US20120015904A1

US20120015904A1 - Biomarkers for diagnosis of transient ischemic attacks

Info

Publication number: US20120015904A1
Application number: US13/182,630
Authority: US
Inventors: Frank Sharp; Xinhua ZHAN; Glen C. JICKLING; S. Claiborne JOHNSTON
Original assignee: University of California
Current assignee: University of California
Priority date: 2010-07-14
Filing date: 2011-07-14
Publication date: 2012-01-19
Also published as: US20160237501A1; CN103097552A; EP2593566A4; EP2593566B1; CN103097552B; CA2804763C; US10047396B2; WO2012009547A3; WO2012009547A2; EP2593566A2; CA2804763A1

Abstract

The present invention provides methods and compositions for diagnosing and predicting the risk and cause of transient ischemic attacks (TIA).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 61/364,334, filed on Jul. 14, 2010, the entire disclosure of which is hereby incorporated herein by reference for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

This invention was made with Government support under Grant No. NSO56302, awarded by the National Institutes of Health. The government has certain rights in this invention.

FIELD OF THE INVENTION

BACKGROUND OF THE INVENTION

Transient ischemic attacks (TIAs) are common, affecting over 300,000 persons per year in the United States alone. Though TIA symptoms resolve by definition, TIAs are far from benign. As many as 25% of TIA patients have recurrent ischemic vascular events that occur within days to weeks following a TIA (1-3). Despite the high incidence and clinical importance, the development of therapies specifically targeted toward TIA has been limited by the paucity of knowledge regarding the underlying biology. Furthermore, the clinical diagnosis of TIA is imperfect and extensive evaluation in those incorrectly diagnosed with TIA is costly (4).
We have previously demonstrated that blood gene expression profiles in rats change following experimental ischemic strokes and TIAs (5). Very brief focal ischemia in rats, simulating human TIA, elicits a dramatic change in brain tissue characterized by increased Heat Shock Protein (HSP70) expression, microglial activation and macrophage infiltration (6). This change in brain cellular function and inflammation alters blood immune cells, a process that can be detected using whole genome expression analysis (5). Furthermore, the genes and associated functional pathways differ markedly between very brief focal ischemia and ischemic stroke (5).
Human TIAs have also been associated with alterations in systemic inflammation. TIA patients tend to have elevated C-reactive protein (CRP) (7), IL-6, VCAM-1 and cytokine levels, as well as elevated leukocyte counts (8-10). Lp-PLA2, a marker of unstable atherosclerotic plaque, is also associated with TIA (11-12) as are fibrinogen (13-14) and D-Dimer (15). Whether such biological differences represent a cause or consequence of TIA remains unclear. However, better understanding of the pathophysiology represented by such differences will facilitate development of treatments targeted to TIA.
Gene expression has been useful for identifying differences between patients with ischemic stroke and controls (16-18), but such studies have not been applied to TIA. The present invention is based, in part, on gene expression profiles that provide insight into the immunological differences that exist in patients with TIAs.

BRIEF SUMMARY OF THE INVENTION

The present invention provides compositions and methods for determining the occurrence, predicting the risk of occurrence and predicting the cause of transient ischemic attacks.
Accordingly, in one aspect, the invention provides methods for diagnosing a transient ischemic attack (TIA) or a predisposition for experiencing TIA, the method comprising: determining a level of expression of a plurality of TIA-associated biomarkers in a biological sample from a patient, wherein an increase or decrease of the level of expression compared to a control indicates that the patient has suffered or is at risk of experiencing TIA, wherein the plurality of TIA-associated biomarkers is selected from the biomarkers set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and 9.
In some embodiments, the methods further comprise obtaining a biological sample from the patient. In some embodiments, the biological sample is blood, serum or plasma.
In some embodiments, the determining step is performed at 3 or fewer hours after a suspected ischemic event. In some embodiments, thee determining step is performed at 3 or more hours after a suspected ischemic event, for example, at about 6, 12, 24, 36, 48 or more hours after a suspected ischemic event. In some embodiments, the determining step is performed at least 24 hours after a suspected ischemic event.
In some embodiments, an increased expression level of one or more or all TIA-associated biomarkers selected from the group consisting of DKFZP434B061, FAM55D, FLJ30375, IGFBP5, LTBR and SCN2A indicates that the patient has suffered or is at risk of experiencing TIA. In some embodiments, an increased expression level of one or more or all TIA-associated biomarkers selected from the group consisting of GABRB2, ELAVL3, TWIST1, DPPA4, DKFZP434P211, DLX6, ZNF479, ASTN2, SNX31, ALS2CR11, LOC440345 indicates that the patient has suffered or is at risk of experiencing TIA.
In some embodiments, an increased expression level of one or more or all TIA-associated biomarkers selected from the group consisting of GABRB2, ELAVL3, COL1A1, SHOX2, GABRB2, TWIST1, DPPA4, DKFZP434P211, WIT1, SOX9, DLX6, ANXA3, EPHA3, SOX11, SLC26A8, CCRL1, FREM2, STOX2, ZNF479, LOC338862, ASTN2, FOLH1, SNX31, KREMEN1, ZNF479, ALS2CR11, FIGN, RORB, LOC732096, GYPA, ALPL, LHX2, GALNT5, SRD5A2L2, GALNT14, OVOL2, BMPR1B, UNC5B, ODZ2, ALPL, RASAL2, SHOX, C19orf59, ZNF114, SRGAP1, ELAVL2, NCRNA00032, LOC440345, FLJ30375, TFPI, PTGR1, ROBO1, NR2F2, GRM5, LUM, FLJ39051, COL1A2, CASP5, OPCML, TTC6, TFAP2B, CRISP2, SOX11, ANKRD30B, FLJ39051, SCN2A, MYNN, FOXA2, DKFZP434B061, LOC645323, SNIP, LOC645323, LOC374491, ADAM30, SIX3, F1136144, CARDS, KREMEN1, RP1-127L4.6, FAM149A, B3GAT2, SPOCK3, G30, ITGBL1, IQGAP3, C7orf45, ZNF608, LOC375010, LRP2, TGFB2, SHOX2, HOXC4///HOXC6, ELTD1, FAM182B///RP13-401N8.2, PRO0478, LIFR, FOLH1, EHF, NDST3, BRUNOL5, LOC728460, PDE1A, POU2AF1, FAT1, PCDH11X///PCDH11Y, F1137786, SLC22A4, DHRS13, EHF, MEG3, PIWIL1, LOC203274, LOC100133920///LOC286297, DMRT1, ADM, VWA3B, GAFA3, HESX1, ADAMDEC1, CAV1, LAMB4, TPTE, PPP1R1C, HPSE, AIM2, RUNDC3B, CARD16, FAM124A, MGC39584, OSM, RFX2, MYBPC1, LTBR, C18orf2, SNRPN, FLJ36031, IL1B, TRPM1, OSTCL, MAPK14, KCNJ15///LOC100131955, FIGN, HNT, S100A12, CHIT1, C7orf53, FAM13A1, GNAO1, MAPK14, FAM55D, PRKD2, LIMK2, C18orf54, IGFBP5, EVI1, PLSCR1, FOXC1, LOC646627, ZNF462, CNTLN, ZNF438, DEFB105A///DEFB105B, LOC340017, C1orf67, ACSL1, ADH1B, SLC2A14///SLC2A3, IL1B, ST3GAL4, UBE2J1, PNPLA3 and PAPPA indicates that the patient has suffered or is at risk of experiencing TIA.
In some embodiments, a decreased expression level of one or more or all TIA-associated biomarkers selected from the group consisting of ATG9B, DIP2C, EDAR, GSTM1, GUSBL2, SMURF2, ZNF512B indicates that the patient has suffered or is at risk of experiencing TIA.
In some embodiments, a decreased expression level of one or more or all TIA-associated biomarkers selected from the group consisting of NBPF10///RP11-9412.2, SFXN1, SPIN3, UNC84A, OLFM2, PPM1K, P2RY10, ZNF512B, MORF4L2, GIGYF2, ERAP2, SLFN13, LOC401431, MED6, BAIAP2L1///LOC100128461, LNPEP, MBNL1, NOS3, MCF2L, KIAA1659, SCAMPS, LOC648921, ANAPC5, SPON1, FUS, GPR22, GAL3ST4, METTL3, LOC100131096, FAAH2, SMURF2, SNRPN, FBLN7, GLS, G3BP1, RCAN3, EPHX2, DIP2C, CCDC141, CLTC, FOSB, CACNA1I, UNQ6228, ATG9B, AK5, SPIN3, RBM14, SNRPN, MAN1C1, HELLS, EDAR, SLC3A1, ZNF519, LOC100130070///LOC100130775///LOC100131787///LOC100131905///LOC100132291///LOC100132488///RPS27, ZC3H12B, IQGAP2, SOX8, WHDC1L2, TNPO1, TNFRSF21, TSHZ2, DMRTC1///DMRTC1B, GSTM1, GSTM2, PNMA6A, CAND1, CCND3, GSTM1, GUSBL2 indicates that the patient has suffered or is at risk of experiencing TIA.
In some embodiments, an increased expression level of 2, 3, 4, 5, 6, 7, or more or all, TIA-associated biomarkers selected from the group consisting of F1130375, SCN2A, DKFZP434B061, LTBR, FAMSSD, and IGFBPS and a decreased expression level of 2, 3, 4, 5, 6, 7, or more or all, TIA-associated biomarkers selected from the group consisting of GUSBL2, GSTM1, EDAR, ATG9B, DIP2C, SMURF2, and ZNF512B indicates that the patient has suffered or is at risk of experiencing TIA.
In some embodiments, the methods further comprise determining the level of expression of one or biomarkers selected from the group consisting of CNTN4, TLR5, GPR84, BCL6, NELL2, APBA2 and MLL. In some embodiments, detection of an increased level of expression of a biomarker selected from CNTN4, TLR5, GPR84 and BCL6 indicates that the patient has suffered or is at risk of experiencing TIA. In some embodiments, detection of a decreased level of expression of a biomarker selected from NELL2, APBA2 and MLL indicates that the patient suffered or is at risk of experiencing TIA.
In some embodiments, the methods further comprises the step of determining the cause of stroke. In some embodiments, the patient overexpresses a plurality of genes listed in Table 7, indicative of a chronic inflammatory state. In some embodiments, the level of expression of one or more or all genes selected from the group consisting of MMP16, MMP19, MMP26, COL1A1, COL1A2, COL3A1, COL10A1, COL11A1, COL25A1, COL27A1, FGFs and EGFR is increased in comparison to the control, and the patient is determined to have atherosclerosis.
In some embodiments, the patient is exhibiting symptoms of TIA. In some embodiments, the patient is asymptomatic.
In some embodiments, the methods further comprise the step of providing an appropriate treatment or prevention regime for TIA to the patient.
In some embodiments, the level of expression of the biomarker is determined at the transcriptional level. For example, RNA levels of the biomarker can be determined. The RNA can be mRNA, rRNA, tRNA or microRNA (miRNA). In some embodiments, the level of RNA expression is determined using a microarray.
In some embodiments, the level of expression is determined by detecting hybridization of an TIA-associated gene probe to gene transcripts of the biomarkers in the biological sample.
In some embodiments, the hybridization step is performed on a nucleic acid microarray chip. In some embodiments, the hybridization step is performed in a microfluidics assay plate.
In some embodiments, the level of expression is determined by amplification of gene transcripts of the biomarkers. In some embodiments, the amplification reaction is a polymerase chain reaction (PCR).
In some embodiments, the level of expression of the biomarker is determined at the protein level.
In some embodiments, the level of expression of at least 15 biomarkers is determined. In some embodiments, the level of expression of about 15-85, 20-70, 30-60 or 40-50 biomarkers are determined. In some embodiments, about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more, biomarkers are determined. The levels of expression of the plurality of biomarkers can be concurrently or sequentially determined.
In some embodiments, the control is the expression level of a plurality of expressed endogenous reference biomarkers. In some embodiments, the one or more or all endogenous reference biomarkers are listed in Table 3. In some embodiments, the TIA-associated biomarkers are overexpressed or underexpressed at least about 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2.0-fold, 2.1 fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3.0-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold or 3.5-fold, or more, in comparison to the expression levels of a plurality of stably expressed endogenous reference biomarkers, e.g., those listed in Table 3. In some embodiments, the expression levels of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, or all, the endogenous reference biomarkers selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4 KB, CRTC1, HADHA, MAP1LC3B, KAT5, CDC2L1///CDC2L2, GTSE1, CDC2L1///CDC2L2, TCF25, CHP, LRRC40, hCG_—2003956/1/LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHC5, C9orf23, LRRC45, NACC1, LOC100133445///LOC115110, PEX16 are determined as a control.
In some embodiments, the control is the expression level of the same biomarker in a healthy individual. In some embodiments, the control is the expression level of the same biomarker in an individual who has not experienced a vascular event (e.g., TIA, ischemic stroke, myocardial infarction, peripheral vascular disease, or venous thromboembolism). In some embodiments, the control is a threshold level of expression, e.g., of the same TIA-associated biomarker, optionally normalized to the expression level of a stably expressed endogenous reference biomarker, representative of a population of healthy individuals.
In a related aspect, the invention provides a solid support comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9, wherein the nucleic acids are attached to the solid support. In some embodiments, the solid support comprises a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Tables 1 and 2. The solid support can further comprise a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 3. The solid support can be attached to at least about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 75, 80, 85, 90, 95 or 100, or more, genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8, 9 and/or 3. The solid support can be a microarray.
In one embodiment, the solid support comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more or all, nucleic acids that hybridize to a plurality of the genes selected from the group consisting of GUSBL2, GSTM1, F1130375, SCN2A, DKFZP434B061, EDAR, ATG9B, DIP2C, LTBR, SMURF2, FAM55D, IGFBP5, and ZNF512B.

DEFINITIONS

Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry and nucleic acid chemistry and hybridization described below are those well known and commonly employed in the art. Standard techniques are used for nucleic acid and peptide synthesis. Generally, enzymatic reactions and purification steps are performed according to the manufacturer's specifications. The techniques and procedures are generally performed according to conventional methods in the art and various general references (see generally, Sambrook et al. MOLECULAR CLONING: A LABORATORY MANUAL, 3rd ed. (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. and Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, 1990-2008, Wiley Interscience), which are provided throughout this document. The nomenclature used herein and the laboratory procedures in analytical chemistry, and organic synthetic described below are those well known and commonly employed in the art. Standard techniques, or modifications thereof, are used for chemical syntheses and chemical analyses.
“Ischemia” or “ischemic event” as used herein refers to diseases and disorders characterized by inadequate blood supply (i.e., circulation) to a local area due to blockage of the blood vessels to the area. Ischemia includes for example, strokes and transient ischemic attacks. Strokes include, e.g., ischemic stroke (including, but not limited to, cardioembolic strokes, atheroembolic or atherothrombotic strokes, i.e., strokes caused by atherosclerosis in the carotid, aorta, heart, and brain, small vessel strokes (i.e., lacunar strokes), strokes caused by diseases of the vessel wall, i.e., vasculitis, strokes caused by infection, strokes caused by hematological disorders, strokes caused by migraines, and strokes caused by medications such as hormone therapy), hemorrhagic ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.
The term “transient ischemic attack,” “TIA,” or “mini-stroke” interchangeably refer to a change in the blood supply to a particular area of the brain, resulting in brief neurologic dysfunction that persists, by definition, for less than 24 hours. By definition, a TIA resolves within 24 hours, but most TIA symptoms resolve within a few minutes. If symptoms persist longer, then it is categorized as a stroke. Symptoms include temporary loss of vision (typically amaurosis fugax); difficulty speaking (aphasia); weakness on one side of the body (hemiparesis); numbness or tingling (paresthesia), usually on one side of the body, and dizziness, lack of coordination or poor balance. The symptoms of a TIA usually last a few seconds to a few minutes and most symptoms disappear within 60 minutes.
“TIA reference expression profile” refers to the pattern of expression of a set of genes (e.g., a plurality of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9 differentially expressed (i.e., overexpressed or underexpressed) in an individual who has suffered or is at risk of experiencing TIA relative to the expression in a control (e.g., the expression level in an individual free of an ischemic event or the expression level of a stably expressed endogenous reference biomarker). A gene from Tables 1, 5B, 5C, 5D, 7, 8 and/or 9 that is expressed at a level that is at least about 1.5-, 1.6-, 1.7-, 1.8-, 1.9-, 2.0-, 2.1-, 2.2-, 2.3-, 2.4-, 2.5-, 2.6-, 2.7-, 2.8-, 2.9-, 3.0-, 3.1-, 3.2-, 3.3-, 3.4- or 3.5-fold higher than the level in a control is a gene overexpressed in TIA and a gene from Tables 2, 5A, 5C, 5D, 7, 8 and/or 9 that is expressed at a level that is at least about 1.5-, 1.6-, 1.7-, 1.8-, 1.9-, 2.0-, 2.1-, 2.2-, 2.3-, 2.4-, 2.5-, 2.6-, 2.7-, 2.8-, 2.9-, 3.0-, 3.1-, 3.2-, 3.3-, 3.4- or 3.5-fold lower than the level in a control is a gene underexpressed in TIA. Alternately, genes that are expressed at a level that is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% higher than the level in a control is a gene overexpressed in TIA and a gene that is expressed at a level that is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% lower than the level in a control is a gene underexpressed in TIA.
A “plurality” refers to two or more, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or more (e.g., genes). In some embodiments, a plurality refers to concurrent determination of expression levels about 15-85, 20-60 or 40-50 genes, for example, about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more, genes. In some embodiments, “plurality” refers to all genes listed in one or more or all tables, e.g., all genes listed in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9.
The terms “patient,” “subject” or “individual” interchangeably refers to a mammal, for example, a human or a non-human mammal, including primates (e.g., macaque, pan troglodyte, pongo), a domesticated mammal (e.g., felines, canines), an agricultural mammal (e.g., bovine, ovine, porcine, equine) and a laboratory mammal or rodent (e.g., rattus, murine, lagomorpha, hamster, guinea pig).
“Sample” or “biological sample” includes sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histologic purposes. Such samples include blood, sputum, tissue, lysed cells, brain biopsy, cultured cells, e.g., primary cultures, explants, and transformed cells, stool, urine, etc. A biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate, e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish.
“Array” as used herein refers to a solid support comprising attached nucleic acid or peptide probes. Arrays typically comprise a plurality of different nucleic acid or peptide probes that are coupled to a surface of a substrate in different, known locations. These arrays, also described as “microarrays” or colloquially “chips” have been generally described in the art, for example, U.S. Pat. Nos. 5,143,854, 5,445,934, 5,744,305, 5,677,195, 6,040,193, 5,424,186 and Fodor et al., Science, 251:767-777 (1991). These arrays may generally be produced using mechanical synthesis methods or light directed synthesis methods which incorporate a combination of photolithographic methods and solid phase synthesis methods. Techniques for the synthesis of these arrays using mechanical synthesis methods are described in, e.g., U.S. Pat. No. 5,384,261. Arrays may comprise a planar surface or may be nucleic acids or peptides on beads, gels, polymeric surfaces, fibers such as fiber optics, glass or any other appropriate substrate as described in, e.g., U.S. Pat. Nos. 5,770,358, 5,789,162, 5,708,153, 6,040,193 and 5,800,992. Arrays may be packaged in such a manner as to allow for diagnostics or other manipulation of an all inclusive device, as described in, e.g., U.S. Pat. Nos. 5,856,174 and 5,922,591.
The term “gene” means the segment of DNA involved in producing a polypeptide chain; it includes regions preceding and following the coding region (leader and trailer) as well as intervening sequences (introns) between individual coding segments (exons).
The terms “nucleic acid” and “polynucleotide” are used interchangeably herein to refer to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form. The term encompasses nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs).
Unless otherwise indicated, a particular nucleic acid sequence also encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide.
The phrase “stringent hybridization conditions” refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acid, but to no other sequences. Stringent hybridization conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology—Hybridization with Nucleic Probes, “Overview of principles of hybridization and the strategy of nucleic acid assays” (1993). Generally, stringent hybridization conditions are selected to be about 5-10° C. lower than the thermal melting point for the specific sequence at a defined ionic strength Ph. The T_mis the temperature (under defined ionic strength, Ph, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at T_m, 50% of the probes are occupied at equilibrium). Stringent hybridization conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at Ph 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotides) and at least about 60° C. for long probes (e.g., greater than 50 nucleotides). Stringent hybridization conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, optionally 10 times background hybridization. Exemplary stringent hybridization conditions can be as following: 50% formamide, 5×SSC, and 1% SDS, incubating at 42° C., or, 5×SSC, 1% SDS, incubating at 65° C., with wash in 0.2×SSC, and 0.1% SDS at 65° C.
Nucleic acids that do not hybridize to each other under stringent hybridization conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions. Exemplary “moderately stringent hybridization conditions” include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37° C., and a wash in 1×SSC at 45° C. A positive hybridization is at least twice background. Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency.
The terms “isolated,” “purified,” or “biologically pure” refer to material that is substantially or essentially free from components that normally accompany it as found in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein that is the predominant species present in a preparation is substantially purified. The term “purified” denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. Particularly, it means that the nucleic acid or protein is at least 85% pure, more preferably at least 95% pure, and most preferably at least 99% pure.
The term “heterologous” when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
An “expression vector” is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell. The expression vector can be part of a plasmid, virus, or nucleic acid fragment. Typically, the expression vector includes a nucleic acid to be transcribed operably linked to a promoter.
The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer.
The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, α-carboxyglutamate, and O-phosphoserine. “Amino acid analogs” refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. “Amino acid mimetics” refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.
Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
“Conservatively modified variants” applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are “silent variations,” which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence.
As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
The following eight groups each contain amino acids that are conservative substitutions for one another:

- 1) Alanine (A), Glycine (G);
- 2) Aspartic acid (D), Glutamic acid (E);
- 3) Asparagine (N), Glutamine (Q);
- 4) Arginine I, Lysine (K);
- 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V);
- 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W);
- 7) Serine (S), Threonine (T); and
- 8) Cysteine (C), Methionine (M)
- (see, e.g., Creighton, Proteins (1984)).
- The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, or 95% identity over a specified region of a TIA-associated gene (e.g., a gene set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Such sequences are then said to be “substantially identical.” This definition also refers to the compliment of a test sequence. Preferably, the identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.

