468 Androgen Biosynthesis 2.54E-01 1.43E- SRD5A3,SRD5A1
01
469 Urate 2.54E-01 1.43E- NT5C3AJMPDH2
Biosynthesis/Inosine 5'- 01
phosphate Degradation
470 Arginine Biosynthesis IV 2.48E-01 1.67E- OAT
01
471 Urea Cycle 2.48E-01 1.67E- CPS1
01
472 Glycine Cleavage 2.48E-01 1.67E- AMT
Complex 01
473 Selenocysteine 2.48E-01 1.67E- PSTK
Biosynthesis II (Archaea 01
and Eukaryotes)
474 UDP-N-acetyl-D- 2.48E-01 1.67E- UAP1
glucosamine 01
Biosynthesis II
475 Ceramide Degradation 2.48E-01 1.67E- ASAH1
01
476 Rapoport-Luebering 2.48E-01 1.67E- PGAM1
Glycolytic Shunt 01
477 NAD Biosynthesis III 2.48E-01 1.67E- NMNAT3
01
478 nNOS Signaling in 2.25E-01 1.33E- RYR1.DAG1
Skeletal Muscle Cells 01
479 Leukotriene Biosynthesis 2.25E-01 1.33E- LTA4H,LTC4S
01
480 γ-glutamyl Cycle 2.25E-01 1.33E- GGCT,GSS
01
481 Acetyl-CoA Biosynthesis 2.07E-01 1.43E- PDHB
I (Pyruvate 01
Dehydrogenase
Complex)
482 NAD Salvage Pathway 2.07E-01 1.43E- NMNAT3
III 01
483 Inositol Pyrophosphates 2.07E-01 1.43E- PPIP5K1
Biosynthesis 01
[0087] Table 6. Table of antibodies used for mass cytometry analysis listing metal conjugate, antibody clone name and supplier of each marker. Isotope Tag Antibody Clone Company
Qdot 655 CD19 6D5 Invitrogen (Cdl l2/114)
Rh-103 Barcode (1:300)
Pd-104 Barcode (1:2000)
Pd-105 Barcode (1: 100)
Pd-106 Barcode (1: 1000)
Pd-108 Barcode (1: 1000)
Pd-110 Barcode (1:250)
In- 113 Barcode (1:500)
La- 139 CD45 30-F11 Biolegend
Pr-141 CD43 S l l Biolegend
Nd-142 MHCII Y-3P BioXCell
Nd-143 B220 RA3-3A1/6.1 BioXCell
Nd-144 CDl la FD441 BioXCell
Nd-145 Ly6GC RB6-8C5 BD Biosciences
Nd-146 CD8a 53-6.7 BD Biosciences
Sm-147 Ly6G 1A8 BD Biosciences
Nd-148 Ly6c HK1.4 Biolegend
Sm-149 CD4 H129.19 BD Biosciences
Nd-150 IgD l l-26c.2a BD Biosciences
Eu-151 CD62L MEL- 14 Biolegend
Sm-152 CDl lc N418 Biolegend
Eu-153 CDl lb Ml/70 BD Biosciences
Sm-154 CD3 145-2C11 BD Biosciences
Gd-155 CD86 GL1 BD Biosciences
Gd-156 BST2 PDCA-1 Purified in house
Gd-157 CD27 LG.7F9 eBioscience
Gd-158 CD80 1G10/B7 BD Biosciences
Tb-159 F4/80 C1:A3-1 AbD Serotec
Gd-160 FcERla MAR-1 eBioscience Dy-161 CD25 PC61 Biolegend
Dy-162 PDL-1 10F.9G2 Biolegend
Dy-163 PDL-2 TY25 Biolegend
Dy-164 CD103 2E7 Biolegend
Ho- 165 CD64 X54-5/7.1 Biolegend
Er-166 CD48 HM48-1 Biolegend
Er-167 CD49b DX5 Biolegend
Er-168 CD44 IM7 Biolegend
Tm-169 IgM RMM-1 Biolegend
Er-170 CD38 90 Biolegend
Yb-171 MerTK (SAV) Mer-Biotin accession R&D systems number: 60805
Yb-172 Ly6A/E (Sca-l) D7 BD Biosciences
Yb-173 CD172 P84 BD Biosciences
Yb-174 CD24 Ml/69 Biolegend
Lu-175 Siglec-F E50-2440 BD Biosciences
Yb-176 CD90 T24/31 BioXCell
Ir-191/193 DNA Fluidigm
Pt-195 Cisplatin (viability Sigma- Aldrich stain)
[0088] Table 7. Sequences of primers used in this study.