For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. For sequence comparison of nucleic acids and proteins to TIA-associated nucleic acids and proteins, the BLAST and BLAST 2.0 algorithms and the default parameters discussed below are used.
A “comparison window”, as used herein, includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, e.g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).
A preferred example of algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410 (1990), respectively. BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) of 10, M=5, N=−4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=−4, and a comparison of both strands.
The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.
An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below. Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequence.
The phrase “selectively (or specifically) hybridizes to” refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence under stringent hybridization conditions when that sequence is present in a complex mixture (e.g., total cellular or library DNA or RNA).
By “host cell” is meant a cell that contains an expression vector and supports the replication or expression of the expression vector. Host cells may be, for example, prokaryotic cells such as E. coli or eukaryotic cells such as yeast cells or mammalian cells such as CHO cells.
“Inhibitors,” “activators,” and “modulators” of expression or of activity are used to refer to inhibitory, activating, or modulating molecules, respectively, identified using in vitro and in vivo assays for expression or activity, e.g., ligands, agonists, antagonists, and their homologs and mimetics. The term “modulator” includes inhibitors and activators Inhibitors are agents that, e.g., inhibit expression of a polypeptide or polynucleotide of the invention or bind to, partially or totally block stimulation or enzymatic activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity of a polypeptide or polynucleotide of the invention, e.g., antagonists. Activators are agents that, e.g., induce or activate the expression of a polypeptide or polynucleotide of the invention or bind to, stimulate, increase, open, activate, facilitate, enhance activation or enzymatic activity, sensitize or up regulate the activity of a polypeptide or polynucleotide of the invention, e.g., agonists. Modulators include naturally occurring and synthetic ligands, antagonists, agonists, small chemical molecules and the like. Assays to identify inhibitors and activators include, e.g., applying putative modulator compounds to cells, in the presence or absence of a polypeptide or polynucleotide of the invention and then determining the functional effects on a polypeptide or polynucleotide of the invention activity. Samples or assays comprising a polypeptide or polynucleotide of the invention that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of effect. Control samples (untreated with modulators) are assigned a relative activity value of 100% Inhibition is achieved when the activity value of a polypeptide or polynucleotide of the invention relative to the control is about 80%, optionally 50% or 25-1%. Activation is achieved when the activity value of a polypeptide or polynucleotide of the invention relative to the control is 110%, optionally 150%, optionally 200-500%, or 1000-3000% higher.
The term “test compound” or “drug candidate” or “modulator” or grammatical equivalents as used herein describes any molecule, either naturally occurring or synthetic, e.g., protein, oligopeptide (e.g., from about 5 to about 25 amino acids in length, preferably from about 10 to 20 or 12 to 18 amino acids in length, preferably 12, 15, or 18 amino acids in length), small organic molecule, polysaccharide, lipid, fatty acid, polynucleotide, RNAi, oligonucleotide, etc. The test compound can be in the form of a library of test compounds, such as a combinatorial or randomized library that provides a sufficient range of diversity. Test compounds are optionally linked to a fusion partner, e.g., targeting compounds, rescue compounds, dimerization compounds, stabilizing compounds, addressable compounds, and other functional moieties. Conventionally, new chemical entities with useful properties are generated by identifying a test compound (called a “lead compound”) with some desirable property or activity, e g, inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis.
A “small organic molecule” refers to an organic molecule, either naturally occurring or synthetic, that has a molecular weight of more than about 50 Daltons and less than about 2500 Daltons, preferably less than about 2000 Daltons, preferably between about 100 to about 1000 Daltons, more preferably between about 200 to about 500 Daltons.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B. Heat map of 460 genes/probes differentially expressed in blood between Transient Ischemic Attack (TIA) patients and controls (FDR≦0.05, absolute fold change >1.5). Each column on the X axis represents 1 patient, with 24 TIA patients (blue) and 27 controls (pink). Each row on the Y axis represents individual genes. TIAs cluster separately from controls as indicated by the green arrow (top). Within TIA subjects, at least two clusters are apparent as indicated by the red arrow. These two TIA clusters are labeled TIA1 and TIA2. Two TIA patients (ID: 57 and 90) clustered with controls. Three controls (ID: 42, 68, and 74) clustered with TIAs. Red=up regulation. Green=down regulation. ID=subjects ID. Diagnosis=blue (TIA) and pink (Controls).

FIG. 2. Cross-validation results for the 34 out of 460 TIA regulated genes that distinguish TIA patients from control subjects. The probability of predicted diagnosis is shown on the Y axis, and subjects are shown on the X axis. TIA patients are shown on the right, and Control subjects on the left. The predicted probability of TIA is shown in red, and the predicted probability of being control is shown in blue. TIA patients were distinguished from controls with 87.5% sensitivity and 96.3% specificity using a 10-fold cross-validation.

FIG. 3. Cross-validation results for the 26 up-regulated genes identified by PAM to distinguish the TIA1 from TIA2 groups. The probability of the predicted diagnosis is shown on the Y axis, and subjects are shown on the X axis. TIA1 subjects are shown on the left, and TIA2 subjects on the right. The predicted probability of TIA2 is shown in red, and the predicted probability of TIA1 is shown in blue. TIA1 could be distinguished from TIA2 patients with 100% sensitivity and 100% specificity.

FIGS. 4A-B. MMP16 (A) and MMP26 (B) transcript expression in TIA patients (blue) and control subjects (pink). A. MMP16. There was no difference in MMP16 expression for all control subjects compared to all TIA patients (A1). There was a significant increase in expression of MMP16 in the TIA1 patients compared to both control (p=1.35×10⁻⁷) and TIA2 groups (p=2.19×10⁻⁷) and no difference in MMP16 expression between control subjects and TIA2 patients (A2). B. MMP26. There was no difference in MMP26 expression for all control subjects compared to all TIA patients (B1). There was a significant increase in expression of MMP26 in the TIA1 group compared to both control (p=6.67×10⁻⁴) and TIA2 groups (p=8.55×10⁻⁴) and no difference in MMP26 expression between control subjects and TIA2 patients (B2). The X axis shows categories of subjects. The Y axis shows the log 2-intensity/RNA expression. Pink=controls. Dark blue=All TIA or TIA1. Light blue=TIA2.

DETAILED DESCRIPTION

1. Introduction

Although transient ischemic attacks (TIAs) are common, the underlying biology remains poorly understood. The present invention is based, in part, on the discovery that TIAs differentially regulate gene expression in blood. The differentially regulated genes indicative of the occurrence or risk of occurrence of TIAs find use in the diagnosis, treatment and prevention of TIAs in patients. Patients with recent TIAs can be differentiated from controls without previous vascular events using gene expression profiles in blood. In addition, human patients appear to develop different immune response subtypes following transient ischemic attacks.

2. Individuals Who Can Benefit from the Present Methods

Individuals who will benefit from the present methods may be exhibiting symptoms of TIA or stroke. Alternatively, the subject may be suspected of having experienced TIA. In some embodiments, the subject has not experienced and/or is not at risk of having an intracerebral hemorrhage. In some embodiments, the subject has not experienced and/or is not at risk of having an intracerebral hemorrhage or hemorrhagic stroke. In some embodiments, the subject has been diagnosed as having not experienced and/or not at risk of having an intracerebral hemorrhage or hemorrhagic stroke.
In some embodiments, the levels of expression of the panel of biomarkers is determined within 3 hours of a suspected ischemic event. In some embodiments, the levels of expression of the panel of biomarkers are determined at 3 or more hours after a suspected ischemic event. In some embodiments, the levels of expression of the panel of biomarkers are determined within 6, 12, 18, 24, 36, 48 hours of a suspected ischemic event.
In some cases, the subject is asymptomatic, but may have a risk or predisposition to experiencing TIA, e.g., based on genetics, a related disease condition, environment or lifestyle. For example, in some embodiments, the patient suffers from a chronic inflammatory condition, e.g., has an autoimmune disease (e.g., rheumatoid arthritis, Crohn's disease inflammatory bowel disease), atherosclerosis, hypertension, or diabetes. In some embodiments, the patient has high LDL-cholesterol levels or suffers from a cardiovascular disease (e.g., atherosclerosis, coronary artery disease). In some embodiments, the patient has an endocrine system disorder, a neurodegenerative disorder, a connective tissue disorder, or a skeletal and muscular disorder. Exemplary disorders associated with, related to, or causative of TIA are provided in Table 7.
In some embodiments, the patient may have a neurological disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADH1B, AK5, ANXA3, APBA2, ASTN2 (includes EG:23245), BCL6, BMPR1B, CASP5, CAV1, CNTN4, DIP2C, ELAVL2, EPHX2, ERAP2, FAM124A, FAM13A, FAM149A, FAT1, FOLH1, FOXC1, GABRB2, GIGYF2, GNAO1, GRM5, GSTM1, HESX1, HOXC6, IGFBP5, IL1B, IQGAP2, ITGBL1, LAMB4, LIFR, LTBR, MECOM, NBPF10, NDST3, NELL2, NOS3, NTM, ODZ2, OLFM2, OPCML, PDE1A, RFX2, ROBO1, S100A12, SCN2A, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SOX9, SPOCK3, SPON1, TGFB2, TLR5, TNFRSF21, TRPM1, TSHZ2, TTC6 (includes EG:115669), UNC5B, UNC84A and ZNF608.
In some embodiments, the patient may have a skeletal or muscular disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ASTN2 (includes EG:23245), BCL6, BMPR1B, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A1, COL1A2, DIP2C, DNAH14, EDAR, ELAVL2, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, GIGYF2, GNAO1, HOXC6, IL1B, KCNJ15, LAMB4, LIFR, LTBR, LUM, MAPK14, MYBPC1, NOS3, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SCN2A, SHOX, SLC22A4 (includes EG:6583), SOX9, SPOCK3, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), TWIST1, UNC5B, VWA3B and ZNF438.
In some embodiments, the patient may have an inflammatory disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ANXA3, APBA2, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CAV1, CCND3, CCRL1, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, ERAP2, FAM124A, FBLN7, FOSB, FREM2, GABRB2, GRM5, IL1B, KCNJ15, LAMB4, LHX2, LNPEP, LRP2, LTBR, LUM, MAPK14, MECOM, MYBPC1, NOS3, ODZ2, OPCML, OSM, PAPPA, PDE1A, PPP1R1C, ROBO1, RUNDC3B, S100A12, SCN2A, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SMURF2, SNRPN, SPON1, TGFB2, TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), TWIST1, UNC5B, VWA3B and ZNF438.
In some embodiments, the patient may have a cardiovascular disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ALPL, ASTN2 (includes EG:23245), BCL6, BMPR1B, C18ORF54, CACNA1I, CARD16, CAV1, CNTN4, DMRT1, DNAH14, EDAR, EPHX2, ERAP2, FAM13A, FOLH1, FOSB, FREM2, GABRB2, GRM5, GSTM1, IL1B, IQGAP2, LIFR, LTBR, MAN1C1, MAPK14, MBNL1, MCF2L, MECOM, MYBPC1, NOS3, NTM, ODZ2, OLFM2, OPCML, PAPPA, PDE1A, ROBO1, RORB, S100A12, SMURF2, SNRPN, SOX9, SPOCK3, SPON1, TFP1, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have an immunological disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ANXA3, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CCRL1, CLTC, CNTN4, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FAT1, FOSB, GABRB2, GOLGA6L2, GSTM1, GUSBL2, IL1B, IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14, MYBPC1, NELL2, NOS3, NTM, ODZ2, OPCML, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), SNRPN, SPON1, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have a metabolic disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, EPHX2, FAT1, FOXA2, GABRB2, GUSBL2, IGFBP5, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have an endocrine system disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2, GUSBL2, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SHOX, SLC22A4 (includes EG:6583), SLC2A3, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have an autoimmune disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, GUSBL2, IL1B, IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14, MYBPC1, NELL2, ODZ2, OPCML, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), SNRPN, SPON1, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have diabetes and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2, GUSBL2, IL1B, IQGAP2, ITGBL1, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have a connective tissue disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A1, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SHOX, SLC22A4 (includes EG:6583), TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have rheumatic disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have arthritis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBOT, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B, ZNF438.
In some embodiments, the patient may have atherosclerosis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, ASTN2 (includes EG:23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2, FOSB, FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM, ODZ2, OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have inflammatory bowel disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, APBA2, ASTN2 (includes EG:23245), CARD8, DIP2C, DNAH14, ERAP2, FBLN7, FREM2, GRM5, IL1B, LHX2, LNPEP, LTBR, MECOM, NOS3, ODZ2, OPCML, PAPPA, PDE1A, PPP1R1C, ROBO1, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SNRPN, SPON1, TGFB2, TLR5, VWA3B and ZNF438.
In some embodiments, the patient may have non-insulin-dependent diabetes mellitus and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), CARD8, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, EPHA3, FAT1, FOXA2, GABRB2, IL1B, IQGAP2, ITGBL1, MBNL1, NOS3, NTM, ODZ2, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SPON1, SRGAP1, TLR5, UNC84A and VWA3B.
In some embodiments, the patient may have rheumatoid arthritis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have coronary artery disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, ASTN2 (includes EG:23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2, FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM, ODZ2, OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have Crohn's disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, APBA2, ASTN2 (includes EG:23245), CARD8, DIP2C, DNAH14, ERAP2, FBLN7, FREM2, GRM5, LHX2, LNPEP, MECOM, ODZ2, OPCML, PAPPA, PDE1A, PPP1R1C, ROBO1, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SNRPN, SPON1, TGFB2, TLR5, VWA3B and ZNF438.
In some embodiments, the patient may have a neurodegenerative disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ASTN2 (includes EG:23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM, NDST3, NOS3, OPCML, RFX2, SCN2A, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SPON1, TSHZ2 and ZNF608.
In some embodiments, the patient may have Alzheimer's disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ASTN2 (includes EG:23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM, NDST3, NOS3, OPCML, RFX2, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SPON1, TSHZ2 and ZNF608.

3. Biomarkers Indicative of the Occurrence or Risk of TIA

Overexpressed biomarkers indicative of the occurrence of TIA or useful to predict the risk of experiencing TIA are listed in Table 1. In practicing the present methods, the expression levels of a plurality of biomarkers from Table 1 are determined, optionally in combination with other TIA-associated biomarkers described herein (e.g., in Tables 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9) and known in the art.
Preferably, the expression levels of a plurality in the range of about 15-85 total biomarkers are determined, for example, about 20-70, 30-60 or 40-50 biomarkers. The expression levels of the biomarkers can be concurrently or sequentially determined. In some embodiments, the expression levels of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 45, 50, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more, biomarkers listed in Table 1 are determined, optionally in combination with other TIA-associated biomarkers described herein (e.g., in Tables 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9) and known in the art.
In patients who have experienced TIA or who are at risk of developing TIA, the biomarkers of Table 1 are overexpressed in comparison to a control level of expression. A control level of expression can refer to the level of expression of the same biomarker in an individual who has not had and is not at risk for a vascular event or the level of expression of a stably expressed endogenous control gene. In patients who have experienced TIA or who are at risk of developing TIA, the biomarkers of Table 1 are overexpressed at least 1.5-fold, e.g., at least 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2.0-fold, 2.1-fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3.0-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold or 3.5-fold, or more, in comparison to a control level of expression.

TABLE 1

TIA-associated biomarkers that are upregulated

				Fold-	Fold-
				Change	Change (TIA vs.
			RefSeq	(TIA vs.	Control)
Probeset ID	Gene Symbol	Gene Title	Transcript ID	Control)	(Description)

1557122_s_at	GABRB2	gamma-aminobutyric acid	NM_000813 ///	3.49668	TIA up vs Control
		(GABA) A receptor, beta 2	NM_021911
227612_at	ELAVL3	ELAV (embryonic lethal,	NM_001420 ///	3.23425	TIA up vs Control
		abnormal vision,	NM_032281
		Drosophila)-like 3 (Hu
		antigen C)
1556499_s_at	COL1A1	collagen, type I, alpha 1	NM_000088	2.87107	TIA up vs Control
210135_s_at	SHOX2	short stature homeobox 2	NM_003030 ///	2.86893	TIA up vs Control
			NM_006884
242344_at	GABRB2	gamma-aminobutyric acid	NM_000813 ///	2.72458	TIA up vs Control
		(GABA) A receptor, beta 2	NM_021911
213943_at	TWIST1	twist homolog 1	NM_000474	2.72279	TIA up vs Control
		(Drosophila)
241199_x_at	DPPA4	developmental	NM_018189	2.68174	TIA up vs Control
		pluripotency associated 4
222253_s_at	DKFZP434P211	POM121 membrane	NR_003714	2.61011	TIA up vs Control
		glycoprotein-like 1
		pseudogene
206954_at	WIT1	Wilms tumor upstream	NM_015855 ///	2.58643	TIA up vs Control
		neighbor 1	NR_023920
202935_s_at	SOX9	SRY (sex determining	NM_000346	2.45928	TIA up vs Control
		region Y)-box 9
239309_at	DLX6	distal-less homeobox 6	NM_005222	2.4523	TIA up vs Control
209369_at	ANXA3	annexin A3	NM_005139	2.41095	TIA up vs Control
211164_at	EPHA3	EPH receptor A3	NM_005233 ///	2.39314	TIA up vs Control
			NM_182644
204913_s_at	SOX11	SRY (sex determining	NM_003108	2.34727	TIA up vs Control
		region Y)-box 11
237340_at	SLC26A8	solute carrier family 26,	NM_052961 ///	2.32491	TIA up vs Control
		member 8	NM_138718
220351_at	CCRL1	chemokine (C-C motif)	NM_016557 ///	2.32444	TIA up vs Control
		receptor-like 1	NM_178445
230964_at	FREM2	FRAS1 related	NM_207361	2.30984	TIA up vs Control
		extracellular matrix protein 2
231969_at	STOX2	storkhead box 2	NM_020225	2.2552	TIA up vs Control
1555367_at	ZNF479	zinc finger protein 479	NM_033273 ///	2.25193	TIA up vs Control
			XM_001714591 ///
			XM_001719979
1557717_at	LOC338862	hypothetical protein	—	2.22946	TIA up vs Control
		LOC338862
1554816_at	ASTN2	astrotactin 2	NM_014010 ///	2.22748	TIA up vs Control
			NM_198186 ///
			NM_198187 ///
			NM_198188
217487_x_at	FOLH1	folate hydrolase (prostate-	NM_001014986 ///	2.19987	TIA up vs Control
		specific membrane	NM_004476
		antigen) 1
241987_x_at	SNX31	sorting nexin 31	NM_152628	2.19167	TIA up vs Control
227250_at	KREMEN1	kringle containing	NM_001039570 ///	2.16406	TIA up vs Control
		transmembrane protein 1	NM_001039571
1555368_x_at	ZNF479	zinc finger protein 479	NM_033273 ///	2.16203	TIA up vs Control
			XM_001714591 ///
			XM_001719979
1563673_a_at	ALS2CR11	amyotrophic lateral	NM_152525	2.15177	TIA up vs Control
		sclerosis 2 (juvenile)
		chromosome region,
		candidate 11
239710_at	FIGN	fidgetin	NM_018086	2.14096	TIA up vs Control
242385_at	RORB	RAR-related orphan	NM_006914	2.14023	TIA up vs Control
		receptor B
1570009_at	LOC732096	similar to hCG2040240	XM_001720784 ///	2.13184	TIA up vs Control
			XM_001725388 ///
			XR_016064
1559520_at	GYPA	Glycophorin A	NM_002099	2.12904	TIA up vs Control
215783_s_at	ALPL	alkaline phosphatase,	NM_000478 ///	2.1006	TIA up vs Control
		liver/bone/kidney	NM_001127501
206140_at	LHX2	LIM homeobox 2	NM_004789	2.0959	TIA up vs Control
240390_at	GALNT5	UDP-N-acetyl-alpha-D-	NM_014568	2.09257	TIA up vs Control
		galactosamine:polypeptide
		N-
		acetylgalactosaminyltransferase
241961_at	SRD5A2L2	steroid 5 alpha-reductase	NM_001010874	2.08494	TIA up vs Control
		2-like 2
219271_at	GALNT14	UDP-N-acetyl-alpha-D-	NM_024572	2.07605	TIA up vs Control
		galactosamine:polypeptide
		N-
		acetylgalactosaminyltransferase
206048_at	OVOL2	ovo-like 2 (Drosophila)	NM_021220	2.06333	TIA up vs Control
242579_at	BMPR1B	bone morphogenetic	NM_001203	2.05687	TIA up vs Control
		protein receptor, type IB
226899_at	UNC5B	unc-5 homolog B (C. elegans)	NM_170744	2.04351	TIA up vs Control
231867_at	ODZ2	odz, odd Oz/ten-m	NM_001080428 ///	2.03143	TIA up vs Control
		homolog 2 (Drosophila)	NM_001122679
1557924_s_at	ALPL	alkaline phosphatase,	NM_000478 ///	2.02022	TIA up vs Control
		liver/bone/kidney	NM_001127501
217194_at	RASAL2	RAS protein activator like 2	NM_004841 ///	2.00632	TIA up vs Control
			NM_170692
207570_at	SHOX	short stature homeobox	NM_000451 ///	2.00103	TIA up vs Control
			NM_006883
235568_at	C19orf59	chromosome 19 open	NM_174918	1.99789	TIA up vs Control
		reading frame 59
1552946_at	ZNF114	zinc finger protein 114	NM_153608	1.99445	TIA up vs Control
1554473_at	SRGAP1	SLIT-ROBO Rho GTPase	NM_020762	1.99203	TIA up vs Control
		activating protein 1
228260_at	ELAVL2	ELAV (embryonic lethal,	NM_004432	1.9905	TIA up vs Control
		abnormal vision,
		Drosophila)-like 2 (Hu
		antigen B)
1559292_s_at	NCRNA00032	Clone IMAGE: 2275835	XM_376821 ///	1.98554	TIA up vs Control
		C9orf14 mRNA, partial	XM_938938
		sequence; alternatively
		spliced
214984_at	LOC440345	hypothetical protein	XR_015786	1.98536	TIA up vs Control
		LOC440345
1557155_a_at	FLJ30375	CDNA clone	XM_001724993 ///	1.97451	TIA up vs Control
		IMAGE: 5301781	XM_001725199 ///
			XM_001725628
215447_at	TFPI	Tissue factor pathway	NM_001032281 ///	1.96509	TIA up vs Control
		inhibitor (lipoprotein-	NM_006287
		associated coagulation
		inhibitor),
228825_at	PTGR1	prostaglandin reductase 1	NM_012212	1.95262	TIA up vs Control
213194_at	ROBO1	roundabout, axon guidance	NM_002941 ///	1.95207	TIA up vs Control
		receptor, homolog 1	NM_133631
		(Drosophila)
209119_x_at	NR2F2	nuclear receptor subfamily	NM_021005	1.94377	TIA up vs Control
		2, group F, member 2
206819_at	DKFZP434P211	POM121 membrane	NR_003714	1.93567	TIA up vs Control
		glycoprotein-like 1
		pseudogene
207235_s_at	GRM5	glutamate receptor,	NM_000842 ///	1.93451	TIA up vs Control
		metabotropic 5	NM_001143831
201744_s_at	LUM	lumican	NM_002345	1.93131	TIA up vs Control
230999_at	FLJ39051	CDNA FLJ39051 fis,	—	1.92605	TIA up vs Control
		clone NT2RP7011452
229218_at	COL1A2	collagen, type I, alpha 2	NM_000089	1.92067	TIA up vs Control
207500_at	CASP5	caspase 5, apoptosis-	NM_001136109 ///	1.91798	TIA up vs Control
		related cysteine peptidase	NM_001136110 ///
			NM_001136111 ///
			NM_001136112 ///
			NM_004347 //
214111_at	OPCML	opioid binding protein/cell	NM_001012393 ///	1.91158	TIA up vs Control
		adhesion molecule-like	NM_002545
1556666_a_at	TTC6	tetratricopeptide repeat	NM_001007795	1.91015	TIA up vs Control
		domain 6
214451_at	TFAP2B	transcription factor AP-2	NM_003221	1.89347	TIA up vs Control
		beta (activating enhancer
		binding protein 2 beta)
210262_at	CRISP2	cysteine-rich secretory	NM_001142407 ///	1.88349	TIA up vs Control
		protein 2	NM_001142408 ///
			NM_001142417 ///
			NM_001142435 ///
			NM_003296
204914_s_at	SOX11	SRY (sex determining	NM_003108	1.88201	TIA up vs Control
		region Y)-box 11
1562292_at	ANKRD30B	ankyrin repeat domain 30B	XM_001716904 ///	1.86641	TIA up vs Control
			XM_001717561 ///
			XM_001717810
227925_at	FLJ39051	CDNA FLJ39051 fis,	—	1.86433	TIA up vs Control
		clone NT2RP7011452
229057_at	SCN2A	sodium channel, voltage-	NM_001040142 ///	1.85129	TIA up vs Control
		gated, type II, alpha	NM_001040143 ///
		subunit	NM_021007
237510_at	MYNN	Myoneurin, mRNA	NM_018657	1.85041	TIA up vs Control
		(cDNA clone
		IMAGE: 4721583)
40284_at	FOXA2	forkhead box A2	NM_021784 ///	1.8498	TIA up vs Control
			NM_153675
233092_s_at	DKFZP434B061	DKFZP434B061 protein	XR_015528 ///	1.84946	TIA up vs Control
			XR_040812
230902_at	LOC645323	CDNA clone	NR_015436 ///	1.84336	TIA up vs Control
		IMAGE: 5260726	NR_024383 ///
			NR_024384 ///
			XR_041118 ///
			XR_041119 ///
			XR_041120
232547_at	SNIP	SNAP25-interacting	NM_025248	1.83841	TIA up vs Control
		protein
238850_at	LOC645323	hypothetical LOC645323	NR_015436 ///	1.81503	TIA up vs Control
			NR_024383 ///
			NR_024384 ///
			XR_041118 ///
			XR_041119 ///
			XR_041120
233879_at	LOC374491	TPTE and PTEN	NR_002815	1.81019	TIA up vs Control
		homologous inositol lipid
		phosphatase pseudogene
243520_x_at	ADAM30	ADAM metallopeptidase	NM_021794	1.80193	TIA up vs Control
		domain 30
206634_at	SIX3	SIX homeobox 3	NM_005413	1.78989	TIA up vs Control
1560790_at	FLJ36144	hypothetical protein	XR_040632 ///	1.78391	TIA up vs Control
		FLJ36144	XR_040633 ///
			XR_040634
232969_at	CARD8	caspase recruitment	NM_014959	1.78265	TIA up vs Control
		domain family, member 8
235370_at	KREMEN1	kringle containing	NM_001039570 ///	1.77475	TIA up vs Control
		transmembrane protein 1	NM_001039571
1555990_at	RP1-127L4.6	hypothetical protein	NM_001010859	1.76603	TIA up vs Control
		LOC150297
222291_at	FAM149A	family with sequence	NM_001006655 ///	1.75785	TIA up vs Control
		similarity 149, member A	NM_015398
239144_at	B3GAT2	beta-1,3-	NM_080742	1.75721	TIA up vs Control
		glucuronyltransferase 2
		(glucuronosyltransferase
		S)
235342_at	SPOCK3	sparc/osteonectin, cwcv	NM_001040159 ///	1.75314	TIA up vs Control
		and kazal-like domains	NM_016950
		proteoglycan (testican) 3
1553024_at	G30	protein LG30-like	—	1.75094	TIA up vs Control
214927_at	ITGBL1	integrin, beta-like 1 (with	NM_004791	1.73813	TIA up vs Control
		EGF-like repeat domains)
229538_s_at	IQGAP3	IQ motif containing	NM_178229	1.73797	TIA up vs Control
		GTPase activating protein 3
1553329_at	C7orf45	chromosome 7 open	NM_145268	1.72974	TIA up vs Control
		reading frame 45
232303_at	ZNF608	zinc finger protein 608	NM_020747	1.72629	TIA up vs Control
1558982_at	LOC375010	hypothetical LOC375010	XR_041271	1.72485	TIA up vs Control
230863_at	LRP2	low density lipoprotein-	NM_004525	1.71146	TIA up vs Control
		related protein 2
228121_at	TGFB2	transforming growth	NM_001135599 ///	1.70904	TIA up vs Control
		factor, beta 2	NM_003238
208443_x_at	SHOX2	short stature homeobox 2	NM_003030 ///	1.70616	TIA up vs Control
			NM_006884
206858_s_at	HOXC4 ///	homeobox C4 ///	NM_004503 ///	1.70414	TIA up vs Control
	HOXC6	homeobox C6	NM_014620 ///
			NM_153633 ///
			NM_153693
219134_at	ELTD1	EGF, latrophilin and seven	NM_022159	1.70282	TIA up vs Control
		transmembrane domain
		containing 1
222205_x_at	FAM182B ///	family with sequence	XM_001132551 ///	1.70042	TIA up vs Control
	RP13-401N8.2	similarity 182, member B	XM_001133521 ///
		/// hypothetical gene	XM_001718365 ///
		supported by	XM_933752
220696_at	PRO0478	PRO0478 protein	—	1.69169	TIA up vs Control
225571_at	LIFR	leukemia inhibitory factor	NM_001127671 ///	1.69168	TIA up vs Control
		receptor alpha	NM_002310
217483_at	FOLH1	folate hydrolase (prostate-	NM_001014986 ///	1.68955	TIA up vs Control
		specific membrane	NM_004476
		antigen) 1
232360_at	EHF	ets homologous factor	NM_012153	1.68951	TIA up vs Control
220429_at	NDST3	N-deacetylase/N-	NM_004784	1.68889	TIA up vs Control
		sulfotransferase (heparan
		glucosaminyl) 3
232416_at	BRUNOL5	bruno-like 5, RNA binding	NM_021938	1.68747	TIA up vs Control
		protein (Drosophila)
231434_at	LOC728460	similar to FLJ32921	XM_001128581 ///	1.68733	TIA up vs Control
		protein	XM_001129498 ///
			XM_001723364
208396_s_at	PDE1A	phosphodiesterase 1A,	NM_001003683 ///	1.68453	TIA up vs Control
		calmodulin-dependent	NM_005019
1569675_at	POU2AF1	POU class 2 associating	NM_006235	1.67876	TIA up vs Control
		factor 1, mRNA (cDNA
		clone MGC: 45211
		IMAGE: 5554134)
201579_at	FAT1	FAT tumor suppressor	NM_005245	1.67288	TIA up vs Control
		homolog 1 (Drosophila)
210292_s_at	PCDH11X ///	protocadherin 11 X-linked	NM_014522 ///	1.6605	TIA up vs Control
	PCDH11Y	/// protocadherin 11 Y-	NM_032967 ///
		linked	NM_032968 ///
			NM_032969 ///
			NM_032971 ///
			NM_032972
1558579_at	FLJ37786	hypothetical LOC642691	XR_041472 ///	1.66029	TIA up vs Control
			XR_041473
205896_at	SLC22A4	solute carrier family 22	NM_003059	1.65918	TIA up vs Control
		(organic
		cation/ergothioneine
		transporter), member 4
226121_at	DHRS13	dehydrogenase/reductase	NM_144683	1.65414	TIA up vs Control
		(SDR family) member 13
219850_s_at	EHF	ets homologous factor	NM_012153	1.64412	TIA up vs Control
235077_at	MEG3	maternally expressed 3	NR_002766 ///	1.6384	TIA up vs Control
		(non-protein coding)	NR_003530 ///
			NR_003531
214868_at	PIWIL1	piwi-like 1 (Drosophila)	NM_004764	1.63171	TIA up vs Control
232034_at	LOC203274	CDNA FLJ31544 fis,	—	1.63147	TIA up vs Control
		clone NT2RI2000865
1556704_s_at	LOC100133920	hypothetical protein	NR_024443 ///	1.63034	TIA up vs Control
	/// LOC286297	LOC100133920 ///	XM_001714612 ///
		hypothetical protein	XM_372109 ///
		LOC286297	XM_933054 ///
			XM_933058
220493_at	DMRT1	doublesex and mab-3	NM_021951	1.61917	TIA up vs Control
		related transcription factor 1
202912_at	ADM	adrenomedullin	NM_001124	1.61874	TIA up vs Control
1561200_at	VWA3B	von Willebrand factor A	NM_144992	1.61802	TIA up vs Control
		domain containing 3B
1555726_at	GAFA3	FGF-2 activity-associated	XM_001715321 ///	1.61768	TIA up vs Control
		protein 3	XM_001722922 ///
			XM_001723636
211267_at	HESX1	HESX homeobox 1	NM_003865	1.61355	TIA up vs Control
206134_at	ADAMDEC1	ADAM-like, decysin 1	NM_014479	1.61274	TIA up vs Control
203065_s_at	CAV1	caveolin 1, caveolae	NM_001753	1.60773	TIA up vs Control
		protein, 22 kDa
215516_at	LAMB4	laminin, beta 4	NM_007356	1.60646	TIA up vs Control
220205_at	TPTE	transmembrane	NM_199259 ///	1.60547	TIA up vs Control
		phosphatase with tensin	NM_199260 ///
		homology	NM_199261
1555462_at	PPP1R1C	protein phosphatase 1,	NM_001080545	1.60542	TIA up vs Control
		regulatory (inhibitor)
		subunit 1C
219403_s_at	HPSE	heparanase	NM_001098540 ///	1.60481	TIA up vs Control
			NM_006665
206513_at	AIM2	absent in melanoma 2	NM_004833	1.60396	TIA up vs Control
215321_at	RUNDC3B	RUN domain containing	NM_001134405 ///	1.60322	TIA up vs Control
		3B	NM_001134406 ///
			NM_138290
1552701_a_at	CARD16	caspase recruitment	NM_001017534 ///	1.59587	TIA up vs Control
		domain family, member 16	NM_052889
230519_at	FAM124A	family with sequence	NM_145019	1.59499	TIA up vs Control
		similarity 124A
240814_at	MGC39584	hypothetical gene	XR_017735 ///	1.59341	TIA up vs Control
		supported by BC029568	XR_017787 ///
			XR_041937
230170_at	OSM	oncostatin M	NM_020530	1.58899	TIA up vs Control
226872_at	RFX2	regulatory factor X, 2	NM_000635 ///	1.58786	TIA up vs Control
		(influences HLA class II	NM_134433
		expression)
214087_s_at	MYBPC1	myosin binding protein C,	NM_002465 ///	1.58609	TIA up vs Control
		slow type	NM_206819 ///
			NM_206820 ///
			NM_206821
203005_at	LTBR	lymphotoxin beta receptor	NM_002342	1.58399	TIA up vs Control
		(TNFR superfamily,
		member 3)
223977_s_at	C18orf2	chromosome 18 open	NM_031416 ///	1.58384	TIA up vs Control
		reading frame 2	NR_023925 ///
			NR_023926 ///
			NR_023927 ///
			NR_023928
240204_at	SNRPN	small nuclear	NM_003097 ///	1.58295	TIA up vs Control
		ribonucleoprotein	NM_022805 ///
		polypeptide N	NM_022806 ///
			NM_022807 ///
			NM_022808 ///
			NR_001289
229521_at	FLJ36031	hypothetical protein	NM_175884	1.58141	TIA up vs Control
		FLJ36031
205067_at	IL1B	interleukin 1, beta	NM_000576	1.57884	TIA up vs Control
206479_at	TRPM1	transient receptor potential	NM_002420	1.57541	TIA up vs Control
		cation channel, subfamily
		M, member 1
1553931_at	OSTCL	oligosaccharyltransferase	NM_145303	1.57501	TIA up vs Control
		complex subunit-like
210449_x_at	MAPK14	mitogen-activated protein	NM_001315 ///	1.57327	TIA up vs Control
		kinase 14	NM_139012 ///
			NM_139013 ///
			NM_139014
238428_at	KCNJ15 ///	potassium inwardly-	NM_002243 ///	1.56965	TIA up vs Control
	LOC100131955	rectifying channel,	NM_170736 ///
		subfamily J, member 15 ///	NM_170737 ///
		similar to pot	XM_001713900 ///
			XM_001715532 ///
			XM_0
238964_at	FIGN	fidgetin	NM_018086	1.56796	TIA up vs Control
227566_at	HNT	neurotrimin	NM_001048209 ///	1.56554	TIA up vs Control
			NM_016522
205863_at	S100A12	S100 calcium binding	NM_005621	1.5633	TIA up vs Control
		protein A12
208168_s_at	CHIT1	chitinase 1	NM_003465	1.56138	TIA up vs Control
		(chitotriosidase)
239203_at	C7orf53	chromosome 7 open	NM_001134468 ///	1.55912	TIA up vs Control
		reading frame 53	NM_182597
1569025_s_at	FAM13A1	family with sequence	NM_001015045 ///	1.55876	TIA up vs Control
		similarity 13, member A1	NM_014883
204763_s_at	GNAO1	guanine nucleotide binding	NM_020988 ///	1.5542	TIA up vs Control
		protein (G protein), alpha	NM_138736
		activating activity polype
211561_x_at	MAPK14	mitogen-activated protein	NM_001315 ///	1.55337	TIA up vs Control
		kinase 14	NM_139012 ///
			NM_139013 ///
			NM_139014
220645_at	FAM55D	family with sequence	NM_001077639 ///	1.55166	TIA up vs Control
		similarity 55, member D	NM_017678
241669_x_at	PRKD2	protein kinase D2	NM_001079880 ///	1.55139	TIA up vs Control
			NM_001079881 ///
			NM_001079882 ///
			NM_016457
210582_s_at	LIMK2	LIM domain kinase 2	NM_001031801 ///	1.5485	TIA up vs Control
			NM_005569 ///
			NM_016733
1553652_a_at	C18orf54	chromosome 18 open	NM_173529	1.54796	TIA up vs Control
		reading frame 54
211959_at	IGFBP5	insulin-like growth factor	NM_000599	1.54545	TIA up vs Control
		binding protein 5
243277_x_at	EVI1	ecotropic viral integration	NM_001105077 ///	1.5445	TIA up vs Control
		site 1	NM_001105078 ///
			NM_005241
202446_s_at	PLSCR1	phospholipid scramblase 1	NM_021105	1.54059	TIA up vs Control
1553613_s_at	FOXC1	forkhead box C1	NM_001453	1.53964	TIA up vs Control
1568933_at	LOC646627	phospholipase inhibitor	NM_001085474	1.53874	TIA up vs Control
244007_at	ZNF462	zinc finger protein 462	NM_021224	1.53545	TIA up vs Control
239989_at	CNTLN	centlein, centrosomal	NM_001114395 ///	1.53478	TIA up vs Control
		protein	NM_017738
229743_at	ZNF438	zinc finger protein 438	NM_001143766 ///	1.53049	TIA up vs Control
			NM_001143767 ///
			NM_001143768 ///
			NM_001143769 ///
			NM_001143770
1553002_at	DEFB105A ///	defensin, beta 105A ///	NM_001040703 ///	1.52948	TIA up vs Control
	DEFB105B	defensin, beta 105B	NM_152250
1560823_at	LOC340017	hypothetical protein	—	1.51946	TIA up vs Control
		LOC340017
1554540_at	C1orf67	chromosome 1 open	NM_144989	1.51941	TIA up vs Control
		reading frame 67
207275_s_at	ACSL1	acyl-CoA synthetase long-	NM_001995	1.51866	TIA up vs Control
		chain family member 1
209614_at	ADH1B	alcohol dehydrogenase 1B	NM_000668	1.51397	TIA up vs Control
		(class I), beta polypeptide
216236_s_at	SLC2A14 ///	solute carrier family 2	NM_006931 ///	1.51356	TIA up vs Control
	SLC2A3	(facilitated glucose	NM_153449
		transporter), member 14 ///
		solute
39402_at	IL1B	interleukin 1, beta	NM_000576	1.51316	TIA up vs Control
203759_at	ST3GAL4	ST3 beta-galactoside	NM_006278 ///	1.51002	TIA up vs Control
		alpha-2,3-sialyltransferase 4	XM_001714343 ///
			XM_001726541 ///
			XM_001726562
222435_s_at	UBE2J1	ubiquitin-conjugating	NM_016021	1.50758	TIA up vs Control
		enzyme E2, J1 (UBC6
		homolog, yeast)
233030_at	PNPLA3	patatin-like phospholipase	NM_025225	1.50269	TIA up vs Control
		domain containing 3
1559400_s_at	PAPPA	pregnancy-associated	NM_002581	1.50009	TIA up vs Control
		plasma protein A,
		pappalysin 1

Underexpressed biomarkers indicative of the occurrence of TIA or useful to predict the risk of experiencing TIA are listed in Table 2. In practicing the present methods, the expression levels of a plurality of biomarkers from Table 2 are determined, optionally in combination with other TIA-associated biomarkers described herein (e.g., in Tables 1, 5A, 5B, 5C, 5D, 7, 8 and/or 9) and known in the art. In some embodiments, the expression levels of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 45, 50, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more, biomarkers listed in Table 2 are determined, optionally in combination with other TIA-associated biomarkers described herein (e.g., in Tables 1, 5A, 5B, 5C, 5D, 7, 8 and/or 9) and known in the art.
In patients who have experienced TIA or who are at risk of developing TIA, the biomarkers of Table 2 are underexpressed in comparison to a control level of expression. A control level of expression can refer to the level of expression of the same biomarker in an individual who has not had and is not at risk for a vascular event or the level of expression of a stably expressed endogenous control gene. In patients who have experienced TIA or who are at risk of developing TIA, the biomarkers of Table 2 are underexpressed at least 1.5-fold, e.g., at least 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2.0-fold, 2.1-fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3.0-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold or 3.5-fold, or more, in comparison to a control level of expression.

TABLE 2

TIA-associated biomarkers that are downregulated

242191_at	NBPF10 ///	neuroblastoma breakpoint	NM_001039703 ///	−1.50043	TIA down vs
	RP11-94I2.2	family, member 10 ///	NM_183372 ///		Control
		hypothetical protein	XM_001722184
		LOC200030
232055_at	SFXN1	sideroflexin 1	NM_022754	−1.50117	TIA down vs
					Control
1555883_s_at	SPIN3	spindlin family, member 3	NM_001010862	−1.50348	TIA down vs
					Control
206487_at	UNC84A	unc-84 homolog A (C. elegans)	NM_001130965 ///	−1.50376	TIA down vs
			NM_025154		Control
223601_at	OLFM2	olfactomedin 2	NM_058164	−1.5119	TIA down vs
					Control
244011_at	PPM1K	protein phosphatase 1K	NM_152542	−1.51501	TIA down vs
		(PP2C domain containing)			Control
214615_at	P2RY10	purinergic receptor P2Y,	NM_014499 ///	−1.51779	TIA down vs
		G-protein coupled, 10	NM_198333		Control
55872_at	ZNF512B	zinc finger protein 512B	NM_020713	−1.52158	TIA down vs
					Control
243857_at	MORF4L2	Mrgx mRNA for MRGX	NM_001142418 ///	−1.52328	TIA down vs
			NM_001142419 ///		Control
			NM_001142420 ///
			NM_001142421 ///
			NM_001142422
1560133_at	GIGYF2	GRB10 interacting GYF	NM_001103146 ///	−1.52626	TIA down vs
		protein 2	NM_001103147 ///		Control
			NM_001103148 ///
			NM_015575
1554273_a_at	ERAP2	endoplasmic reticulum	NM_001130140 ///	−1.52883	TIA down vs
		aminopeptidase 2	NM_022350		Control
1553423_a_at	SLFN13	schlafen family member 13	NM_144682	−1.53028	TIA down vs
					Control
229094_at	LOC401431	hypothetical gene	XR_040272 ///	−1.53069	TIA down vs
		LOC401431	XR_040273 ///		Control
			XR_040274 ///
			XR_040275
207078_at	MED6	mediator complex subunit 6	NM_005466	−1.53192	TIA down vs
					Control
227372_s_at	BAIAP2L1 ///	BAI1-associated protein 2-	NM_018842 ///	−1.53271	TIA down vs
	LOC100128461	like 1 /// hypothetical	XM_001722656 ///		Control
		protein LOC100128461	XM_001724217 ///
			XM_001724858
236728_at	LNPEP	leucyl/cystinyl	NM_005575 ///	−1.53387	TIA down vs
		aminopeptidase	NM_175920		Control
215663_at	MBNL1	muscleblind-like	NM_021038 ///	−1.53726	TIA down vs
		(Drosophila)	NM_207292 ///		Control
			NM_207293 ///
			NM_207294 ///
			NM_207295 ///
			NM_207296
229093_at	NOS3	nitric oxide synthase 3	NM_000603	−1.53818	TIA down vs
		(endothelial cell)			Control
212935_at	MCF2L	MCF.2 cell line derived	NM_001112732 ///	−1.53863	TIA down vs
		transforming sequence-like	NM_024979		Control
215750_at	KIAA1659	KIAA1659 protein	XM_001723799 ///	−1.54646	TIA down vs
			XM_001725435 ///		Control
			XM_001726785
212699_at	SCAMP5	secretory carrier	NM_138967	−1.54948	TIA down vs
		membrane protein 5			Control
1565911_at	LOC648921	MRNA full length insert	XM_001715629 ///	−1.54981	TIA down vs
		cDNA clone	XM_001720571 ///		Control
		EUROIMAGE 209544	XR_018520
239651_at	ANAPC5	anaphase promoting	NM_001137559 ///	−1.55844	TIA down vs
		complex subunit 5	NM_016237		Control
213993_at	SPON1	spondin 1, extracellular	NM_006108	−1.55928	TIA down vs
		matrix protein			Control
231108_at	FUS	fusion (involved in	NM_004960	−1.56277	TIA down vs
		t(12; 16) in malignant			Control
		liposarcoma)
221288_at	GPR22	G protein-coupled receptor	NM_005295	−1.56303	TIA down vs
		22			Control
219815_at	GAL3ST4	galactose-3-O-	NM_024637	−1.5674	TIA down vs
		sulfotransferase 4			Control
242111_at	METTL3	methyltransferase like 3	NM_019852	−1.56742	TIA down vs
					Control
239062_at	LOC100131096	hypothetical	XM_001720907 ///	−1.57675	TIA down vs
		LOC100131096	XM_001726205 ///		Control
			XM_001726705
230792_at	FAAH2	fatty acid amide hydrolase 2	NM_174912	−1.57807	TIA down vs
					Control
232020_at	SMURF2	SMAD specific E3	NM_022739	−1.57992	TIA down vs
		ubiquitin protein ligase 2			Control
226587_at	SNRPN	small nuclear	NM_003097 ///	−1.58006	TIA down vs
		ribonucleoprotein	NM_022805 ///		Control
		polypeptide N	NM_022806 ///
			NM_022807 ///
			NM_022808 ///
			NR_001289
229247_at	FBLN7	fibulin 7	NM_001128165 ///	−1.58734	TIA down vs
			NM_153214		Control
223080_at	GLS	Glutaminase, mRNA	NM_014905	−1.59404	TIA down vs
		(cDNA clone MGC: 33744			Control
		IMAGE: 5263220)
1557350_at	G3BP1	GTPase activating protein	NM_005754 ///	−1.6194	TIA down vs
		(SH3 domain) binding	NM_198395		Control
		protein 1
219864_s_at	RCAN3	RCAN family member 3	NM_013441	−1.61977	TIA down vs
					Control
209368_at	EPHX2	epoxide hydrolase 2,	NM_001979	−1.62474	TIA down vs
		cytoplasmic			Control
212504_at	DIP2C	DIP2 disco-interacting	NM_014974	−1.62614	TIA down vs
		protein 2 homolog C			Control
		(Drosophila)
1553645_at	CCDC141	coiled-coil domain	NM_173648	−1.62867	TIA down vs
		containing 141			Control
239871_at	CLTC	Clathrin, heavy chain (Hc),	NM_004859	−1.63031	TIA down vs
		mRNA (cDNA clone			Control
		IMAGE: 4812912)
202768_at	FOSB	FBJ murine osteosarcoma	NM_001114171 ///	−1.63049	TIA down vs
		viral oncogene homolog B	NM_006732		Control
221631_at	CACNA1I	calcium channel, voltage-	NM_001003406 ///	−1.63297	TIA down vs
		dependent, T type, alpha 1I	NM_021096		Control
		subunit
1558569_at	UNQ6228	MRNA; cDNA	XM_001725293 ///	−1.63796	TIA down vs
		DKFZp667K1619 (from	XM_001725359 ///		Control
		clone DKFZp667K1619)	XM_001726164
229252_at	ATG9B	ATG9 autophagy related 9	NM_173681	−1.64694	TIA down vs
		homolog B (S. cerevisiae)			Control
222862_s_at	AK5	adenylate kinase 5	NM_012093 ///	−1.64741	TIA down vs
			NM_174858		Control
1555882_at	SPIN3	spindlin family, member 3	NM_001010862	−1.65127	TIA down vs
					Control
239635_at	RBM14	RNA binding motif protein	NM_006328	−1.65349	TIA down vs
		14			Control
1560741_at	SNRPN	small nuclear	NM_003097 ///	−1.65945	TIA down vs
		ribonucleoprotein	NM_022805 ///		Control
		polypeptide N	NM_022806 ///
			NM_022807 ///
			NM_022808 ///
			NR_001289
214180_at	MAN1C1	mannosidase, alpha, class	NM_020379	−1.66631	TIA down vs
		1C, member 1			Control
220085_at	HELLS	helicase, lymphoid-	NM_018063	−1.67692	TIA down vs
		specific			Control
220048_at	EDAR	ectodysplasin A receptor	NM_022336	−1.69385	TIA down vs
					Control
239667_at	SLC3A1	solute carrier family 3	NM_000341	−1.69708	TIA down vs
		(cystine, dibasic and			Control
		neutral amino acid
		transporters, a
1568873_at	ZNF519	zinc finger protein 519	NM_145287	−1.70283	TIA down vs
					Control
236621_at	LOC100130070 ///	similar to	NM_001030 ///	−1.70558	TIA down vs
	LOC100130775 ///	metallopanstimulin ///	XM_001721002 ///		Control
	LOC100131787 ///	similar to rCG63653 ///	XM_001722161 ///
	LOC100131905 ///	similar to metallopans	XM_001722965 ///
	LOC100132291 ///		XM_001723889 //
	LOC100132488 ///
	RPS27
229234_at	ZC3H12B	zinc finger CCCH-type	NM_001010888	−1.72127	TIA down vs
		containing 12B			Control
241723_at	IQGAP2	IQ motif containing	NM_006633	−1.73571	TIA down vs
		GTPase activating protein 2			Control
226913_s_at	SOX8	SRY (sex determining	NM_014587	−1.73755	TIA down vs
		region Y)-box 8			Control
1557450_s_at	WHDC1L2	WAS protein homology	XM_926785	−1.75555	TIA down vs
		region 2 domain			Control
		containing 1-like 2
1556116_s_at	TNPO1	Transportin 1, mRNA	NM_002270 ///	−1.7577	TIA down vs
		(cDNA clone MGC: 17116	NM_153188		Control
		IMAGE: 4178989)
218856_at	TNFRSF21	tumor necrosis factor	NM_014452	−1.77712	TIA down vs
		receptor superfamily,			Control
		member 21
244521_at	TSHZ2	Cell growth-inhibiting	NM_173485	−1.86192	TIA down vs
		protein 7			Control
1553998_at	DMRTC1 ///	DMRT-like family C1 ///	NM_001080851 ///	−1.86704	TIA down vs
	DMRTC1B	DMRT-like family C1B	NM_033053		Control
204550_x_at	GSTM1	glutathione S-transferase	NM_000561 ///	−1.95136	TIA down vs
		mu 1	NM_146421		Control
219308_s_at	AK5	adenylate kinase 5	NM_012093 ///	−1.95614	TIA down vs
			NM_174858		Control
204418_x_at	GSTM2	glutathione S-transferase	NM_000848 ///	−1.95729	TIA down vs
		mu 2 (muscle)	NM_001142368		Control
235758_at	PNMA6A	paraneoplastic antigen like	NM_032882	−1.95731	TIA down vs
		6A			Control
239771_at	CAND1	cullin-associated and	NM_018448	−1.97531	TIA down vs
		neddylation-dissociated 1			Control
1562028_at	CCND3	Cyclin D3 (CCND3),	NM_001136017 ///	−2.00377	TIA down vs
		transcript variant 3, mRNA	NM_001136125 ///		Control
			NM_001136126 ///
			NM_001760
215333_x_at	GSTM1	glutathione S-transferase	NM_000561 ///	−2.03103	TIA down vs
		mu 1	NM_146421		Control
232207_at	GUSBL2	glucuronidase, beta-like 2	NR_003660 ///	−2.10621	TIA down vs
			XR_042150 ///		Control
			XR_042151