Name Sequences of primers 5' to 3'
hSIRTIF TGGCACAGATCCTCGAACAA
hSIRTIR TGCCACAGTGTCATATCATCCA
hGAPDHF GCAAATTCCATGGCACCGT
hGAPDHR TCGCCCCACTTGATTTTGG
hILlbF TTCGACACATGGGATAACGAGG
hILlbR TTTTTGCTGTGAGTCCCGGAG
hTNFaF CTGCTGCACTTTGGAGTGAT hTNFaR AGATGATCTGACTGCCTGGG
ML6F ACCCCCAATAAATATAGGACTGGA hIL6R GTTCATAGCTGGGCTCCTGG hMCPlF TCGCCTCCAGCATGAAAGTC hMCPIR GAAGAAGAGGGGGCCTTACC hRelAF TGCTTGGCAACAGCACAGA hRelAR AGCTGCTGAAACTCGGAGTTGT hTNFaF CHIP GCTTCCTCCAGATGAGCTT hTNFaR CHIP TGCTGTCCTTGCTGAGGGA hILlbF CHIP TCCCTCCCTTAGTGCCAACTATGT
ILlbR CHIP ACAGTCTCCACAGTTCTGCCATGT
IL6F CHIP GCTAGCCTCAATGACGACCT
IL6R CHIP GCCTCAGACATCTCCAGTCC
MCP-1 CHIP GCTTCCCTTTCCTACTTCCTG
MCP-1 CHIP TGCTGTCTCTGCCTCTTATTG mTNFaF CCACGTCGTAGCAAACCACC mTNFaR CCTTGTCCCTTGAAGAGAACC mILlbF TGCCACCTTTTGACAGTGATG mILlbR TGATGTGCTGCTGCGAGATT mIFNgF AGCAAGGCGAAAAAGGATGC mIFNgR TCATTGAATGCTTGGCGCTG mSIRTIF TGATTGGCACCGATCCTCG mSIRTIR CCACAGCGTCATATCATCCAG mRelAF TGTGGAGATCATCGAACAGCCG mRelAR TTCCTGGTCCTGTGTAGCCATTGAT mGAPDHF TCGTCCCGTAGACAAAATGG mGAPDHR TTGAGGTCAATGAAGGGGTC

Claims

A method of preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof, wherein the method comprises administration of a compound which enhances activity of an NAD+-dependent deacetylase.
The method of claim 1, wherein the compound is a sirtuin enhancer.
The method of any of the preceding claims, wherein the NAD+-dependent deacetylase is selected from the group consisting of sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7, derivatives, homologues and combinations thereof.
The method of any of the preceding claims, wherein the compound is selected from the group consisting of N-[2-[3-(piperazin-l-ylmethyl)imidazo[2,l-b][l,3]thiazol-6- yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N-cyclopentyl-2-diazenyl-l-(3- methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4- phenyl-l,4-dihydro-3,5-pyridinedicarboxylate (BML278); and salts and/or derivatives thereof.
The method of claim 4, wherein the compound is N-[2-[3-(piperazin-l- ylmethyl)imidazo [2, 1 -b] [ 1 ,3 ] thiazol-6-yl]phenyl] quinoxaline-2-carboxamide
(SRT1720) or a derivative thereof.