4. Comparison to a Control Level of Expression

The expression of the TIA-associated biomarkers are compared to a control level of expression. As appropriate, the control level of expression can be the expression level of the same TIA-associated biomarker in an otherwise healthy individual (e.g., in an individual who has not experienced and/or is not at risk of experiencing TIA). In some embodiments, the control level of expression is the expression level of a plurality of stably expressed endogenous reference biomarkers, as described herein or known in the art. In some embodiments, the control level of expression is a predetermined threshold level of expression of the same TIA-associated biomarker, e.g., based on the expression level of the biomarker in a population of otherwise healthy individuals. In some embodiments, the expression level of the TIA-associated biomarker and the TIA-associated biomarker in an otherwise healthy individual are normalized to (i.e., divided by), e.g., the expression levels of a plurality of stably expressed endogenous reference biomarkers.
In some embodiments, the overexpression or underexpression of a TIA-associated biomarker is determined with reference to the expression of the same TIA-associated biomarker in an otherwise healthy individual. For example, a healthy or normal control individual has not experienced and/or is not at risk of experiencing TIA. The healthy or normal control individual generally has not experienced a vascular event (e.g., TIA, ischemic stroke, myocardial infarction, peripheral vascular disease, or venous thromboembolism). The healthy or normal control individual generally does not have one or more vascular risk factors (e.g., hypertension, diabetes mellitus, hyperlipidemia, or tobacco smoking) As appropriate, the expression levels of the target TIA-associated biomarker in the healthy or normal control individual can be normalized (i.e., divided by) the expression levels of a plurality of stably expressed endogenous reference biomarkers.
In some embodiments, the overexpression or underexpression of a TIA-associated biomarker is determined with reference to one or more stably expressed endogenous reference biomarkers. Internal control biomarkers or endogenous reference biomarkers are expressed at the same or nearly the same expression levels in the blood of patients with stroke or TIAs as compared to control patients. Target biomarkers are expressed at higher or lower levels in the blood of the stroke or TIA patients. The expression levels of the target biomarker to the reference biomarker are normalized by dividing the expression level of the target biomarker to the expression levels of a plurality of endogenous reference biomarkers. The normalized expression level of a target biomarker can be used to predict the occurrence or lack thereof of stroke or TIA, and/or the cause of stroke or TIA.
In some embodiments, the expression level of the TIA-associated biomarker from a patient suspected of having or experiencing TIA and from a control patient are normalized with respect to the expression levels of a plurality of stably expressed endogenous. The expression levels of the normalized expression of the TIA-associated biomarker is compared to the expression levels of the normalized expression of the same TIA-associated biomarker in a control patient. The determined fold change in expression=normalized expression of target biomarker in TIA patient/normalized expression of target biomarker in control patient. Overexpression or underexpression of the normalized TIA-associated biomarker in the TIA patient by at least about 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2.0-fold, 2.1 fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3.0-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold or 3.5-fold, or more, in comparison to the expression levels of the normalized TIA-associated biomarker in a healthy control patient indicates that the TIA patient has experienced or is at risk of experiencing TIA.
In some embodiments, the control level of expression is a predetermined threshold level. The threshold level can correspond to the level of expression of the same TIA-associated biomarker in an otherwise healthy individual or a population of otherwise healthy individuals, optionally normalized to the expression levels of a plurality of endogenous reference biomarkers. After expression levels and normalized expression levels of the TIA-associated biomarkers are determined in a representative number of otherwise healthy individuals and individuals predisposed to experiencing TIA, normal and TIA expression levels of the TIA-associated biomarkers can be maintained in a database, allowing for determination of threshold expression levels indicative of the presence or absence of risk to experience TIA or the occurrence of TIA. If the predetermined threshold level of expression is with respect to a population of normal control patients, then overexpression or underexpression of the TIA-associated biomarker (usually normalized) in the TIA patient by at least about 1.2-fold, 1.3-fold, 1.4-fold, 1.5-fold, 1.6-fold, 1.7-fold, 1.8-fold, 1.9-fold, 2.0-fold, 2.1 fold, 2.2-fold, 2.3-fold, 2.4-fold, 2.5-fold, 2.6-fold, 2.7-fold, 2.8-fold, 2.9-fold, 3.0-fold, 3.1-fold, 3.2-fold, 3.3-fold, 3.4-fold or 3.5-fold, or more, in comparison to the threshold level indicates that the TIA patient has experienced or is at risk of experiencing TIA. If the predetermined threshold level of expression is with respect to a population of patients known to have experienced TIA or known to be at risk for experiencing TIA, then an expression level in the patient suspected of experiencing TIA that is approximately equal to the threshold level (or overexpressed or underexpressed greater than the threshold level of expression), indicates that the TIA patient has experienced or is at risk of experiencing TIA.
With respect to the endogenous reference biomarkers used for comparison, preferably, the endogenous reference biomarkers are stably expressed in blood. Exemplary endogenous reference biomarkers that find use are listed in Table 3, below. Further suitable endogenous reference biomarkers are published, e.g., in Stamova, et al., BMC Medical Genomics (2009) 2:49. In some embodiments, the expression levels of a plurality of endogenous reference biomarkers are determined as a control. In some embodiments, the expression levels of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, or more, endogenous reference biomarkers, e.g., as listed in Table 3 or known in the art, are determined as a control.
In some embodiments, the expression levels of the endogenous reference biomarkers GAPDH, ACTB, B2M, HMBS and PPIB are determined as a control. In some embodiments, the expression levels of 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or more, endogenous reference biomarkers selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4 KB, CRTC1, HADHA, MAP1LC3B, KAT5, CDC2L1///CDC2L2, GTSE1, CDC2L1///CDC2L2, TCF25, CHP, LRRC40, hCG 2003956/1/LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHC5, C9orf23, LRRC45, NACC1, LOC100133445///LOC115110, PEX16 are determined as a control.

TABLE 3

The 38 endogenous reference biomarkers stably expressed
in blood for use in normalization and as control levels.
Table 3 - Stably Expressed Endogenous Reference Biomarkers

					RefSeq	RefSeq Protein
Probe Set ID	Gene Symbol	Gene Title	GenBank ID	UniGene ID	Transcript ID	ID

201499_s_at	USP7	ubiquitin specific peptidase	NM_003470.1	Hs.706830	NM_003470	NP_003461
		7 (herpes virus-
		associated)
202501_at	MAPRE2	microtubule-associated	NM_014268.1	Hs.532824	NM_001143826 ///	NP_001137298 ///
		protein, RP/EB family,			NM_001143827 ///	NP_001137299 ///
		member 2			NM_014268 ///	NP_055083
					NR_026570
202573_at	CSNK1G2	casein kinase 1, gamma 2	AL530441	Hs.651905	NM_001319	NP_001310
203280_at	SAFB2	scaffold attachment factor	NM_014649.1	Hs.655392	NM_014649	NP_055464
		B2
204842_x_at	PRKAR2A	protein kinase, cAMP-	BC002763.1	Hs.631923	NM_004157	NP_004148
		dependent, regulatory,
		type II, alpha
206138_s_at	PI4KB	phosphatidylinositol 4-	NM_002651.1	Hs.632465	NM_002651	NP_002642
		kinase, catalytic, beta
207159_x_at	CRTC1	CREB regulated	NM_025021.1	Hs.371096	NM_001098482 ///	NP_001091952 ///
		transcription coactivator 1			NM_015321	NP_056136
208630_at	HADHA	hydroxyacyl-Coenzyme A	AI972144	Hs.516032	NM_000182	NP_000173
		dehydrogenase/3-
		ketoacyl-Coenzyme A
		thiolase/enoyl-Coenzyme
		A hydratase (trifunctional
		protein), alpha subunit
208786_s_at	MAP1LC3B	microtubule-associated	AF183417.1	Hs.356061	NM_022818	NP_073729
		protein 1 light chain 3 beta
209192_x_at	KAT5	K(lysine) acetyltransferase	BC000166.2	Hs.397010	NM_006388 ///	NP_006379 ///
		5			NM_182709 ///	NP_874368 ///
					NM_182710	NP_874369
210474_s_at	CDC2L1 ///	cell division cycle 2-like 1	U04819.1	Hs.651228	NM_024011 ///	NP_076916 ///
	CDC2L2	(PITSLRE proteins) /// cell			NM_033486 ///	NP_277021 ///
		division cycle 2-like 2			NM_033487 ///	NP_277022 ///
		(PITSLRE proteins)			NM_033488 ///	NP_277023 ///
					NM_033489 ///	NP_277024 ///
					NM_033492 ///	NP_277027 ///
					NM_033493 ///	NP_277028 ///
					NM_033529	NP_277071
211040_x_at	GTSE1	G-2 and S-phase	BC006325.1	Hs.386189	NM_016426	NP_057510
		expressed 1
211289_x_at	CDC2L1 ///	cell division cycle 2-like 1	AF067524.1	Hs.651228	NM_024011 ///	NP_076916 ///
	CDC2L2	(PITSLRE proteins) /// cell			NM_033486 ///	NP_277021 ///
		division cycle 2-like 2			NM_033487 ///	NP_277022 ///
		(PITSLRE proteins)			NM_033488 ///	NP_277023 ///
					NM_033489 ///	NP_277024 ///
					NM_033492 ///	NP_277027 ///
					NM_033493 ///	NP_277028 ///
					NM_033529	NP_277071
213311_s_at	TCF25	transcription factor 25	BF000251	Hs.415342	NM_014972	NP_055787
		(basic helix-loop-helix)
214665_s_at	CHP	calcium binding protein	AK000095.1	Hs.406234	NM_007236	NP_009167
		P22
215063_x_at	LRRC40	leucine rich repeat	AL390149.1	Hs.147836	NM_017768	NP_060238
		containing 40
215200_x_at	—	—	AK022362.1	Hs.663419	—	—
215568_x_at	hCG_2003956 ///	hCG2003956 ///	AL031295	Hs.533479	NM_007260 ///	NP_009191
	LYPLA2 ///	lysophospholipase II ///			NR_001444
	LYPLA2P1	lysophospholipase II
		pseudogene 1
216038_x_at	DAXX	death-domain associated	BE965715	Hs.336916	NM_001141969 ///	NP_001135441 ///
		protein			NM_001141970 ///	NP_001135442 ///
					NM_001350 ///	NP_001341
					NR_024517
217393_x_at	UBE2NL	ubiquitin-conjugating	AL109622	Hs.585177	NM_001012989	NP_001013007
		enzyme E2N-like
217549_at	—	—	AW574933	Hs.527860	—	—
217672_x_at	EIF1	eukaryotic translation	BF114906	Hs.150580	NM_005801	NP_005792
		initiation factor 1
217938_s_at	KCMF1	potassium channel	NM_020122.1	Hs.654968	NM_020122	NP_064507
		modulatory factor 1
218378_s_at	PRKRIP1	PRKR interacting protein 1	NM_024653.1	Hs.406395	NM_024653	NP_078929
		(IL11 inducible)
218571_s_at	CHMP4A	chromatin modifying	NM_014169.1	Hs.279761	NM_014169	NP_054888
		protein 4A
219074_at	TMEM184C	transmembrane protein	NM_018241.1	Hs.203896	NM_018241	NP_060711
		184C
220052_s_at	TINF2	TERF1 (TRF1)-interacting	NM_012461.1	Hs.496191	NM_001099274 ///	NP_001092744 ///
		nuclear factor 2			NM_012461	NP_036593
22041 1_x_at	PODNL1	podocan-like 1	NM_024825.1	Hs.448497	NM_001146254 ///	NP_001139726 ///
					NM_001146255 ///	NP_001139727 ///
					NM_024825	NP_079101
221813_at	FBXO42	F-box protein 42	AI129395	Hs.522384	NM_018994	NP_061867
222207_x_at	LOC441258	Williams Beuren syndrome	AK024602.1	Hs.711232	—	—
		chromosome region 19
		pseudogene
222733_x_at	RRP1	ribosomal RNA processing	BC000380.1	Hs.110757	NM_003683	NP_003674
		1 homolog (S. cerevisiae)
224667_x_at	C10orf104	chromosome 10 open	AK023981.1	Hs.426296	NM_173473	NP_775744
		reading frame 104
224858_at	ZDHHC5	zinc finger, DHHC-type	AK023130.1	Hs.27239	NM_015457	NP_056272
		containing 5
225403_at	C9orf23	chromosome 9 open	AL528391	Hs.15961	NM_148178 ///	NP_680544 ///
		reading frame 23			NM_148179	NP_680545
226253_at	LRRC45	leucine rich repeat	BE965418	Hs.143774	NM_144999	NP_659436
		containing 45
227651_at	NACC1	nucleus accumbens	AI498126	Hs.531614	NM_052876	NP_443108
		associated 1, BEN and
		BTB (POZ) domain
		containing
232190_x_at	LOC100133445 ///	hypothetical	AI393958	Hs.132272	NR_026927 ///	—
	LOC115110	LOC100133445 ///			XR_036887 ///
		hypothetical protein			XR_038144
		LOC115110
49878_at	PEX16	peroxisomal biogenesis	AA523441	Hs.100915	NM_004813 ///	NP_004804 ///
		factor 16			NM_057174	NP_476515

5. Methods of Determining the Cause of TIA

Subsets of the TIA-associated biomarkers described herein further find use in predicting or determining the cause of TIA.
For example, patients that overexpress genes involved in extracellular matrix remodeling including one or more or all genes selected from MMP16, MMP19, MMP26, COL1A1, COL1A2, COL3A1, COL10A1, COL11A1, COL25A1, COL27A1, FGFs and EGFR may have atherosclerosis.
Individuals can have a risk or predisposition to experiencing TIA, e.g., based on genetics, a related disease condition, environment or lifestyle. For example, in some embodiments, the patient suffers from a chronic inflammatory condition, e.g., has an autoimmune disease (e.g., rheumatoid arthritis, Crohn's disease inflammatory bowel disease), atherosclerosis, hypertension, or diabetes. In some embodiments, the patient has high LDL-cholesterol levels or suffers from a cardiovascular disease (e.g., atherosclerosis, coronary artery disease). In some embodiments, the patient has an endocrine system disorder, a neurodegenerative disorder, a connective tissue disorder, or a skeletal and muscular disorder. Exemplary disorders associated with, related to, or causative of TIA are provided in Table 7.
In some embodiments, the patient may have a neurological disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADH1B, AK5, ANXA3, APBA2, ASTN2 (includes EG:23245), BCL6, BMPR1B, CASP5, CAV1, CNTN4, DIP2C, ELAVL2, EPHX2, ERAP2, FAM124A, FAM13A, FAM149A, FAT1, FOLH1, FOXC1, GABRB2, GIGYF2, GNAO1, GRM5, GSTM1, HESX1, HOXC6, IGFBP5, IL1B, IQGAP2, ITGBL1, LAMB4, LIFR, LTBR, MECOM, NBPF10, NDST3, NELL2, NOS3, NTM, ODZ2, OLFM2, OPCML, PDE1A, RFX2, ROBO1, S100A12, SCN2A, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SOX9, SPOCK3, SPON1, TGFB2, TLR5, TNFRSF21, TRPM1, TSHZ2, TTC6 (includes EG:115669), UNC5B, UNC84A and ZNF608.
In some embodiments, the patient may have a skeletal or muscular disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ASTN2 (includes EG:23245), BCL6, BMPR1B, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A1, COL1A2, DIP2C, DNAH14, EDAR, ELAVL2, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, GIGYF2, GNAO1, HOXC6, IL1B, KCNJ15, LAMB4, LIFR, LTBR, LUM, MAPK14, MYBPC1, NOS3, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SCN2A, SHOX, SLC22A4 (includes EG:6583), SOX9, SPOCK3, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), TWIST1, UNC5B, VWA3B and ZNF438.
In some embodiments, the patient may have an inflammatory disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ANXA3, APBA2, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CAV1, CCND3, CCRL1, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, ERAP2, FAM124A, FBLN7, FOSB, FREM2, GABRB2, GRM5, IL1B, KCNJ15, LAMB4, LHX2, LNPEP, LRP2, LTBR, LUM, MAPK14, MECOM, MYBPC1, NOS3, ODZ2, OPCML, OSM, PAPPA, PDE1A, PPP1R1C, ROBOT, RUNDC3B, S100A12, SCN2A, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SMURF2, SNRPN, SPON1, TGFB2, TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), TWIST1, UNC5B, VWA3B and ZNF438.
In some embodiments, the patient may have a cardiovascular disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ALPL, ASTN2 (includes EG:23245), BCL6, BMPR1B, C18ORF54, CACNA1I, CARD16, CAV1, CNTN4, DMRT1, DNAH14, EDAR, EPHX2, ERAP2, FAM13A, FOLH1, FOSB, FREM2, GABRB2, GRM5, GSTM1, IL1B, IQGAP2, LIFR, LTBR, MAN1C1, MAPK14, MBNL1, MCF2L, MECOM, MYBPC1, NOS3, NTM, ODZ2, OLFM2, OPCML, PAPPA, PDE1A, ROBO1, RORB, S100A12, SMURF2, SNRPN, SOX9, SPOCK3, SPON1, TFPI, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have an immunological disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ANXA3, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CCRL1, CLTC, CNTN4, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FAT1, FOSB, GABRB2, GOLGA6L2, GSTM1, GUSBL2, IL1B, IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14, MYBPC1, NELL2, NOS3, NTM, ODZ2, OPCML, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), SNRPN, SPON1, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have a metabolic disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, EPHX2, FAT1, FOXA2, GABRB2, GUSBL2, IGFBP5, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have an endocrine system disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2, GUSBL2, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SHOX, SLC22A4 (includes EG:6583), SLC2A3, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have an autoimmune disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, AK5, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, GUSBL2, IL1B, IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14, MYBPC1, NELL2, ODZ2, OPCML, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), SNRPN, SPON1, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have diabetes and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2, GUSBL2, IL1B, IQGAP2, ITGBL1, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A and VWA3B.
In some embodiments, the patient may have a connective tissue disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A1, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SHOX, SLC22A4 (includes EG:6583), TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have rheumatic disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TLR5, TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have arthritis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B, ZNF438.
In some embodiments, the patient may have atherosclerosis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, ASTN2 (includes EG:23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2, FOSB, FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM, ODZ2, OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have inflammatory bowel disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, APBA2, ASTN2 (includes EG:23245), CARD8, DIP2C, DNAH14, ERAP2, FBLN7, FREM2, GRM5, IL1B, LHX2, LNPEP, LTBR, MECOM, NOS3, ODZ2, OPCML, PAPPA, PDE1A, PPP1R1C, ROBO1, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SNRPN, SPON1, TGFB2, TLR5, VWA3B and ZNF438.
In some embodiments, the patient may have non-insulin-dependent diabetes mellitus and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG:23245), CARD8, CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, EPHA3, FAT1, FOXA2, GABRB2, IL1B, IQGAP2, ITGBL1, MBNL1, NOS3, NTM, ODZ2, PLSCR1, ROBO1, SLC22A4 (includes EG:6583), SLC2A3, SPON1, SRGAP1, TLR5, UNC84A and VWA3B.
In some embodiments, the patient may have rheumatoid arthritis and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, ADM, ASTN2 (includes EG:23245), BCL6, CARD8, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG:6583), TNFRSF21, TNPO1, TTC6 (includes EG:115669), VWA3B and ZNF438.
In some embodiments, the patient may have coronary artery disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, ASTN2 (includes EG:23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2, FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM, ODZ2, OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A and VWA3B.
In some embodiments, the patient may have Crohn's disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ACSL1, AK5, APBA2, ASTN2 (includes EG:23245), CARDS, DIP2C, DNAH14, ERAP2, FBLN7, FREM2, GRM5, LHX2, LNPEP, MECOM, ODZ2, OPCML, PAPPA, PDE1A, PPP1R1C, ROBO1, SFXN1, SLC22A4 (includes EG:6583), SLC26A8, SNRPN, SPON1, TGFB2, TLR5, VWA3B and ZNF438.
In some embodiments, the patient may have a neurodegenerative disorder and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ASTN2 (includes EG:23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM, NDST3, NOS3, OPCML, RFX2, SCN2A, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SPON1, TSHZ2 and ZNF608.
In some embodiments, the patient may have Alzheimer's disease and have increased or decreased expression relative to a control level of expression of a plurality of biomarkers selected from the group consisting of ASTN2 (includes EG:23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM, NDST3, NOS3, OPCML, RFX2, SLC22A4 (includes EG:6583), SLC2A3, SLC3A1, SPON1, TSHZ2 and ZNF608.