The method of any of the preceding claims, wherein the compound is administered at a concentration ranging from between about 1 mg/kg to about 2000 mg/kg (2 g/kg) of the body weight of the patient.
The method of claim 6, wherein the compound is administered at a concentration of 10 mg/kg of the body weight of the patient.
8. The method of any of the preceding claims, wherein the intracellular mycobacterium is selected from the group consisting of a drug-resistant mycobacterium, a multidrug- resistant mycobacterium and an extensively drug-resistant mycobacterium. 9. The method of any of the preceding claims, wherein the mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium africanum, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium leprae, Mycobacterium avium, Mycobacterium paratuberculosis and Mycobacterium pinnipedii.
10. The method of any of the preceding claims, wherein the compound is used in a combination therapy. 11. The method of claim 10, wherein the combination therapy comprises an antituberculosis drug.
12. The method of claim 11, wherein the anti-tuberculosis drug is selected from the group consisting of amikacin, aminosalicylic acid, bedaquiline, capreomycin, cycloserine, delamanid ethambutol, ethionamide, fluoroquinolone, fluoroquinolone antibiotic, isoniazid (INH), kanamycin, levofloxacin, linezolid, moxifloxacin, oxafloxacin, (6S)-2- nitro-6-{ [4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,l-^][l,3]oxazine (pretomanid; PA824), pyrazinamide, rifampin, rifampicin, rifabutin, streptomycin, and combinations thereof.
13. The method of claim 12, wherein the anti-tuberculosis drug is isoniazid (INH).
14. The method of claim 10, wherein the anti-tuberculosis drug is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg of the body weight of the patient.
15. The method of claim 14, wherein the anti-tuberculosis drug is administered at a concentration selected from the group consisting of lOmg/kg of the body weight of the patient.
16. The method of claim 10, wherein the combination therapy comprises chemotherapy.
17. The method of claim 10, wherein the compound is administered together, sequentially or separately from the combination therapy.
18. Use of a compound which enhances activity of an NAD+-dependent deacetylase in the manufacture of a medicament for preventing, treating or inhibiting intracellular mycobacterial infection in a patient in need thereof.
19. The use of claim 18, wherein the compound is a sirtuin enhancer.
20. The use of claim 18, wherein the NAD+-dependent deacetylase is selected from the group consisting of sirtuin 1, sirtuin 2, sirtuin 3, sirtuin 4, sirtuin 5, sirtuin 6, sirtuin 7, derivatives, homologues and combinations thereof.
21. The use of any of claims 18 to 20, wherein the NAD+-dependent deacetylase is sirtuin 1.
22. The use of any of claims 18 to 21, wherein the compound is selected from a group consisting of N- [2- [3 -(piperazin- 1 -ylmethyl)imidazo [2, 1 -b] [ 1 ,3 ] thiazol-6- yl]phenyl]quinoxaline-2-carboxamide (SRT1720), N-cyclopentyl-2-diazenyl-l-(3- methoxypropyl)pyrrolo[3,2-b]quinoxaline-3-carboxamide (SA3), diethyl l-benzyl-4- phenyl-l,4-dihydro-3,5-pyridinedicarboxylate (BML278), and salts and/or derivatives thereof.
23. The use of claim 22, wherein the compound is N- [2- [3 -(piperazin- 1- ylmethyl)imidazo [2, 1 -b] [ 1 ,3 ] thiazol-6-yl]phenyl] quinoxaline-2-carboxamide
(SRT1720) or a derivative thereof.
24. The use of any of claims 18 to 23, wherein the compound is administered at a concentration ranging from between 1 mg/kg to about 2000 mg/kg (2 g/kg) of the body weight of the patient.
25. The use of claim 24, wherein the compound is administered at a concentration of 10 mg/kg of the body weight of the patient.