6. Methods of Detecting Biomarkers Associated with TIA

Gene expression may be measured using any method known in the art. One of skill in the art will appreciate that the means of measuring gene expression is not a critical aspect of the invention. The expression levels of the biomarkers can be detected at the transcriptional or translational (i.e., protein) level.
In some embodiments, the expression levels of the biomarkers are detected at the transcriptional level. A variety of methods of specific DNA and RNA measurement using nucleic acid hybridization techniques are known to those of skill in the art (see, Sambrook, supra and Ausubel, supra) and may be used to detect the expression of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. Some methods involve an electrophoretic separation (e.g., Southern blot for detecting DNA, Northern blot for detecting RNA, RNAse protection assays), but measurement of DNA and RNA can also be carried out in the absence of electrophoretic separation (e.g., by dot blot). Southern blot of genomic DNA (e.g., from a human) can be used for screening for restriction fragment length polymorphism (RFLP) to detect the presence of a genetic disorder affecting a polypeptide of the invention. All forms of RNA can be detected, including, e.g., message RNA (mRNA), microRNA (miRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA).
The selection of a nucleic acid hybridization format is not critical. A variety of nucleic acid hybridization formats are known to those skilled in the art. For example, common formats include sandwich assays and competition or displacement assays. Hybridization techniques are generally described in Hames and Higgins Nucleic Acid Hybridization, A Practical Approach, IRL Press (1985); Gall and Pardue, Proc. Natl. Acad. Sci. U.S.A., 63:378-383 (1969); and John et al. Nature, 223:582-587 (1969).
Detection of a hybridization complex may require the binding of a signal-generating complex to a duplex of target and probe polynucleotides or nucleic acids. Typically, such binding occurs through ligand and anti-ligand interactions as between a ligand-conjugated probe and an anti-ligand conjugated with a signal. The binding of the signal generation complex is also readily amenable to accelerations by exposure to ultrasonic energy.
The label may also allow indirect detection of the hybridization complex. For example, where the label is a hapten or antigen, the sample can be detected by using antibodies. In these systems, a signal is generated by attaching fluorescent or enzyme molecules to the antibodies or in some cases, by attachment to a radioactive label (see, e.g., Tijssen, “Practice and Theory of Enzyme Immunoassays,” Laboratory Techniques in Biochemistry and Molecular Biology, Burdon and van Knippenberg Eds., Elsevier (1985), pp. 9-20).
The probes are typically labeled either directly, as with isotopes, chromophores, lumiphores, chromogens, or indirectly, such as with biotin, to which a streptavidin complex may later bind. Thus, the detectable labels used in the assays of the present invention can be primary labels (where the label comprises an element that is detected directly or that produces a directly detectable element) or secondary labels (where the detected label binds to a primary label, e.g., as is common in immunological labeling). Typically, labeled signal nucleic acids are used to detect hybridization. Complementary nucleic acids or signal nucleic acids may be labeled by any one of several methods typically used to detect the presence of hybridized polynucleotides. The most common method of detection is the use of autoradiography with ³H, ¹²⁵I, ³⁵S, ¹⁴C, or ³²P-labeled probes or the like.
Other labels include, e.g., ligands that bind to labeled antibodies, fluorophores, chemiluminescent agents, enzymes, and antibodies which can serve as specific binding pair members for a labeled ligand. An introduction to labels, labeling procedures and detection of labels is found in Polak and Van Noorden Introduction to Immunocytochemistry, 2nd ed., Springer Verlag, NY (1997); and in Haugland Handbook of Fluorescent Probes and Research Chemicals, a combined handbook and catalogue Published by Molecular Probes, Inc. (1996).
In general, a detector which monitors a particular probe or probe combination is used to detect the detection reagent label. Typical detectors include spectrophotometers, phototubes and photodiodes, microscopes, scintillation counters, cameras, film and the like, as well as combinations thereof. Examples of suitable detectors are widely available from a variety of commercial sources known to persons of skill in the art. Commonly, an optical image of a substrate comprising bound labeling moieties is digitized for subsequent computer analysis.
Most typically, the amount of RNA is measured by quantifying the amount of label fixed to the solid support by binding of the detection reagent. Typically, the presence of a modulator during incubation will increase or decrease the amount of label fixed to the solid support relative to a control incubation which does not comprise the modulator, or as compared to a baseline established for a particular reaction type. Means of detecting and quantifying labels are well known to those of skill in the art.
In preferred embodiments, the target nucleic acid or the probe is immobilized on a solid support. Solid supports suitable for use in the assays of the invention are known to those of skill in the art. As used herein, a solid support is a matrix of material in a substantially fixed arrangement.
For example, in one embodiment of the invention, microarrays are used to detect the pattern of gene expression. Microarrays provide one method for the simultaneous measurement of the expression levels of large numbers of genes. Each array consists of a reproducible pattern of a plurality of nucleic acids (e.g., a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9) attached to a solid support. Labeled RNA or DNA is hybridized to complementary probes on the array and then detected by laser scanning. Hybridization intensities for each probe on the array are determined and converted to a quantitative read-out of relative gene expression levels in transient ischemic attacks.
In some embodiments, a sample is obtained from a subject, total mRNA is isolated from the sample and is converted to labeled cRNA and then hybridized to an array. Relative transcript levels are calculated by reference to appropriate controls present on the array and in the sample. See, Mahadevappa and Warrington, Nat. Biotechnol. 17, 1134-1136 (1999).
A variety of automated solid-phase assay techniques are also appropriate. For instance, very large scale immobilized polymer arrays (VLSIPS™), available from Affymetrix, Inc. (Santa Clara, Calif.) can be used to detect changes in expression levels of a plurality of genes involved in the same regulatory pathways simultaneously. See, Tijssen, supra., Fodor et al. (1991) Science, 251: 767-777; Sheldon et al. (1993) Clinical Chemistry 39(4): 718-719, and Kozal et al. (1996) Nature Medicine 2(7): 753-759. Integrated microfluidic systems and other point-of-care diagnostic devices available in the art also find use. See, e.g., Liu and Mathies, Trends Biotechnol. (2009) 27(10):572-81 and Tothill, Semin Cell Dev Biol (2009) 20(1):55-62. Microfluidics systems for use in detecting levels of expression of a plurality of nucleic acids are available, e.g., from NanoString Technologies, on the internet at nanostring.com.
Detection can be accomplished, for example, by using a labeled detection moiety that binds specifically to duplex nucleic acids (e.g., an antibody that is specific for RNA-DNA duplexes). One preferred example uses an antibody that recognizes DNA-RNA heteroduplexes in which the antibody is linked to an enzyme (typically by recombinant or covalent chemical bonding). The antibody is detected when the enzyme reacts with its substrate, producing a detectable product. Coutlee et al. (1989) Analytical Biochemistry 181:153-162; Bogulayski (1986) et al. J. Immunol. Methods 89:123-130; Prooijen-Knegt (1982) Exp. Cell Res. 141:397-407; Rudkin (1976) Nature 265:472-473, Stollar (1970) Proc. Nat'l Acad. Sci. USA 65:993-1000; Ballard (1982) Mol. Immunol. 19:793-799; Pisetsky and Caster (1982) Mol. Immunol. 19:645-650; Viscidi et al. (1988) J. Clin. Microbial. 41:199-209; and Kiney et al. (1989) J. Clin. Microbiol. 27:6-12 describe antibodies to RNA duplexes, including homo and heteroduplexes. Kits comprising antibodies specific for DNA:RNA hybrids are available, e.g., from Digene Diagnostics, Inc. (Beltsville, Md.).
In addition to available antibodies, one of skill in the art can easily make antibodies specific for nucleic acid duplexes using existing techniques, or modify those antibodies that are commercially or publicly available. In addition to the art referenced above, general methods for producing polyclonal and monoclonal antibodies are known to those of skill in the art (see, e.g., Paul (3rd ed.) Fundamental Immunology Raven Press, Ltd., NY (1993); Coligan, et al., Current Protocols in Immunology, Wiley Interscience (1991-2008); Harlow and Lane, Antibodies: A Laboratory Manual Cold Spring Harbor Press, NY (1988); Harlow and Lane, Using Antibodies, Cold Spring Harbor Press, NY (1999); Stites et al. (eds.) Basic and Clinical Immunology (4th ed.) Lange Medical Publications, Los Altos, Calif., and references cited therein; Goding Monoclonal Antibodies: Principles and Practice (2d ed.) Academic Press, New York, N.Y., (1986); and Kohler and Milstein Nature 256: 495-497 (1975)). Other suitable techniques for antibody preparation include selection of libraries of recombinant antibodies in phage or similar vectors (see, Huse et al. Science 246:1275-1281 (1989); and Ward et al. Nature 341:544-546 (1989)). Specific monoclonal and polyclonal antibodies and antisera will usually bind with a K_Dof at least about 0.1 μM, preferably at least about 0.01 μM or better, and most typically and preferably, 0.001 μM or better.
The nucleic acids used in this invention can be either positive or negative probes. Positive probes bind to their targets and the presence of duplex formation is evidence of the presence of the target. Negative probes fail to bind to the suspect target and the absence of duplex formation is evidence of the presence of the target. For example, the use of a wild type specific nucleic acid probe or PCR primers may serve as a negative probe in an assay sample where only the nucleotide sequence of interest is present.
The sensitivity of the hybridization assays may be enhanced through use of a nucleic acid amplification system that multiplies the target nucleic acid being detected. Examples of such systems include the polymerase chain reaction (PCR) system, in particular RT-PCR, multiplex PCR, quantitative PCR or real time PCR, and the ligase chain reaction (LCR) system. Other methods recently described in the art are the nucleic acid sequence based amplification (NASBA, Cangene, Mississauga, Ontario) and Q Beta Replicase systems. These systems can be used to directly identify mutants where the PCR or LCR primers are designed to be extended or ligated only when a selected sequence is present. Alternatively, the selected sequences can be generally amplified using, for example, nonspecific PCR primers and the amplified target region later probed for a specific sequence indicative of a mutation. High throughput multiplex nucleic acid sequencing or “deep sequencing” to detect captured expressed biomarker genes also finds use. High throughput sequencing techniques are known in the art (e.g., 454 Sequencing on the internet at 454.com).
An alternative means for determining the level of expression of the nucleic acids of the present invention is in situ hybridization. In situ hybridization assays are well known and are generally described in Angerer et al., Methods Enzymol. 152:649-660 (1987). In an in situ hybridization assay, cells, preferentially human cells, e.g., blood cells, are fixed to a solid support, typically a glass slide. If DNA is to be probed, the cells are denatured with heat or alkali. The cells are then contacted with a hybridization solution at a moderate temperature to permit annealing of specific probes that are labeled. The probes are preferably labeled with radioisotopes or fluorescent reporters.
In other embodiments, quantitative RT-PCR is used to detect the expression of a plurality of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. A general overview of the applicable technology can be found, for example, in A-Z of Quantitative PCR, Bustin, ed., 2004, International University Line; Quantitative PCR Protocols, Kochanowski and Reischl, eds., 1999, Humana Press; Clinical Applications of PCR, Lo, ed., 2006, Humana Press; PCR Protocols: A Guide to Methods and Applications (Innis et al. eds. (1990)) and PCR Technology: Principles and Applications for DNA Amplification (Erlich, ed. (1992)). In addition, amplification technology is described in U.S. Pat. Nos. 4,683,195 and 4,683,202. Methods for multiplex PCR, known in the art, are applicable to the present invention.
Accordingly, in one embodiment of the invention provides a reaction mixture comprising a plurality of polynucleotides which specifically hybridize (e.g., primers) to a plurality of nucleic acid sequences of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. In some embodiments, the reaction mixture is a PCR mixture, for example, a multiplex PCR mixture.
This invention relies on routine techniques in the field of recombinant genetics. Generally, the nomenclature and the laboratory procedures in recombinant DNA technology described below are those well known and commonly employed in the art. Standard techniques are used for cloning, DNA and RNA isolation, amplification and purification. Generally enzymatic reactions involving DNA ligase, DNA polymerase, restriction endonucleases and the like are performed according to the manufacturer's specifications. Basic texts disclosing the general methods of use in this invention include Sambrook et al., Molecular Cloning, A Laboratory Manual (3rd ed. 2001); Kriegler, Gene Transfer and Expression: A Laboratory Manual (1990); and Current Protocols in Molecular Biology (Ausubel et al., eds., 1994-2008, Wiley Interscience)).
For nucleic acids, sizes are given in either kilobases (kb) or base pairs (bp). These are estimates derived from agarose or acrylamide gel electrophoresis, from sequenced nucleic acids, or from published DNA sequences. For proteins, sizes are given in kilodaltons (kDa) or amino acid residue numbers. Proteins sizes are estimated from gel electrophoresis, from sequenced proteins, from derived amino acid sequences, or from published protein sequences.
Oligonucleotides that are not commercially available can be chemically synthesized according to the solid phase phosphoramidite triester method first described by Beaucage & Caruthers, Tetrahedron Letts. 22:1859-1862 (1981), using an automated synthesizer, as described in Van Devanter et. al., Nucleic Acids Res. 12:6159-6168 (1984). Purification of oligonucleotides is by either native acrylamide gel electrophoresis or by anion-exchange HPLC as described in Pearson & Reanier, J. Chrom. 255:137-149 (1983).
In some embodiments, the expression level of the biomarkers described herein are detected at the translational or protein level. Detection of proteins is well known in the art, and methods for protein detection known in the art find use. Exemplary assays for determining the expression levels of a plurality of proteins include, e.g., ELISA, flow cytometry, mass spectrometry (e.g., MALDI or SELDI), surface plasmon resonance (e.g., BiaCore), microfluidics and other biosensor technologies. See, e.g., Tothill, Semin Cell Dev Biol (2009) 20(1):55-62.

7. TIA Reference Profiles

The invention also provides ischemia reference profiles. The TIA reference profiles comprise information correlating the expression levels of a plurality of TIA-associated genes (i.e., a plurality of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9) to the occurrence or risk of TIA. The profiles can conveniently be used to diagnose, monitor and prognose ischemia.
The reference profiles can be entered into a database, e.g., a relational database comprising data fitted into predefined categories. Each table, or relation, contains one or more data categories in columns. Each row contains a unique instance of data for the categories defined by the columns. For example, a typical database for the invention would include a table that describes a sample with columns for age, gender, reproductive status, expression profile and so forth. Another table would describe a disease: symptoms, level, sample identification, expression profile and so forth. In one embodiment, the invention matches the experimental sample to a database of reference samples. The database is assembled with a plurality of different samples to be used as reference samples. An individual reference sample in one embodiment will be obtained from a patient during a visit to a medical professional. Information about the physiological, disease and/or pharmacological status of the sample will also be obtained through any method available. This may include, but is not limited to, expression profile analysis, clinical analysis, medical history and/or patient interview. For example, the patient could be interviewed to determine age, sex, ethnic origin, symptoms or past diagnosis of disease, and the identity of any therapies the patient is currently undergoing. A plurality of these reference samples will be taken. A single individual may contribute a single reference sample or more than one sample over time. One skilled in the art will recognize that confidence levels in predictions based on comparison to a database increase as the number of reference samples in the database increases.
The database is organized into groups of reference samples. Each reference sample contains information about physiological, pharmacological and/or disease status. In one aspect the database is a relational database with data organized in three data tables, one where the samples are grouped primarily by physiological status, one where the samples are grouped primarily by disease status and one where the samples are grouped primarily by pharmacological status. Within each table the samples can be further grouped according to the two remaining categories. For example the physiological status table could be further categorized according to disease and pharmacological status.
As will be appreciated by one of skill in the art, the present invention may be embodied as a method, data processing system or program products. Accordingly, the present invention may take the form of data analysis systems, methods, analysis software, etc. Software written according to the present invention is to be stored in some form of computer readable medium, such as memory, hard-drive, DVD ROM or CD ROM, or transmitted over a network, and executed by a processor. The present invention also provides a computer system for analyzing physiological states, levels of disease states and/or therapeutic efficacy. The computer system comprises a processor, and memory coupled to said processor which encodes one or more programs. The programs encoded in memory cause the processor to perform the steps of the above methods wherein the expression profiles and information about physiological, pharmacological and disease states are received by the computer system as input. Computer systems may be used to execute the software of an embodiment of the invention (see, e.g., U.S. Pat. No. 5,733,729).

8. Providing Appropriate Treatment and Prevention Regimes to Patient

In some embodiments, the methods further comprise the step of prescribing and providing appropriate treatment and/or prevention regimes to a patient diagnosed as having TIA or at risk of the occurrence of TIA or stroke. For example, medications and life-style adjustments (e.g., diet, exercise, stress) to minimize risk factors can be recommended, including reducing blood pressure and cholesterol levels, and controlling diabetes.
In additions, several medications to decrease the likelihood of a stroke after a transient ischemic attack. The medication selected will depend on the location, cause, severity and type of TIA, if TIA has occurred.
In some embodiments, the patient may be prescribed a regime of an anti-platelet drug. The most frequently used anti-platelet medication is aspirin. An alternative to aspirin is the anti-platelet drug clopidogrel (Plavix). Some studies indicate that aspirin is most effective in combination with another anti-platelet drug. In some embodiments, the patient is prescribed a combination of low-dose aspirin and the anti-platelet drug dipyridamole (Aggrenox), to reduce blood clotting. Ticlopidine (Ticlid) is another anti-platelet medication that finds use to prevent or reduce the risk of stroke in patients who have experienced TIA.
In some embodiments, the patient may be prescribed a regime of an anticoagulant. Exemplary anticoagulants include aspirin, heparin, warfarin, and dabigatran.
Patients having a moderately or severely narrowed neck (carotid) artery, may require or benefit from carotid endarterectomy. This preventive surgery clears carotid arteries of fatty deposits (atherosclerotic plaques) before another TIA or stroke can occur. In some embodiments, the patient may require or benefit from carotid angioplasty, or stenting. Carotid angioplasty involves using a balloon-like device to open a clogged artery and placing a small wire tube (stent) into the artery to keep it open.

9. Solid Supports and Kits

The invention further provides a solid supports comprising a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9, and optionally Table 3. For example, the solid support can be a microarray attached to a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Table 1, and optionally Table 3. In various embodiments, the solid support can be a microarray attached to a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Tables 5A, 5B, 5C, and 5D, and optionally Table 3. In various embodiments, the solid support can be a microarray attached to a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Table 7, and optionally Table 3. In various, the solid support can be a microarray attached to a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Table 8, and optionally Table 3. In various, the solid support can be a microarray attached to a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes set forth in Table 9, and optionally Table 3.
In various embodiments, the solid supports are configured to exclude genes not associated with or useful to the diagnosis, prediction or confirmation of a stroke or the causes of stroke. For example, genes which are overexpressed or underexpressed less than 1.5-fold in subjects having or suspected of having TIA, in comparison to a control level of expression can be excluded from the present solid supports. In some embodiments, genes that are overexpressed or underexpressed less than 1.2-fold in subjects with ischemic stroke, including cardioembolic stroke, atherothrombotic stroke, and stroke subsequent to atrial fibrillation, in comparison to a control level of expression can be excluded from the present solid supports. The solid support can comprise a plurality of nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes useful for the diagnosis of ischemic stroke, cardioembolic stroke, carotid stenosis, and/or atrial fibrillation, as described herein. As appropriate, nucleic acid probes that hybridize to a plurality (e.g., two or more, or all) of the genes useful for the diagnosis of ischemic stroke, cardioembolic stroke, carotid stenosis, and/or atrial fibrillation can be arranged in a predetermined array on the solid support. In various embodiments, nucleic acids not specifically identified and/or not relating to the diagnosis of and/or not associated with the diagnosis of TIA are not attached to the solid support. In various embodiments, nucleic acids not specifically identified and/or not relating to the diagnosis of and/or not associated with the diagnosis of ischemic stroke, cardioembolic stroke, carotid stenosis, and/or atrial fibrillation are not attached to the solid support. The solid support may be a component in a kit.
The invention also provides kits for diagnosing TIA or a predisposition for developing TIA. For example, the invention provides kits that include one or more reaction vessels that have aliquots of some or all of the reaction components of the invention in them. Aliquots can be in liquid or dried form. Reaction vessels can include sample processing cartridges or other vessels that allow for the containment, processing and/or amplification of samples in the same vessel. The kits can comprise a plurality of nucleic acid probes that hybridize to a plurality the genes set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. The probes may be immobilized on a microarray as described herein.
In addition, the kit can comprise appropriate buffers, salts and other reagents to facilitate amplification and/or detection reactions (e.g., primers, labels) for determining the expression levels of a plurality of the biomarkers set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. The kits can also include written instructions for the use of the kit.
In one embodiment, the kits comprise a plurality of antibodies that bind to a plurality of the biomarkers set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and/or 9. The antibodies may or may not be immobilized on a solid support, e.g., an ELISA plate.

EXAMPLES

The following examples are offered to illustrate, but not to limit the claimed invention.

Example 1

Materials and Methods

Subjects

TIA and control patients were recruited from the University of California Davis Medical Center, University of California San Francisco Medical Center and Wake Forest University Health Sciences. Institutional Review Boards at each institution approved the study, and written informed consent was obtained from all patients.
A total of 27 control patients were compared to 24 TIA patients studied within 3 to 69 hours (average=29.2 hours) of symptoms onset. The diagnosis of TIA was made by two independent board certified neurologists with access to all clinical data. TIA was defined as an acute loss of focal cerebral or ocular function lasting <12 hours with a presumed ischemic etiology. To be recruited into the study TIA patients were required to have an ABCD²score≧4 to further support the diagnosis of TIA. This ensured that TIA patients at higher risk for recurrent vascular events were studied (4, 19). The controls were recruited from the spouses or family members of TIA patients or people from the community. They were subjects free of vascular events such as TIA, ischemic stroke, myocardial infarction, peripheral vascular disease, or venous thromboembolism. Control subjects with hypertension and/or diabetes were also excluded in order to reduce the possibility of controls having silent TIA or other vascular events. Hypertension and diabetes both increase the probability of TIA, as shown by the ABCD²score (4, 20).

RNA Isolation

A venous blood sample was collected into PAXgene vacutainers (PreAnalytiX, Hilden, Germany). Total RNA was isolated according to the manufacturer's protocol.

Microarray Hybridization

Biotin-labeled cDNA was synthesized from 50 ng of total RNA using the Ovation Whole Blood Solution (Nugen) kit according to protocol. Each RNA sample was processed on Affymetrix Human Genome HG-U133-Plus-2.0 microarrays as previously described (18).

Statistical Analysis

Microarray probeset-level data were log transformed and normalized using Robust Multichip Average (RMA). Analysis of Covariance (ANCOVA) was conducted in Partek Genomics Suite 6.5 (Partek Inc., St. Louis, Mich., USA) to identify genes/probes significantly different between TIA and control subjects with adjustment for microarray batch effect and age. Genes/probes were considered significant with a p-value≦0.05 after Benjamini-Hochberg multiple-comparison correction, and an absolute fold change>1.5. To exclude genes associated with hypertension, a second comparison was performed for 33 controls with hypertension to controls without hypertension. The Identified “hypertension” genes that overlapped with the TIA gene lists were excluded from further analysis.
All data are presented as mean±SE. Differences in demographic data between groups were analyzed using Chi-square test or t-test as appropriate. Prediction analysis was performed using 10-fold leave-one-out cross-validation in Prediction Analysis of Microarrays (PAM). Functional and pathway analyses were performed using Ingenuity Pathways Analysis (IPA).

Results

Subjects

The demographic information for TIA and control subjects showed that age was significantly different between TIA and controls (Table 4). Thus, age was adjusted for in the ANCOVA model.

TABLE 4

Demographic summary of Transient Ischemic
Attack (TIA) patients and control subjects

Controls	TIA
(n = 27)	(n = 24)	p value

Age (yrs ± SE)	55.7 ± 0.8	70.2 ± 2.5	<0.001
Gender Female: n (%)	19 (70.4)	14 (58.3)	0.39
Race
Caucasian: n (%)	18 (66.6)	16 (66.6)	1.00
Non-Caucasian: n (%)	9 (33.3)	8 (33.3)	1.00

TIA Genomic Profiles

A total of 460 genes were differentially expressed between TIA patients and controls (FDR≦0.05; fold change≧1.5) (Tables 5A-D). 135 genes were down-regulated (Table 2 and Table 5A) and 325 were up-regulated (Table 1 and Table 5B) in TIA compared to controls. A Hierarchical cluster analysis of the 460 genes showed that they separated TIAs from controls (FIG. 1) except that two TIA patients (ID numbers: 57 and 90) clustered in the control group, and three control patients (ID numbers: 42, 68 and 74) clustered in the TIA group (FIG. 1). The hierarchical cluster analysis also suggested the presence of two distinct TIA groups. Most of the up-regulated genes in the TIAL group separated it from the TIA2 group and from controls (FIG. 1).

Prediction Analysis

Cross-correlation performed with PAM using the 34 (Table 5C) out of 460 TIA associated genes distinguished TIA patients from controls with 87.5% sensitivity (21 out of 24 TIAs correctly classified) and 96.3% specificity (26 out of 27 controls correctly classified) (FIG. 2).

TIA Specific Up-regulated Genes

The 325 up-regulated genes that distinguished TIA1 from TIA2 patients were input into PAM to derive the minimum number (n=26) of genes that differentiated the two groups. The 26 genes (Table 5D) distinguished TIA1 from TIA2 patients with 100% sensitivity and specificity (FIG. 3). No clinical factors were identified that were significantly different between TIA1 and TIA2 including age, time after TIA, hypertension, diabetes, ABCD²score (Table 6) and medications. Notably, Metalloproteinase 16 and Metalloproteinase 26 were up-regulated in the TIA1 group but not in the TIA2 group (FIG. 4).

TABLE 6

Demographic Summary of TIA subgroups

	TIA1 (n = 12)	TIA2 (n = 12)	P value

Age (yrs ± SE)	64.8 ± 3.7	63.7 ± 8.8	0.91
Gender Female (%)	5 (42)	5 (42)	1.00
Race
Caucasian n (%)	7 (58)	9 (75)	0.18
Non-Caucasian n (%)	5 (42)	3 (25)	0.18
Vascular risk factor
Hypertension n (%)	10 (83)	10 (83)	1.00
Diabetes n (%)	4 (33)	4 (33)	1.00
Hyperlipidemia n (%)	6 (50)	7 (58)	0.56
Smoke n (%)	6 (50)	4 (33)	0.22
Hours since TIA (±SE)	28.7 ± 4.4	29.7 ± 4.3	0.87
History of stroke n (%)	3 (25)	4 (33)	0.54
CVD n (%)	3 (25)	4 (33)	0.54
AF n (%)	1 (8)	2 (16)	0.43
LVD n (%)	1 (8)	2 (16)	0.43
ABCD²score (±SE)	5.42 ± 0.29	5.25 ± 0.28	0.68

CVD: Cardiovascular Disorder;
AF: Atrial Fibrillation;
LVD: Large Vessel Disease.
There was no any significant difference among two groups analyzed using t-test or Chi-square test.
The factors contributed to the differences in RNA expression between TIA1 and TIA2 remained unclear.

Function Analysis of TIA Specific Genes

Functional analysis of the TIA specific genes (460 genes derived from TIA vs control) using IPA demonstrated that they were significantly associated with immune functions. Amongst the TIA specific genes, a number have been associated with autoimmune disease, diabetes, arthritis, rheumatoid arthritis, atherosclerosis, coronary artery disease and Crohn's disease (Table 7). The significantly regulated genes for the TIAL group compared to the TIA2 group (FDR≦0.05; fold change≧1.5) are shown in Table 8 along with the most significant pathways (Table 9; see discussion below).

TABLE 7

TIA specific gene-functions

Category	Function	p-value	Molecules

Genetic	genetic	2.29E−03	ACSL1, ADAM30, ADAMDEC1, ADH1B, AK5, ALPL, ALS2CR11, ANXA3, APBA2, ASTN2 (includes
Disorder	disorder		EG: 23245), BCL6, BMPR1B, CACNA1I, CARD8, CARD16, CASP5, CAV1, CCND3, CCRL1, CHIT1,
			CLTC, CNTLN, CNTN4, COL1A1, COL1A2, DIP2C, DMRT1, DNAH14, EDAR, ELAVL2, EPHA3,
			EPHX2, ERAP2, FAM124A, FAM13A, FAM149A, FAT1, FBLN7, FOLH1, FOXA2, FOXC1, FREM2,
			GABRB2, GIGYF2, GNAO1, GRM5, GSTM1, GYPA, HESX1, HOXC6, IGFBP5, IL1B, IQGAP2,
			ITGBL1, LAMB4, LHX2, LIFR, LNPEP, LRP2, LTBR, MAN1C1, MBNL1, MCF2L, MECOM, MLL,
			NBPF10, NDST3, NELL2, NOS3, NTM, ODZ2, OLFM2, OPCML, OSM, PAPPA, PDE1A, PLSCR1,
			PPP1R1C, RFX2, ROBO1, RORB, S100A12, SCN2A, SFXN1, SHOX, SIX3, SLC22A4 (includes
			EG: 6583), SLC26A8, SLC2A3, SLC3A1, SMURF2, SNRPN, SOX9, SPOCK3, SPON1, SRGAP1,
			TFAP2B, TGFB2, TLR5, TRPM1, TSHZ2, TTC6 (includes EG: 115669), TWIST1, UNC5B, UNC84A,
			VWA3B, ZNF438, ZNF608
Neurological	neurological	1.99E−02	ACSL1, ADH1B, AK5, ANXA3, APBA2, ASTN2 (includes EG: 23245), BCL6, BMPR1B, CASP5, CAV1,
Disease	disorder		CNTN4, DIP2C, ELAVL2, EPHX2, ERAP2, FAM124A, FAM13A, FAM149A, FAT1, FOLH1, FOXC1,
			GABRB2, GIGYF2, GNAO1, GRM5, GSTM1, HESX1, HOXC6, IGFBP5, IL1B, IQGAP2, ITGBL1,
			LAMB4, LIFR, LTBR, MECOM, NBPF10, NDST3, NELL2, NOS3, NTM, ODZ2, OLFM2, OPCML,
			PDE1A, RFX2, ROBO1, S100A12, SCN2A, SLC22A4 (includes EG: 6583), SLC2A3, SLC3A1, SOX9,
			SPOCK3, SPON1, TGFB2, TLR5, TNFRSF21, TRPM1, TSHZ2, TTC6 (includes EG: 115669), UNC5B,
			UNC84A, ZNF608
Inflam-	inflam-	8.17E−06	ACSL1, ADM, AK5, ANXA3, APBA2, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CAV1,
matory	matory		CCND3, CCRL1, CLTC, CNTN4, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, ERAP2, FAM124A,
Disease	disorder		FBLN7, FOSB, FREM2, GABRB2, GRM5, IL1B, KCNJ15, LAMB4, LHX2, LNPEP, LRP2, LTBR, LUM,
			MAPK14, MECOM, MYBPC1, NOS3, ODZ2, OPCML, OSM, PAPPA, PDE1A, PPP1R1C, ROBO1,
			RUNDC3B, S100A12, SCN2A, SFXN1, SLC22A4 (includes EG: 6583), SLC26A8, SMURF2, SNRPN,
			SPON1, TGFB2, TLR5, TNFRSF21, TNPO1, TTC6 (includes EG: 115669), TWIST1, UNC5B, VWA3B,
			ZNF438
Skeletal and	skeletal and	2.32E−03	ACSL1, ADM, AK5, ASTN2 (includes EG: 23245), BCL6, BMPR1B, CARD8, CASP5, CCND3, CLTC,
Muscular	muscular		CNTN4, COL1A1, COL1A2, DIP2C, DNAH14, EDAR, ELAVL2, EPHA3, EPHX2, FAM124A, FOSB,
Disorders	disorder		GABRB2, GIGYF2, GNAO1, HOXC6, IL1B, KCNJ15, LAMB4, LIFR, LTBR, LUM, MAPK14, MYBPC1,
			NOS3, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SCN2A, SHOX, SLC22A4
			(includes EG: 6583), SOX9, SPOCK3, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6 (includes
			EG: 115669), TWIST1, UNC5B, VWA3B, ZNF438
Cardio-	cardio-	3.05E−05	ACSL1, ADM, AK5, ALPL, ASTN2 (includes EG: 23245), BCL6, BMPR1B, C18ORF54, CACNA1I,
vascular	vascular		CARD16, CAV1, CNTN4, DMRT1, DNAH14, EDAR, EPHX2, ERAP2, FAM13A, FOLH1, FOSB,
Disease	disorder		FREM2, GABRB2, GRM5, GSTM1, IL1B, IQGAP2, LIFR, LTBR, MAN1C1, MAPK14, MBNL1, MCF2L,
			MECOM, MYBPC1, NOS3, NTM, ODZ2, OLFM2, OPCML, PAPPA, PDE1A, ROBO1, RORB,
			S100A12, SMURF2, SNRPN, SOX9, SPOCK3, SPON1, TFPI, TRPM1, UNC84A, VWA3B
Immuno-	immuno-	2.11E−04	ACSL1, ADM, AK5, ANXA3, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CCND3, CCRL1,
logical	logical		CLTC, CNTN4, COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FAT1, FOSB,
Disease	disorder		GABRB2, GOLGA6L2, GSTM1, GUSBL2, IL1B, IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14,
			MYBPC1, NELL2, NOS3, NTM, ODZ2, OPCML, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B,
			S100A12, SLC22A4 (includes EG: 6583), SNRPN, SPON1, TLR5, TNFRSF21, TNPO1, TSHZ2, TTC6
			(includes EG: 115669), VWA3B, ZNF438
Metabolic	metabolic	1.03E−02	ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5,
Disease	disorder		CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, EPHX2, FAT1, FOXA2,
			GABRB2, GUSBL2, IGFBP5, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3,
			NTM, ODZ2, OPCML, PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG: 6583), SLC2A3, SLC3A1,
			SMURF2, SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A, VWA3B
Endocrine	endocrine	3.00E−03	ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5,
System	system		CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2,
Disorders	disorder		GUSBL2, IL1B, IQGAP2, ITGBL1, LRP2, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2,
			OPCML, PAPPA, PLSCR1, ROBO1, SHOX, SLC22A4 (includes EG: 6583), SLC2A3, SMURF2,
			SNRPN, SPON1, SRGAP1, TLR5, TSHZ2, UNC84A, VWA3B
Immuno-	autoimmune	3.60E−04	ACSL1, ADM, AK5, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4,
logical	disease		COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, GUSBL2, IL1B,
Disease			IQGAP2, KCNJ15, LAMB4, LTBR, MAPK14, MYBPC1, NELL2, ODZ2, OPCML, OSM, PAPPA,
			PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG: 6583), SNRPN, SPON1, TLR5,
			TNFRSF21, TNPO1, TSHZ2, TTC6 (includes EG: 115669), VWA3B, ZNF438
Endocrine	diabetes	2.09E−03	ACSL1, ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5,
System			CCRL1, CNTLN, CNTN4, COL1A2, DIP2C, DMRT1, DNAH14, EPHA3, FAT1, FOXA2, GABRB2,
Disorders			GUSBL2, IL1B, IQGAP2, ITGBL1, LTBR, MAPK14, MBNL1, NELL2, NOS3, NTM, ODZ2, OPCML,
			PAPPA, PLSCR1, ROBO1, SLC22A4 (includes EG: 6583), SLC2A3, SMURF2, SNRPN, SPON1,
			SRGAP1, TLR5, TSHZ2, UNC84A, VWA3B
Connective	connective	2.72E−04	ACSL1, ADM, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, COL1A1,
Tissue	tissue		COL1A2, DIP2C, DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15,
Disorders	disorder		LAMB4, LTBR, LUM, MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SHOX,
			SLC22A4 (includes EG: 6583), TLR5, TNFRSF21, TNPO1, TTC6 (includes EG: 115669), VWA3B,
			ZNF438
Cell Death	apoptosis	1.65E−02	ADM, AIM2, BCL6, BMPR1B, CARD8, CASP5, CAV1, CCND3, EDAR, FOSB, FOXA2, FUS, GALNT5,
			GNAO1, GRM5, HOXC6, IGFBP5, IL1B, IQGAP2, LTBR, MAPK14, MCF2L, MECOM, MLL, NOS3,
			OSM, PIWIL1, PLSCR1, POU2AF1, SCN2A, SHOX, SLC2A3, SOX9, TFAP2B, TGFB2, TNFRSF21,
			TWIST1, UNC5B
Gene	transcription	4.26E−04	BCL6, BMPR1B, CAV1, CCND3, EHF, ELAVL2, FOSB, FOXA2, FOXC1, FUS, GRM5, HELLS,
Expression			HOXC6, IL1B, LTBR, MAPK14, MECOM, MED6, MEG3 (includes EG: 55384), MLL, NR2F2, OSM,
			OVOL2, POU2AF1, RBM14, RORB, SHOX, SHOX2, SIX3, SLC3A1, SMURF2, SOX8, SOX9, SOX11,
			TFAP2B, TGFB2, TWIST1, ZNF462
Inflam-	rheumatic	8.49E−04	ACSL1, ADM, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C,
matory	disease		DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM,
Disease			MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG: 6583),
			TLR5, TNFRSF21, TNPO1, TTC6 (includes EG: 115669), VWA3B, ZNF438
Inflam-	arthritis	7.29E−04	ACSL1, ADM, ASTN2 (includes EG: 23245), BCL6, CARD8, CASP5, CCND3, CLTC, CNTN4, DIP2C,
matory			DNAH14, EDAR, EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, LTBR, LUM,
Disease			MAPK14, ODZ2, OSM, PAPPA, PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG: 6583),
			TNFRSF21, TNPO1, TTC6 (includes EG: 115669), VWA3B, ZNF438
Cellular	proliferation	5.91E−03	ADM, AIM2, BCL6, BMPR1B, CAV1, CCND3, CLTC, COL1A1, DLX6, DPPA4, FOSB, FOXA2, FUS,
Growth			GRM5, GSTM1, HOXC6, IGFBP5, IL1B, LIFR, MAPK14, MECOM, MEG3 (includes EG: 55384), MLL,
and-			NOS3, OSM, PAPPA, PIWIL1, PLSCR1, SHOX2, SOX9, TFPI, TGFB2, TLR5, TNFRSF21
Prolifer-
ation
Cardio-	athero-	1.22E−04	ACSL1, AK5, ASTN2 (includes EG: 23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2,
vascular	sclerosis		FOSB, FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM,
Disease			ODZ2, OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A, VWA3B
Inflam-	inflam	5.07E−05	ACSL1, AK5, APBA2, ASTN2 (includes EG: 23245), CARD8, DIP2C, DNAH14, ERAP2, FBLN7,
matory	matory		FREM2, GRM5, IL1B, LHX2, LNPEP, LTBR, MECOM, NOS3, ODZ2, OPCML, PAPPA, PDE1A,
Disease	bowel		PPP1R1C, ROBO1, SFXN1, SLC22A4 (includes EG: 6583), SLC26A8, SNRPN, SPON1, TGFB2,
	disease		TLR5, VWA3B, ZNF438
Endocrine	non-insulin-	4.48E−04	ADAM30, AK5, ALPL, ALS2CR11, ASTN2 (includes EG: 23245), CARD8, CCRL1, CNTLN, CNTN4,
System	dependent		COL1A2, DIP2C, DMRT1, EPHA3, FAT1, FOXA2, GABRB2, IL1B, IQGAP2, ITGBL1, MBNL1, NOS3,
Disorders	diabetes		NTM, ODZ2, PLSCR1, ROBO1, SLC22A4 (includes EG: 6583), SLC2A3, SPON1, SRGAP1, TLR5,
	mellitus		UNC84A, VWA3B
Inflam-	rheumatoid	1.54E−03	ACSL1, ADM, ASTN2 (includes EG: 23245), BCL6, CARD8, CLTC, CNTN4, DIP2C, DNAH14, EDAR,
matory	arthritis		EPHA3, EPHX2, FAM124A, FOSB, GABRB2, IL1B, KCNJ15, LAMB4, MAPK14, ODZ2, OSM, PAPPA,
Disease			PDE1A, ROBO1, RUNDC3B, S100A12, SLC22A4 (includes EG: 6583), TNFRSF21, TNPO1, TTC6
			(includes EG: 115669), VWA3B, ZNF438
Cardio-	coronary	6.94E−05	ACSL1, AK5, ASTN2 (includes EG: 23245), BMPR1B, CARD16, CNTN4, DMRT1, DNAH14, ERAP2,
vascular	artery		FREM2, GRM5, IL1B, IQGAP2, LIFR, MAN1C1, MBNL1, MCF2L, MECOM, NOS3, NTM, ODZ2,
Disease	disease		OLFM2, PDE1A, ROBO1, RORB, SNRPN, SPOCK3, SPON1, TRPM1, UNC84A, VWA3B
Cell Death	cell death	7.84E−03	ADM, AIM2, BCL6, CARD8, CAV1, CCND3, DPPA4, FOSB, FOXA2, FUS, GALNT5, GNAO1, GSTM1,
			HOXC6, IGFBP5, IL1B, LTBR, MAPK14, MLL, NOS3, PIWIL1, PLSCR1, SHOX, SOX9, TFAP2B,
			TGFB2, TNFRSF21, TWIST1, UNC5B
Inflam-	Crohn's	2.08E−04	ACSL1, AK5, APBA2, ASTN2 (includes EG: 23245), CARD8, DIP2C, DNAH14, ERAP2, FBLN7,
matory	disease		FREM2, GRM5, LHX2, LNPEP, MECOM, ODZ2, OPCML, PAPPA, PDE1A, PPP1R1C, ROBO1,
Disease			SFXN1, SLC22A4 (includes EG: 6583), SLC26A8, SNRPN, SPON1, TGFB2, TLR5, VWA3B, ZNF438
Neurological	neuro-	1.57E−62	ASTN2 (includes EG: 23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM,
Disease	degenerative		NDST3, NOS3, OPCML, RFX2, SCN2A, SLC22A4 (includes EG: 6583), SLC2A3, SLC3A1, SPON1,
	disorder		TSHZ2, ZNF608
Neurological	Alzheimer's	1.72E−02	ASTN2 (includes EG: 23245), CASP5, CNTN4, FAM124A, FOLH1, GABRB2, GRM5, IL1B, MECOM,
Disease	disease		NDST3, NOS3, OPCML, RFX2, SLC22A4 (includes EG: 6583), SLC2A3, SLC3A1, SPON1, TSHZ2,
			ZNF608

Discussion

TIA is a harbinger of stroke and other vascular events. The present biomarker panels find use for intervention in TIA to prevent future vascular events. Prior to the present invention, there was limited knowledge regarding human TIA biology, and the development of specific TIA therapies has been limited. The present biomarker panels provide information to better understand the immune response in blood that occurs in patients with TIA. By examining the whole genome, unique TIA gene expression profiles showing two TIA subtypes were identified. These findings provide unique insight into TIA pathophysiology, and are consistent with the conclusion that there are specific immune responses that occur following transient focal cerebral ischemia in humans. They also suggest diagnostic tests to confirm a TIA diagnosis can be developed.

Systemic Inflammation and TIA

TIA patients appear to have unique patterns of inflammation associated with their vascular events. Indeed, compared to controls, TIA patients tend to have increased leukocyte activation and a systemic inflammatory response (8-9). Transient ischemic attacks have also been associated with a number of systemic inflammatory markers such as CRP (7), and inflammatory conditions such as inflammatory bowel disease (21-24). Alterations in immune function in TIAs are further implicated by an association between TIA and systemic infection, as well as TIA and periodontal disease (25-29). In this study, 63 genes involved in inflammation were differentially expressed in TIA compared to controls (Table 7). These genes show patterns of inflammation similar to that of inflammatory bowel disease (32 genes), rheumatoid arthritis (32 genes), and Crohn's disease (29 genes), suggesting that different, but related patterns of inflammation are associated with TIA. If the expression of these genes changed in a time-dependent manner after TIA onset, the inflammation could be a consequence of TIA. Otherwise, there might be some pre-existing inflammation that did not change with time that might promote the development of TIA. Therefore, a time-dependent analysis on the gene expression in the acute phase (blood draw within 24 h of TIA onset; n=11) and the sub acute phase (blood draw between 24 h to 72 h of TIA onset; n=13) of TIA was performed. The results showed that the large majority of the genes expressed in the acute phase were similar to those expressed in the sub acute phase (>90% similar). Thus, there may be a chronic inflammatory state prior to TIA and this could contribute to causing TIAs.

Anti-Oxidant Capacity

GSTM1 and GSTM2 encode cytosolic glutathione S-transferases (GSTs) that belong to the mu class. GST enzymes function in the detoxification of electrophilic compounds, such products of oxidative stress by conjugation with glutathione (30). GSTM1 and GSTM2 were both down-regulated in TIA patients, suggesting a decreased anti-oxidant capacity may exist in patients with TIAs. The resultant enhanced oxidative stress may in turn promote ischemic vascular disease such as TIA. This result is consistent with our previous animal study that showed a specific GST family member (GSTT1) regulated following 10 minutes of brief focal ischemia simulating human TIAs (5).

Extracellular Matrix Remodeling

Our data suggest the presence of two subgroups of TIA patients. No measured clinical factor was significantly different between each group. The notion of subtypes of TIA is not new. For example, TIA subtypes exist based on MRI DWI status, ABCD²score, or the presence of large vessel disease or atrial fibrillation. In our study, two molecular subtypes of TIA were evident based on gene expression profiles. Functional analysis of these two groups suggested over representation of genes involved in extracellular matrix remodeling in TIA1 compared to TIA2 including: MMP16, MMP19, MMP26, COL1A1, COL1A2, COL3A1, COL10A1, COL11A1, COL25A1, COL27A1, FGFs and EGFR. TIA1 patients may be more prone to extracellular matrix breakdown at the blood brain barrier and/or in atherosclerotic plaque.

Limitations of the Study

The sample size is small. A control group at very low risk of TIA and other vascular events was chosen so that the controls would be very unlikely to have silent ischemic events that would complicate comparison to TIA. By doing so, differences due to vascular risk factors are inevitably introduced. These factors were adjusted for by including age in the ANCOVA model, and excluding genes associated with hypertension and diabetes. The advantage of comparing TIA to the controls in this study, therefore, is that the gene expression differences between TIA and controls were maximized, and allowed for the search for TIA subgroups. However, future studies will need to compare TIA patients to other controls to identify “TIA specific gene markers”. These controls should include patients with similar vascular risk factors and “TIA mimic” patients with migraine or seizures.
Group heterogeneity is another limitation in the study of TIA. Though stringent criteria were used to ensure subjects with TIA were indeed true transient ischemic events, it is possible that a few TIA patients were in fact TIA mimics. Similarly, though a comparison group at low risk for having silent ischemic vascular events was used, it is possible some patients in the control group had silent vascular events.
This is a discovery type study and thus there is no previous study to compare to. Though FDR correction was applied, the only way to account for multiple comparisons is to perform a future replication study. PCR verification was not performed since most changes on Affymetrix arrays have correlated extremely well with PCR in previous studies. In addition, PCR would only be needed once this study has been replicated and the PCR confirmed genes were to be used to develop clinical tests.
In summary, patients with recent TIAs can be differentiated from controls without previous vascular events using gene expression profiles in blood. In addition, there may be different immune response subtypes following transient ischemic attacks in humans.
Table 5. TIA associated gene lists (FDR≦5.05, absolute fold change≧1.5 compared with control).