26. The use of any of claims 18 to 25, wherein the intracellular mycobacterium is selected from the group consisting of a drug-resistant mycobacterium, a multidrug-resistant mycobacterium and an extensively drug-resistant mycobacterium.
27. The use of any of claims 18 to 26, wherein the mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium bovis BCG, Mycobacterium africanum, Mycobacterium canetti, Mycobacterium caprae, Mycobacterium microti, Mycobacterium leprae, Mycobacterium avium, Mycobacterium paratuberculosis and Mycobacterium pinnipedii.
28. The use of any of claims 18 to 27, wherein the compound is used in a combination therapy.
29. The use of claim 28, wherein the combination therapy comprises an anti-tuberculosis drug.
30. The use of claim 29, wherein the anti-tuberculosis drug is selected from the group consisting of amikacin, aminosalicylic acid, bedaquiline, capreomycin, cycloserine, delamanid ethambutol, ethionamide, fluoroquinolone antibiotic, isoniazid (INH), kanamycin, levofloxacin, linezolid, moxifloxacin, oxafloxacin, PA824, pyrazinamide, rifampin, rifampicin, rifabutin, streptomycin, and combinations thereof.
31. The use of claim 30, wherein the anti-tuberculosis drug is isoniazid (INH).
32. The use of claim 29, wherein the anti-tuberculosis drug is administered at a concentration ranging from between about 0.1 mg/kg to about 20 mg/kg of the body weight of the patient.
33. The use of claim 32, wherein the anti-tuberculosis drug is administered at a concentration of lOmg/kg of the body weight of the patient.
34. The use of claim 28, wherein the combination therapy comprises chemotherapy.
35. The method of claim 33, wherein the compound is administered together, sequentially or separately from the combination therapy.
36. The method of claims 1 to 17 or the use of claims 18 to 35, wherein the route of administration is selected from the group consisting of systemic administration, oral administration, intravenous administration and parenteral administration.
37. A pharmaceutical composition comprising a sirtuin enhancer in combination with an anti-tuberculosis drug or combination therapy.
38. The pharmaceutical composition of claim 37, wherein the sirtuin enhancer is administered prior to, together with, or sequentially after administration of the antituberculosis drug or combination therapy.
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Families Citing this family (4)

* Cited by examiner, † Cited by third party
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CN107582542B (en) * 2017-08-10 2020-04-24 北京悦康科创医药科技股份有限公司 PLGA nano-microspheres of Delamani and preparation method thereof
KR20220016157A (en) * 2019-05-30 2022-02-08 브리스톨-마이어스 스큅 컴퍼니 Cell localization signatures and combination therapies
DE112020004845T5 (en) * 2019-10-08 2022-08-04 Stellenbosch University IFIT POLYPEPTIDES AND USES IN TREATMENT OF TUBERCULOSIS INFECTIONS
CN112143798A (en) * 2020-09-30 2020-12-29 中国医学科学院病原生物学研究所 Application of NT5C3A as tuberculosis diagnosis molecular marker

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW200918542A (en) * 2007-06-20 2009-05-01 Sirtris Pharmaceuticals Inc Sirtuin modulating compounds
WO2009099643A1 (en) * 2008-02-07 2009-08-13 The J. David Gladstone Institutes Use of sirt1 activators or inhibitors to modulate an immune response
EP2993236A1 (en) * 2010-04-15 2016-03-09 Glaxosmithkline LLC Sirtuin activators and activation assays
BRPI1001052A2 (en) * 2010-04-22 2011-12-13 Ubea pharmaceutical formulation and process to reduce hepatotoxicity
SG11201501719UA (en) * 2012-09-07 2015-04-29 Agency Science Tech & Res Methods to inhibit intracellular growth of bacteria and to treat bacteria-mediated diseases
WO2015009883A1 (en) * 2013-07-18 2015-01-22 The Hamner Institutes Activators of nad-dependent protein deacteylases and uses thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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