TABLE 5A

Table 5A. 135 Downregulated Genes

			Fold-
AFFY ID	Gene Symbol	Gene Title	Change

233034_at	—	—	−2.44997
237597_at	—	—	−2.4398
1558409_at	—	—	−2.26242
1566485_at	—	—	−2.22393
1556932_at	—	—	−2.11785
242874_at	—	—	−2.03355
1561166_a_at	—	—	−1.9781
217671_at	—	—	−1.9453
1557733_a_at	—	—	−1.91008
1557580_at	—	—	−1.85725
1558410_s_at	—	—	−1.7902
242710_at	—	—	−1.76712
215314_at	—	—	−1.75283
229654_at	—	—	−1.74432
1560861_at	—	—	−1.74348
243512_x_at	—	—	−1.73922
238812_at	—	—	−1.70108
232943_at	—	—	−1.69925
233677_at	—	—	−1.68615
244226_s_at	—	—	−1.68579
233614_at	—	—	−1.68298
1557581_x_at	—	—	−1.67676
244860_at	—	—	−1.67397
239588_s_at	—	—	−1.667
244665_at	—	—	−1.65812
243107_at	—	—	−1.65279
1557519_at	—	—	−1.64084
242564_at	—	—	−1.63967
1557551_at	—	—	−1.63028
238281_at	—	—	−1.62416
1558710_at	—	—	−1.62037
239646_at	—	—	−1.60914
1568781_at	—	—	−1.60862
234148_at	—	—	−1.60079
233302_at	—	—	−1.59557
233862_at	—	—	−1.58604
1570329_at	—	—	−1.56927
241638_at	—	—	−1.56143
232834_at	—	—	−1.559
236524_at	—	—	−1.55759
1559723_s_at	—	—	−1.55744
1559401_a_at	—	—	−1.55691
236558_at	—	—	−1.55664
237803_x_at	—	—	−1.55619
231069_at	—	—	−1.5535
1557477_at	—	—	−1.54943
237953_at	—	—	−1.54815
243641_at	—	—	−1.547
1555194_at	—	—	−1.54304
217060_at	—	—	−1.54232
239449_at	—	—	−1.54082
237334_at	—	—	−1.53953
242074_at	—	—	−1.53917
1570106_at	—	—	−1.53564
244674_at	—	—	−1.53173
232372_at	—	—	−1.52446
238744_at	—	—	−1.52032
233127_at	—	—	−1.5089
243310_at	—	—	−1.50605
214309_s_at	—	—	−1.50383
244290_at	—	—	−1.50381
1562013_a_at	—	—	−1.50343
219308_s_at	AK5	adenylate kinase 5	−1.95614
222862_s_at	AK5	adenylate kinase 5	−1.64741
239651_at	ANAPC5	anaphase promoting complex subunit 5	−1.55844
209871_s_at	APBA2	amyloid beta (A4) precursor protein-binding, family A,	−1.56895
		member 2
229252_at	ATG9B	ATG9 autophagy related 9 homolog B (S. cerevisiae)	−1.64694
227372_s_at	BAIAP2L1 ///	BAI1-associated protein 2-like 1 /// hypothetical protein	−1.53271
	LOC100128461	LOC100128461
221631_at	CACNA1I	calcium channel, voltage-dependent, T type, alpha II	−1.63297
		subunit
239771_at	CAND1	cullin-associated and neddylation-dissociated 1	−1.97531
1553645_at	CCDC141	coiled-coil domain containing 141	−1.62867
1562028_at	CCND3	Cyclin D3 (CCND3), transcript variant 3, mRNA	−2.00377
239871_at	CLTC	Clathrin, heavy chain (Hc), mRNA (cDNA clone	−1.63031
		IMAGE: 4812912)
212504_at	DIP2C	DIP2 disco-interacting protein 2 homolog C (Drosophila)	−1.62614
1553998_at	DMRTC1 ///	DMRT-like family C1 /// DMRT-like family C1B	−1.86704
	DMRTC1B
220048_at	EDAR	ectodysplasin A receptor	−1.69385
209368_at	EPHX2	epoxide hydrolase 2, cytoplasmic	−1.62474
1554273_a_at	ERAP2	endoplasmic reticulum aminopeptidase 2	−1.52883
230792_at	FAAH2	fatty acid amide hydrolase 2	−1.57807
229247_at	FBLN7	fibulin 7	−1.58734
202768_at	FOSB	FBJ murine osteosarcoma viral oncogene homolog B	−1.63049
231108_at	FUS	fusion (involved in t(12; 16) in malignant liposarcoma)	−1.56277
1557350_at	G3BP1	GTPase activating protein (SH3 domain) binding protein 1	−1.6194
219815_at	GAL3ST4	galactose-3-O-sulfotransferase 4	−1.5674
1560133_at	GIGYF2	GRB10 interacting GYF protein 2	−1.52626
223080_at	GLS	Glutaminase, mRNA (cDNA clone MGC: 33744	−1.59404
		IMAGE: 5263220)
221288_at	GPR22	G protein-coupled receptor 22	−1.56303
215333_x_at	GSTM1	glutathione S-transferase mu 1	−2.03103
204550_x_at	GSTM1	glutathione S-transferase mu 1	−1.95136
204418_x_at	GSTM2	glutathione S-transferase mu 2 (muscle)	−1.95729
232207_at	GUSBL2	glucuronidase, beta-like 2	−2.10621
220085_at	HELLS	helicase, lymphoid-specific	−1.67692
241723_at	IQGAP2	IQ motif containing GTPase activating protein 2	−1.73571
215750_at	KIAA1659	KIAA1659 protein	−1.54646
236728_at	LNPEP	leucyl/cystinyl aminopeptidase	−1.53387
236621_at	LOC100130070 ///	similar to metallopanstimulin /// similar to rCG63653 ///	−1.70558
	LOC100130775 ///	similar to metallopans
	LOC100131787 ///
	LOC100131905 ///
	LOC100132291 ///
	LOC100132488 ///
	RPS27
239062_at	LOC100131096	hypothetical LOC100131096	−1.57675
229094_at	LOC401431	hypothetical gene LOC401431	−1.53069
1565911_at	LOC648921	MRNA full length insert cDNA clone EUROIMAGE	−1.54981
		209544
214180_at	MAN1C1	mannosidase, alpha, class 1C, member 1	−1.66631
215663_at	MBNL1	muscleblind-like (Drosophila)	−1.53726
212935_at	MCF2L	MCF.2 cell line derived transforming sequence-like	−1.53863
207078_at	MED6	mediator complex subunit 6	−1.53192
242111_at	METTL3	methyltransferase like 3	−1.56742
1559856_s_at	MLL	myeloid/lymphoid or mixed-lineage leukemia (trithorax	−1.59219
		homolog, Drosophila)
243857_at	MORF4L2	Mrgx mRNA for MRGX	−1.52328
242191_at	NBPF10 /// RP11-	neuroblastoma breakpoint family, member 10 ///	−1.50043
	9412.2	hypothetical protein LOC200030
203413_at	NELL2	NEL-like 2 (chicken)	−1.5281
229093_at	NOS3	nitric oxide synthase 3 (endothelial cell)	−1.53818
223601_at	OLFM2	olfactomedin 2	−1.5119
214615_at	P2RY10	purinergic receptor P2Y, G-protein coupled, 10	−1.51779
235758_at	PNMA6A	paraneoplastic antigen like 6A	−1.95731
244011_at	PPM1K	protein phosphatase 1K (PP2C domain containing)	−1.51501
239635_at	RBM14	RNA binding motif protein 14	−1.65349
219864_s_at	RCAN3	RCAN family member 3	−1.61977
212699_at	SCAMP5	secretory carrier membrane protein 5	−1.54948
232055_at	SFXN1	sideroflexin 1	−1.50117
239667_at	SLC3A1	solute carrier family 3 (cystine, dibasic and neutral amino	−1.69708
		acid transporters, a
1553423_a_at	SLFN13	schlafen family member 13	−1.53028
232020_at	SMURF2	SMAD specific E3 ubiquitin protein ligase 2	−1.57992
1560741_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	−1.65945
226587_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	−1.58006
226913_s_at	SOX8	SRY (sex determining region Y)-box 8	−1.73755
1555882_at	SPIN3	spindlin family, member 3	−1.65127
1555883_s_at	SPIN3	spindlin family, member 3	−1.50348
213993_at	SPON1	spondin 1, extracellular matrix protein	−1.55928
218856_at	TNFRSF21	tumor necrosis factor receptor superfamily, member 21	−1.77712
1556116_s_at	TNPO1	Transportin 1, mRNA (cDNA clone MGC: 17116	−1.7577
		IMAGE: 4178989)
244521_at	TSHZ2	Cell growth-inhibiting protein 7	−1.86192
206487_at	UNC84A	unc-84 homolog A (C. elegans)	−1.50376
1558569_at	UNQ6228	MRNA; cDNA DKFZp667K1619 (from clone	−1.63796
		DKFZp667K1619)
1557450_s_at	WHDC1L2	WAS protein homology region 2 domain containing 1-	−1.75555
		like 2
229234_at	ZC3H12B	zinc finger CCCH-type containing 12B	−1.72127
55872_at	ZNF512B	zinc finger protein 512B	−1.52158
1568873_at	ZNF519	zinc finger protein 519	−1.70283

TABLE 5B

Table 5B. 325 Upregulated Genes

			Fold-
AFFY ID	Gene Symbol	Gene Title	Change

1563546_at	—	—	3.50048
1559696_at	—	—	3.23854
1563033_x_at	—	—	3.16355
1563032_at	—	—	2.97375
1558496_at	—	—	2.87094
241566_at	—	—	2.82164
1568589_at	—	—	2.7205
215448_at	—	—	2.69149
237479_at	—	—	2.68144
234235_at	—	—	2.64462
231074_at	—	—	2.63519
1560905_at	—	—	2.63286
237871_x_at	—	—	2.55976
237937_x_at	—	—	2.541
207731_at	—	—	2.52426
240988_x_at	—	—	2.46734
243398_at	—	—	2.43872
241675_s_at	—	—	2.39854
241674_s_at	—	—	2.38362
228827_at	—	—	2.3697
233944_at	—	—	2.36679
227952_at	—	—	2.31481
1554225_a_at	—	—	2.30748
1560049_at	—	—	2.29877
215962_at	—	—	2.28524
1564306_at	—	—	2.20443
1557762_at	—	—	2.18276
231091_x_at	—	—	2.17817
1566862_at	—	—	2.1529
1560760_s_at	—	—	2.1184
230959_at	—	—	2.10492
238103_at	—	—	2.08283
242802_x_at	—	—	2.06924
234502_at	—	—	2.05567
241636_x_at	—	—	2.0384
236038_at	—	—	2.0344
216406_at	—	—	2.02612
1566805_at	—	—	2.00292
239464_at	—	—	2.00073
233875_at	—	—	1.99361
1561713_at	—	—	1.9693
1562480_at	—	—	1.94431
1556983_a_at	—	—	1.93605
1570191_at	—	—	1.93494
243902_at	—	—	1.93045
207744_at	—	—	1.92381
237233_at	—	—	1.90496
1561199_at	—	—	1.89756
1561902_at	—	—	1.89021
243273_at	—	—	1.88315
238368_at	—	—	1.88178
243666_at	—	—	1.87601
1556989_at	—	—	1.86984
238358_x_at	—	—	1.86726
229635_at	—	—	1.8637
238361_s_at	—	—	1.84576
231503_at	—	—	1.84378
229490_s_at	—	—	1.84229
1569344_a_at	—	—	1.83229
234083_at	—	—	1.83201
243183_at	—	—	1.83176
238405_at	—	—	1.82494
1559336_at	—	—	1.82388
1563568_at	—	—	1.81339
237983_at	—	—	1.81139
1563881_at	—	—	1.801
242198_at	—	—	1.79799
1562613_at	—	—	1.78841
1560086_at	—	—	1.78528
237893_at	—	—	1.77856
1562992_at	—	—	1.75888
240112_at	—	—	1.75583
1569810_at	—	—	1.75522
1566609_at	—	—	1.75501
243533_x_at	—	—	1.74919
1570152_at	—	—	1.74489
1561112_at	—	—	1.74035
231040_at	—	—	1.73604
1559695_a_at	—	—	1.7325
1560296_at	—	—	1.72689
1561473_at	—	—	1.72375
241654_at	—	—	1.71535
1557645_at	—	—	1.70892
1566498_at	—	—	1.70831
237399_at	—	—	1.70373
1562811_at	—	—	1.70357
1561448_at	—	—	1.68957
237933_at	—	—	1.68559
241457_at	—	—	1.67974
242420_at	—	—	1.67555
222342_at	—	—	1.6753
1556021_at	—	—	1.67385
239984_at	—	—	1.67188
244216_at	—	—	1.67082
234794_at	—	—	1.66748
215290_at	—	—	1.65929
243279_at	—	—	1.65749
1570268_at	—	—	1.65328
244384_at	—	—	1.65237
238571_at	—	—	1.64715
237552_at	—	—	1.64653
241461_at	—	—	1.63938
242718_at	—	—	1.63417
238392_at	—	—	1.62252
238354_x_at	—	—	1.62228
1560453_at	—	—	1.62059
215976_at	—	—	1.62035
1564840_at	—	—	1.6194
1561767_at	—	—	1.61738
1553275_s_at	—	—	1.61253
1563087_at	—	—	1.61106
1566597_at	—	—	1.59925
244668_at	—	—	1.59371
216518_at	—	—	1.5937
1563561_at	—	—	1.59351
236571_at	—	—	1.5893
216214_at	—	—	1.58555
240904_at	—	—	1.58293
235494_at	—	—	1.57849
240067_at	—	—	1.57319
237071_at	—	—	1.57301
233306_at	—	—	1.56521
216463_at	—	—	1.56326
237192_at	—	—	1.56114
1560517_s_at	—	—	1.55983
1555263_at	—	—	1.556
1566968_at	—	—	1.55262
241173_at	—	—	1.54723
1561351_at	—	—	1.54685
1559629_at	—	—	1.54679
238395_at	—	—	1.54457
1563026_at	—	—	1.54135
1562610_at	—	—	1.53899
1570506_at	—	—	1.53071
231546_at	—	—	1.52352
240714_at	—	—	1.52183
242495_at	—	—	1.51926
1561642_at	—	—	1.51919
234825_at	—	—	1.51483
241247_at	—	—	1.51115
236276_at	—	—	1.50976
238386_x_at	—	—	1.50861
241569_at	—	—	1.50674
1564851_at	—	—	1.50551
1556185_a_at	—	—	1.50406
243424_at	—	—	1.50374
238274_at	—	—	1.50237
207275_s_at	ACSL1	acyl-CoA synthetase long-chain family member 1	1.51866
243520_x_at	ADAM30	ADAM metallopeptidase domain 30	1.80193
206134_at	ADAMDEC1	ADAM-like, decysin 1	1.61274
209614_at	ADH1B	alcohol dehydrogenase 1B (class I), beta polypeptide	1.51397
202912_at	ADM	adrenomedullin	1.61874
206513_at	AIM2	absent in melanoma 2	1.60396
215783_s_at	ALPL	alkaline phosphatase, liver/bone/kidney	2.1006
1557924_s_at	ALPL	alkaline phosphatase, liver/bone/kidney	2.02022
1563673_a_at	ALS2CR11	amyotrophic lateral sclerosis 2 (juvenile) chromosome	2.15177
		region, candidate 11
1562292_at	ANKRD30B	ankyrin repeat domain 30B	1.86641
209369_at	ANXA3	annexin A3	2.41095
1554816_at	ASTN2	astrotactin 2	2.22748
239144_at	B3GAT2	beta-1,3-glucuronyltransferase 2 (glucuronosyltransferase	1.75721
		S)
228758_at	BCL6	Zinc finger protein	1.69127
215990_s_at	BCL6	B-cell CLL/lymphoma 6	1.59315
242579_at	BMPR1B	bone morphogenetic protein receptor, type IB	2.05687
232416_at	BRUNOL5	bruno-like 5, RNA binding protein (Drosophila)	1.68747
223977_s_at	C18orf2	chromosome 18 open reading frame 2	1.58384
1553652_a_at	C18orf54	chromosome 18 open reading frame 54	1.54796
235568_at	C19orf59	chromosome 19 open reading frame 59	1.99789
1554540_at	C1orf67	chromosome 1 open reading frame 67	1.51941
1553329_at	C7orf45	chromosome 7 open reading frame 45	1.72974
239203_at	C7orf53	chromosome 7 open reading frame 53	1.55912
1552701_a_at	CARD16	caspase recruitment domain family, member 16	1.59587
232969_at	CARD8	caspase recruitment domain family, member 8	1.78265
207500_at	CASP5	caspase 5, apoptosis-related cysteine peptidase	1.91798
203065_s_at	CAV1	caveolin 1, caveolae protein, 22 kDa	1.60773
220351_at	CCRL1	chemokine (C-C motif) receptor-like 1	2.32444
208168_s_at	CHIT1	chitinase 1 (chitotriosidase)	1.56138
239989_at	CNTLN	centlein, centrosomal protein	1.53478
229084_at	CNTN4	contactin 4	1.7244
1556499_s_at	COL1A1	collagen, type I, alpha 1	2.87107
229218_at	COL1A2	collagen, type I, alpha 2	1.92067
210262_at	CRISP2	cysteine-rich secretory protein 2	1.88349
1553002_at	DEFB105A ///	defensin, beta 105A /// defensin, beta 105B	1.52948
	DEFB105B
226121_at	DHRS13	dehydrogenase/reductase (SDR family) member 13	1.65414
233092_s_at	DKFZP434B061	DKFZP434B061 protein	1.84946
222253_s_at	DKFZP434P211	POM121 membrane glycoprotein-like 1 pseudogene	2.61011
206819_at	DKFZP434P211	POM121 membrane glycoprotein-like 1 pseudogene	1.93567
239309_at	DLX6	distal-less homeobox 6	2.4523
220493_at	DMRT1	doublesex and mab-3 related transcription factor 1	1.61917
241199_x_at	DPPA4	developmental pluripotency associated 4	2.68174
232360_at	EHF	ets homologous factor	1.68951
219850_s_at	EHF	ets homologous factor	1.64412
228260_at	ELAVL2	ELAV (embryonic lethal, abnormal vision, Drosophila)-	1.9905
		like 2 (Hu antigen B)
227612_at	ELAVL3	ELAV (embryonic lethal, abnormal vision, Drosophila)-	3.23425
		like 3 (Hu antigen C)
219134_at	ELTD1	EGF, latrophilin and seven transmembrane domain	1.70282
		containing 1
211164_at	EPHA3	EPH receptor A3	2.39314
243277_x_at	EVI1	ecotropic viral integration site 1	1.5445
230519_at	FAM124A	family with sequence similarity 124A	1.59499
1569025_s_at	FAM13A1	family with sequence similarity 13, member A1	1.55876
222291_at	FAM149A	family with sequence similarity 149, member A	1.75785
222205_x_at	FAM182B /// RP13-	family with sequence similarity 182, member B ///	1.70042
	401N8.2	hypothetical gene supported by
220645_at	FAM55D	family with sequence similarity 55, member D	1.55166
201579_at	FAT1	FAT tumor suppressor homolog 1 (Drosophila)	1.67288
239710_at	FIGN	fidgetin	2.14096
238964_at	FIGN	fidgetin	1.56796
1557155_a_at	FLJ30375	CDNA clone IMAGE: 5301781	1.97451
229521_at	FLJ36031	hypothetical protein FLJ36031	1.58141
1560790_at	FLJ36144	hypothetical protein FLJ36144	1.78391
1558579_at	FLJ37786	hypothetical LOC642691	1.66029
230999_at	FLJ39051	CDNA FLJ39051 fis, clone NT2RP7011452	1.92605
227925_at	FLJ39051	CDNA FLJ39051 fis, clone NT2RP7011452	1.86433
217487_x_at	FOLH1	folate hydrolase (prostate-specific membrane antigen) 1	2.19987
217483_at	FOLH1	folate hydrolase (prostate-specific membrane antigen) 1	1.68955
40284_at	FOXA2	forkhead box A2	1.8498
1553613_s_at	FOXC1	forkhead box C1	1.53964
230964_at	FREM2	FRAS1 related extracellular matrix protein 2	2.30984
1553024_at	G30	protein LG30-like	1.75094
1557122_s_at	GABRB2	gamma-aminobutyric acid (GABA) A receptor, beta 2	3.49668
242344_at	GABRB2	gamma-aminobutyric acid (GABA) A receptor, beta 2	2.72458
1555726_at	GAFA3	FGF-2 activity-associated protein 3	1.61768
219271_at	GALNT14	UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-	2.07605
		acetylgalactosaminyltransferase
240390_at	GALNT5	UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-	2.09257
		acetylgalactosaminyltransferase
204763_s_at	GNAO1	guanine nucleotide binding protein (G protein), alpha	1.5542
		activating activity polype
223767_at	GPR84	G protein-coupled receptor 84	1.76044
207235_s_at	GRM5	glutamate receptor, metabotropic 5	1.93451
1559520_at	GYPA	Glycophorin A	2.12904
211267_at	HESX1	HESX homeobox 1	1.61355
227566_at	HNT	neurotrimin	1.56554
206858_s_at	HOXC4 /// HOXC6	homeobox C4 /// homeobox C6	1.70414
219403_s_at	HPSE	heparanase	1.60481
211959_at	IGFBP5	insulin-like growth factor binding protein 5	1.54545
205067_at	IL1B	interleukin 1, beta	1.57884
39402_at	IL1B	interleukin 1, beta	1.51316
229538_s_at	IQGAP3	IQ motif containing GTPase activating protein 3	1.73797
214927_at	ITGBL1	integrin, beta-like 1 (with EGF-like repeat domains)	1.73813
238428_at	KCNJ15 //	potassium inwardly-rectifying channel, subfamily J,	1.56965
	LOC100131955	member 15 /// similar to pot
227250_at	KREMEN1	kringle containing transmembrane protein 1	2.16406
235370_at	KREMEN1	kringle containing transmembrane protein 1	1.77475
215516_at	LAMB4	laminin, beta 4	1.60646
206140_at	LHX2	LIM homeobox 2	2.0959
225571_at	LIFR	leukemia inhibitory factor receptor alpha	1.69168
210582_s_at	LIMK2	LIM domain kinase 2	1.5485
1556704_s_at	LOC100133920 ///	hypothetical protein LOC100133920 /// hypothetical	1.63034
	LOC286297	protein LOC286297
232034_at	LOC203274	CDNA FLJ31544 fis, clone NT2RI2000865	1.63147
1557717_at	LOC338862	hypothetical protein LOC338862	2.22946
1560823_at	LOC340017	hypothetical protein LOC340017	1.51946
233879_at	LOC374491	TPTE and PTEN homologous inositol lipid phosphatase	1.81019
		pseudogene
1558982_at	LOC375010	hypothetical LOC375010	1.72485
214984_at	LOC440345	hypothetical protein LOC440345	1.98536
230902_at	LOC645323	CDNA clone IMAGE: 5260726	1.84336
238850_at	LOC645323	hypothetical LOC645323	1.81503
1568933_at	LOC646627	phospholipase inhibitor	1.53874
231434_at	LOC728460	similar to FLJ32921 protein	1.68733
1570009_at	LOC732096	similar to hCG2040240	2.13184
230863_at	LRP2	low density lipoprotein-related protein 2	1.71146
203005_at	LTBR	lymphotoxin beta receptor (TNFR superfamily, member	1.58399
		3)
201744_s_at	LUM	lumican	1.93131
210449_x_at	MAPK14	mitogen-activated protein kinase 14	1.57327
211561_x_at	MAPK14	mitogen-activated protein kinase 14	1.55337
235077_at	MEG3	maternally expressed 3 (non-protein coding)	1.6384
240814_at	MGC39584	hypothetical gene supported by BC029568	1.59341
214087_s_at	MYBPC1	myosin binding protein C, slow type	1.58609
237510_at	MYNN	Myoneurin, mRNA (cDNA clone IMAGE: 4721583)	1.85041
1559292_s_at	NCRNA00032	Clone IMAGE: 2275835 C9orf14 mRNA, partial	1.98554
		sequence, alternatively spliced
220429_at	NDST3	N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3	1.68889
209119_x_at	NR2F2	nuclear receptor subfamily 2, group F, member 2	1.94377
231867_at	ODZ2	odz, odd Oz/ten-m homolog 2 (Drosophila)	2.03143
214111_at	OPCML	opioid binding protein/cell adhesion molecule-like	1.91158
230170_at	OSM	oncostatin M	1.58899
1553931_at	OSTCL	oligosaccharyltransferase complex subunit-like	1.57501
206048_at	OVOL2	ovo-like 2 (Drosophila)	2.06333
1559400_s_at	PAPPA	pregnancy-associated plasma protein A, pappalysin 1	1.50009
210292_s_at	PCDH11X ///	protocadherin 11 X-linked /// protocadherin 11 Y-linked	1.6605
	PCDH11Y
208396_s_at	PDE1A	phosphodiesterase 1A, calmodulin-dependent	1.68453
214868_at	PIWIL1	piwi-like 1 (Drosophila)	1.63171
202446_s_at	PLSCR1	phospholipid scramblase 1	1.54059
233030_at	PNPLA3	patatin-like phospholipase domain containing 3	1.50269
1569675_at	POU2AF1	POU class 2 associating factor 1, mRNA (cDNA clone	1.67876
		MGC: 45211 IMAGE: 5554134)
1555462_at	PPP1R1C	protein phosphatase 1, regulatory (inhibitor) subunit 1C	1.60542
241669_x_at	PRKD2	protein kinase D2	1.55139
220696_at	PRO0478	PRO0478 protein	1.69169
228825_at	PTGR1	prostaglandin reductase 1	1.95262
217194_at	RASAL2	RAS protein activator like 2	2.00632
226872_at	RFX2	regulatory factor X, 2 (influences HLA class II	1.58786
		expression)
213194_at	ROBO1	roundabout, axon guidance receptor, homolog 1	1.95207
		(Drosophila)
242385_at	RORB	RAR-related orphan receptor B	2.14023
1555990_at	RP1-127L4.6	hypothetical protein LOC150297	1.76603
215321_at	RUNDC3B	RUN domain containing 3B	1.60322
205863_at	S100A12	S100 calcium binding protein A12	1.5633
229057_at	SCN2A	sodium channel, voltage-gated, type II, alpha subunit	1.85129
207570_at	SHOX	short stature homeobox	2.00103
210135_s_at	SHOX2	short stature homeobox 2	2.86893
208443_x_at	SHOX2	short stature homeobox 2	1.70616
206634_at	SIX3	SIX homeobox 3	1.78989
205896_at	SLC22A4	solute carrier family 22 (organic cation/ergothioneine	1.65918
		transporter), member 4
237340_at	SLC26A8	solute carrier family 26, member 8	2.32491
216236_s_at	SLC2A14 ///	solute carrier family 2 (facilitated glucose transporter),	1.51356
	SLC2A3	member 14 /// solute
232547_at	SNIP	SNAP25-interacting protein	1.83841
240204_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	1.58295
241987_x_at	SNX31	sorting nexin 31	2.19167
204913_s_at	SOX11	SRY (sex determining region Y)-box 11	2.34727
204914_s_at	SOX11	SRY (sex determining region Y)-box 11	1.88201
202935_s_at	SOX9	SRY (sex determining region Y)-box 9	2.45928
235342_at	SPOCK3	sparc/osteonectin, cwcv and kazal-like domains	1.75314
		proteoglycan (testican) 3
241961_at	SRD5A2L2	steroid 5 alpha-reductase 2-like 2	2.08494
1554473_at	SRGAP1	SLIT-ROBO Rho GTPase activating protein 1	1.99203
203759_at	ST3GAL4	ST3 beta-galactoside alpha-2,3-sialyltransferase 4	1.51002
231969_at	STOX2	storkhead box 2	2.2552
214451_at	TFAP2B	transcription factor AP-2 beta (activating enhancer	1.89347
		binding protein 2 beta)
215447_at	TFPI	Tissue factor pathway inhibitor (lipoprotein-associated	1.96509
		coagulation inhibitor),
228121_at	TGFB2	transforming growth factor, beta 2	1.70904
210166_at	TLR5	toll-like receptor 5	1.9168
220205_at	TPTE	transmembrane phosphatase with tensin homology	1.60547
206479_at	TRPM1	transient receptor potential cation channel, subfamily M,	1.57541
		member 1
1556666_a_at	TTC6	tetratricopeptide repeat domain 6	1.91015
213943_at	TWIST1	twist homolog 1 (Drosophila)	2.72279
222435_s_at	UBE2J1	ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog,	1.50758
		yeast)
226899_at	UNC5B	unc-5 homolog B (C. elegans)	2.04351
1561200_at	VWA3B	von Willebrand factor A domain containing 3B	1.61802
206954_at	WIT1	Wilms tumor upstream neighbor 1	2.58643
1552946_at	ZNF114	zinc finger protein 114	1.99445
229743_at	ZNF438	zinc finger protein 438	1.53049
244007_at	ZNF462	zinc finger protein 462	1.53545
1555367_at	ZNF479	zinc finger protein 479	2.25193
1555368_x_at	ZNF479	zinc finger protein 479	2.16203
232303_at	ZNF608	zinc finger protein 608	1.72629

TABLE 5C

34 Genes that differentiate TIA from Control

			Fold-
AFFY ID	Gene Symbol	Gene Title	Change

1557580_at	—	—	−1.85725
1559695_a_at	—	—	1.7325
1561767_at	—	—	1.61738
1563026_at	—	—	1.54135
1563568_at	—	—	1.81339
1568589_at	—	—	2.7205
1568781_at	—	—	−1.60862
216406_at	—	—	2.02612
229654_at	—	—	−1.74432
231040_at	—	—	1.73604
231069_at	—	—	−1.5535
231546_at	—	—	1.52352
233306_at	—	—	1.56521
236571_at	—	—	1.5893
237597_at	—	—	−2.4398
237953_at	—	—	−1.54815
242495_at	—	—	1.51926
242564_at	—	—	−1.63967
242710_at	—	—	−1.76712
244226_s_at	—	—	−1.68579
244665_at	—	—	−1.65812
229252_at	ATG9B	ATG9 autophagy	−1.64694
		related 9 homolog B
		(S. cerevisiae)
212504_at	DIP2C	DIP2 disco-interacting	−1.62614
		protein 2 homolog C
		(Drosophila)
233092_s_at	DKFZP434B061	DKFZP434B061 protein	1.84946
220048_at	EDAR	ectodysplasin A receptor	−1.69385
220645_at	FAM55D	family with sequence	1.55166
		similarity 55, member D
1557155_a_at	FLJ30375	CDNA clone IMAGE:	1.97451
		5301781
215333_x_at	GSTM1	glutathione S-transferase	−2.03103
		mu 1
232207_at	GUSBL2	glucuronidase, beta-like	−2.10621
		2
211959_at	IGFBP5	insulin-like growth factor	1.54545
		binding protein 5
203005_at	LTBR	lymphotoxin beta	1.58399
		receptor (TNFR
		superfamily, member 3)
229057_at	SCN2A	sodium channel, voltage-	1.85129
		gated, type II, alpha
		subunit
232020_at	SMURF2	SMAD specific E3	−1.57992
		ubiquitin protein ligase 2
55872_at	ZNF512B	zinc finger protein 512B	−1.52158

TABLE 5D

26 Upregulated Genes that differentiate TIA1 from TIA2

			Fold-
AFFY ID	Gene Symbol	Gene Title	Change

1557122_s_at	GABRB2	gamma-aminobutyric acid	3.49668
		(GABA) A receptor, beta 2
1559696_at	—	—	3.23854
227612_at	ELAVL3	ELAV (embryonic lethal,	3.23425
		abnormal vision,
		Drosophila)-like 3
		(Hu antigen C)
1563032_at	—	—	2.97375
1558496_at	—	—	2.87094
241566_at	—	—	2.82164
213943_at	TWIST1	twist homolog	1	2.72279
		(Drosophila)
215448_at	—	—	2.69149
241199_x_at	DPPA4	developmental pluripotency	2.68174
		associated 4
237479_at	—	—	2.68144
234235_at	—	—	2.64462
1560905_at	—	—	2.63286
222253_s_at	DKFZP434P211	POM121 membrane	2.61011
		glycoprotein-like 1
		pseudogene
237937_x_at	—	—	2.541
207731_at	—	—	2.52426
239309_at	DLX6	distal-less homeobox 6	2.4523
243398_at	—	—	2.43872
241675_s_at	—	—	2.39854
241674_s_at	—	—	2.38362
1555367_at	ZNF479	zinc finger protein 479	2.25193
1554816_at	ASTN2	astrotactin 2	2.22748
241987_x_at	SNX31	sorting nexin 31	2.19167
1557762_at	—	—	2.18276
1563673_a_at	ALS2CR11	amyotrophic lateral	2.15177
		sclerosis 2 (juvenile)
		chromosome region,
		candidate 11
214984_at	LOC440345	hypothetical protein	1.98536
		LOC440345
1556983_a_at	—	—	1.93605

TABLE 8

Table 8 - Significant genes between TIA1 and TIA2 (FDR ≦ 0.05, absolute fold change ≧ 1.5, TIA1 vs TIA2)

			Fold
AFFY ID	Gene Symbol	Gene Title	Change

1553422_s_at	A2BP1	ataxin 2-binding protein 1	1.72186
223593_at	AADAT	aminoadipate aminotransferase	1.85564
214829_at	AASS	aminoadipate-semialdehyde synthase	1.89032
1552582_at	ABCC13	ATP-binding cassette, sub-family C (CFTR/MRP), member 13	2.62247
1557374_at	ABCC9	ATP-binding cassette, sub-family C (CFTR/MRP), member 9	1.74138
208462_s_at	ABCC9	ATP-binding cassette, sub-family C (CFTR/MRP), member 9	2.03195
220518_at	ABI3BP	ABI family, member 3 (NESH) binding protein	1.81797
220061_at	ACSM5	acyl-CoA synthetase medium-chain family member 5	1.74065
89977_at	ACSM5	acyl-CoA synthetase medium-chain family member 5	2.18846
215613_at	ADAM12	Meltrin-S (ADAM12) mRNA, complete cds, alternatively spliced	1.79057
1568970_at	ADAM18	ADAM metallopeptidase domain 18	2.48574
207664_at	ADAM2	ADAM metallopeptidase domain 2	1.9154
243520_x_at	ADAM30	ADAM metallopeptidase domain 30	2.74216
1552266_at	ADAM32	ADAM metallopeptidase domain 32	1.65164
206134_at	ADAMDEC1	ADAM-like, decysin 1	3.08521
230040_at	ADAMTS18	ADAM metallopeptidase with thrombospondin type 1 motif, 18	1.68813
1553180_at	ADAMTS19	ADAM metallopeptidase with thrombospondin type 1 motif, 19	2.44377
214913_at	ADAMTS3	ADAM metallopeptidase with thrombospondin type 1 motif, 3	1.58473
220287_at	ADAMTS9	ADAM metallopeptidase with thrombospondin type 1 motif, 9	1.97398
209614_at	ADH1B	alcohol dehydrogenase 1B (class I), beta polypeptide	1.60016
231678_s_at	ADH4	alcohol dehydrogenase 4 (class II), pi polypeptide	1.66033
204120_s_at	ADK	adenosine kinase	−1.79666
211491_at	ADRA1A	adrenergic, alpha-1A-, receptor	1.6033
204333_s_at	AGA	aspartylglucosaminidase	−1.54576
1553447_at	AGBL1	ATP/GTP binding protein-like 1	1.51198
1554820_at	AGBL3	ATP/GTP binding protein-like 3	1.79467
232007_at	AGPAT5	1-acylglycerol-3-phosphate O-acyltransferase 5 (lysophosphatidic	−1.78587
		acid acyltransf
205357_s_at	AGTR1	angiotensin II receptor, type 1	1.51953
206957_at	AGXT	alanine-glyoxylate aminotransferase	1.50599
230630_at	AK3L1 ///	adenylate kinase 3-like 1 /// adenylate kinase 3-like 2	1.52481
	AK3L2
207870_at	AKAP9	A kinase (PRKA) anchor protein (yotiao) 9	1.76652
244205_at	ALAS2	aminolevulinate, delta-, synthase 2	1.67115
211617_at	ALDOAP2	aldolase A, fructose-bisphosphate pseudogene 2	3.07845
211357_s_at	ALDOB	aldolase B, fructose-bisphosphate	1.74204
1553261_x_at	ALS2CR11	amyotrophic lateral sclerosis 2 (juvenile) chromosome region,	2.08857
		candidate 11
1553260_s_at	ALS2CR11	amyotrophic lateral sclerosis 2 (juvenile) chromosome region,	2.81678
		candidate 11
1563673_a_at	ALS2CR11	amyotrophic lateral sclerosis 2 (juvenile) chromosome region,	3.60798
		candidate 11
1553471_at	AMAC1	acyl-malonyl condensing enzyme 1	1.53576
236760_at	AMMECR1	Alport syndrome, mental retardation, midface hypoplasia and	−1.61791
		elliptocytosis chrom
203002_at	AMOTL2	angiomotin like 2	1.52446
243799_x_at	ANGPTL3	Angiopoietin-like 3, mRNA (cDNA clone IMAGE: 3934961)	1.63129
232606_at	ANK2	Ankyrin, Brank-1 protein	1.69608
1553211_at	ANKFN1	ankyrin-repeat and fibronectin type III domain containing 1	1.66982
1560370_x_at	ANKH	CDNA FLJ30404 fis, clone BRACE2008481	1.53577
243181_at	ANKIB1	ankyrin repeat and IBR domain containing 1	−1.59952
206029_at	ANKRD1	ankyrin repeat domain 1 (cardiac muscle)	1.58224
1559406_at	ANKRD18A	ankyrin repeat domain 18A	1.76934
1570255_s_at	ANKRD20A1	ankyrin repeat domain 20 family, member A1 /// ankyrin repeat	2.65731
	///	domain 20 family,
	ANKRD20A2
	///
	ANKRD20A3
	///
	ANKRD20A4
	/// ANKRD20B
	/// LOC375010
	/// LOC647595
	/// LOC728371
205706_s_at	ANKRD26	ankyrin repeat domain 26	−1.69786
1561079_at	ANKRD28	ankyrin repeat domain 28	1.96635
1562292_at	ANKRD30B	ankyrin repeat domain 30B	2.5644
1562294_x_at	ANKRD30B	ankyrin repeat domain 30B	3.18306
227034_at	ANKRD57	ankyrin repeat domain 57	−1.62847
213553_x_at	APOC1	apolipoprotein C-I	1.51627
215931_s_at	ARFGEF2	ADP-ribosylation factor guanine nucleotide-exchange factor 2	−1.50024
		(brefeldin A-inhibi
228368_at	ARHGAP20	Rho GTPase activating protein 20	1.60285
1560318_at	ARHGAP29	Rho GTPase activating protein 29	4.60468
235412_at	ARHGEF7	Rho guanine nucleotide exchange factor (GEF) 7 (ARHGEF7),	1.63916
		transcript variant 2,
242727_at	ARL5B	ADP-ribosylation factor-like 5B	−1.54355
219094_at	ARMC8	armadillo repeat containing 8	−1.57518
227444_at	ARMCX4	Armadillo repeat containing, X-linked 4, mRNA (cDNA clone	−1.81523
		IMAGE: 5261888)
239147_at	ARSK	arylsulfatase family, member K	1.97592
239002_at	ASPM	asp (abnormal spindle) homolog, microcephaly associated	2.35391
		(Drosophila)
1554816_at	ASTN2	astrotactin 2	4.64925
233536_at	ASXL3	additional sex combs like 3 (Drosophila)	2.11586
1569729_a_at	ASZ1	ankyrin repeat, SAM and basic leucine zipper domain containing 1	1.59531
1559485_at	ATG2B	ATG2 autophagy related 2 homolog B (S. cerevisiae)	1.71224
228190_at	ATG4C ///	ATG4 autophagy related 4 homolog C (S. cerevisiae) /// Ctr9,	−1.50066
	CTR9	Paf1/RNA polymerase
220920_at	ATP10B	ATPase, class V, type 10B	1.91809
220556_at	ATP1B4	ATPase, (Na+)/K+ transporting, beta 4 polypeptide	1.63153
211137_s_at	ATP2C1	ATPase, Ca++ transporting, type 2C, member 1	−1.51541
214594_x_at	ATP8B1	ATPase, class I, type 8B, member 1	1.78628
216129_at	ATP9A	ATPase, class II, type 9A	1.98899
1560404_a_at	ATPBD4	ATP binding domain 4	1.5843
1569796_s_at	ATRNL1	attractin-like 1	2.48281
222969_at	B3GALT1	UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, polypeptide 1	1.97721
239144_at	B3GAT2	beta-1,3-glucuronyltransferase 2 (glucuronosyltransferase S)	2.24315
206233_at	B4GALT6	UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase,	1.51182
		polypeptide 6
222446_s_at	BACE2	beta-site APP-cleaving enzyme 2	−1.70556
207712_at	BAGE	B melanoma antigen	1.65959
1555605_x_at	BAGE	B melanoma antigen	1.7285
1555369_at	BAGE	B melanoma antigen	1.55591
1555603_at	BAGE	B melanoma antigen	2.17743
211568_at	BAI3	brain-specific angiogenesis inhibitor 3	1.99551
219688_at	BBS7	Bardet-Biedl syndrome 7	−1.8488
1555555_at	BBS9	Bardet-Biedl syndrome 9	1.67715
233464_at	BCL2L14	BCL2-like 14 (apoptosis facilitator)	1.59747
1560683_at	BCL8	B-cell CLL/lymphoma 8	1.76236
1560684_x_at	BCL8	B-cell CLL/lymphoma 8	1.85157
239367_at	BDNF	brain-derived neurotrophic factor	1.96176
232368_at	BET3L	BET3 like (S. cerevisiae)	1.85928
1569674_at	BHLHB9	Clone 23955 mRNA sequence	1.73214
1569289_at	BIVM	Full length insert cDNA clone YB21E09	1.62223
205431_s_at	BMP5	bone morphogenetic protein 5	2.03195
242579_at	BMPR1B	bone morphogenetic protein receptor, type IB	3.69028
235723_at	BNC2	basonuclin 2	1.76632
232103_at	BPNT1	3′(2′),5′-bisphosphate nucleotidase 1	−1.52974
206044_s_at	BRAF ///	v-raf murine sarcoma viral oncogene homolog B1 /// KIAA1549	1.58869
	KIAA1549
1569960_at	BRD7P3	bromodomain containing 7 pseudogene 3	3.05416
206787_at	BRDT	bromodomain, testis-specific	1.53605
207369_at	BRS3	bombesin-like receptor 3	2.10739
238966_at	BRUNOL4	bruno-like 4, RNA binding protein (Drosophila)	1.59417
230497_at	BRUNOL5	bruno-like 5, RNA binding protein (Drosophila)	1.81119
232416_at	BRUNOL5	bruno-like 5, RNA binding protein (Drosophila)	2.98452
202946_s_at	BTBD3	BTB (POZ) domain containing 3	−1.51798
207326_at	BTC	betacellulin	1.76063
234243_at	BXDC5	brix domain containing 5	3.97289
224667_x_at	C10orf104	chromosome 10 open reading frame 104	1.56473
1557548_at	C10orf108	chromosome 10 open reading frame 108	4.2936
1560851_at	C10orf136	chromosome 10 open reading frame 136	2.78294
244435_at	C10orf141	chromosome 10 open reading frame 141	1.90679
1556648_a_at	C10orf40	chromosome 10 open reading frame 40	2.61956
1557801_x_at	C11orf31	chromosome 11 open reading frame 31	−1.50635
1561985_at	C14orf39	chromosome 14 open reading frame 39	2.08706
224213_at	C14orf91	chromosome 14 open reading frame 91	1.51441
232507_at	C15orf41	chromosome 15 open reading frame 41	1.77387
208109_s_at	C15orf5	chromosome 15 open reading frame 5	1.62118
1560751_at	C18orf16	chromosome 18 open reading frame 16	3.41883
223977_s_at	C18orf2	chromosome 18 open reading frame 2	2.32467
244495_x_at	C18orf45	chromosome 18 open reading frame 45	1.64232
1553652_a_at	C18orf54	chromosome 18 open reading frame 54	1.96326
1556288_at	C18orf62	chromosome 18 open reading frame 62	2.60662
1552908_at	C1orf150	chromosome 1 open reading frame 150	2.85331
1554540_at	C1orf67	chromosome 1 open reading frame 67	1.74707
233598_at	C20orf187	chromosome 20 open reading frame 187	2.12033
1554657_a_at	C20orf26	chromosome	20 open reading frame 26	1.7578
232953_at	C20orf69 ///	chromosome 20 open reading frame 69 /// similar to hypothetical	1.62957
	DKFZP434B2016	protein LOC28470
	///
	LOC643670 ///
	LOC728105 ///
	LOC728323 ///
	PCMTD2
234314_at	C20orf74	chromosome 20 open reading frame 74	1.68
240068_at	C21orf130	chromosome 21 open reading frame 130	2.30653
1557481_a_at	C21orf131	chromosome 21 open reading frame 131	2.67119
239999_at	C21orf34	CDNA FLJ38295 fis, clone FCBBF3012332	1.71918
240801_at	C21orf37	chromosome 21 open reading frame 37	2.52149
1552876_at	C21orf89	chromosome 21 open reading frame 89	1.74874
244467_at	C22:CTA-	transmembrane protein 46-like	−1.50447
	250D10.9
1552979_at	C2orf52	chromosome 2 open reading frame 52	1.5065
1558519_at	C2orf67 /// RPE	Chromosome 2 open reading frame 67, mRNA (cDNA clone	1.54141
		MGC: 27010 IMAGE: 4829661) //
231081_at	C2orf73	chromosome 2 open reading frame 73	1.83581
241998_at	C2orf80	chromosome 2 open reading frame 80	2.15326
1554147_s_at	C3orf15	chromosome 3 open reading frame 15	1.5927
1554528_at	C3orf15	chromosome 3 open reading frame 15	2.15191
1555719_a_at	C3orf15	chromosome 3 open reading frame 15	2.82189
223990_at	C4orf17	chromosome 4 open reading frame 17	1.61603
231565_at	C4orf22	chromosome 4 open reading frame 22	1.55741
231612_at	C4orf35	chromosome 4 open reading frame 35	1.55132
1555096_at	C4orf37	chromosome 4 open reading frame 37	1.87794
1553106_at	C5orf24	chromosome 5 open reading frame 24	−1.84772
234457_at	C6orf12	chromosome 6 open reading frame 12	2.8135
1552575_a_at	C6orf141	chromosome 6 open reading frame 141	1.70056
232152_at	C6orf182 ///	chromosome 6 open reading frame 182 /// chromosome 6 open	2.19633
	C6orf182P	reading frame 182 pseu
244829_at	C6orf218	Chromosome 6 open reading frame 218 (C6orf218), mRNA	2.4961
211351_at	C6orf54	chromosome 6 open reading frame 54	2.04304
1566865_at	C7orf38	chromosome 7 open reading frame 38	1.98885
209446_s_at	C7orf44	chromosome 7 open reading frame 44	−1.51989
1553329_at	C7orf45	chromosome 7 open reading frame 45	2.3417
240626_at	C8orf15	chromosome 8 open reading frame 15	1.70317
231380_at	C8orf34	chromosome 8 open reading frame 34	1.78353
218541_s_at	C8orf4	chromosome 8 open reading frame 4	1.99089
214796_at	C8orf79	chromosome 8 open reading frame 79	1.71345
1560207_at	C8orf81	chromosome 8 open reading frame 81	3.37061
206727_at	C9	complement component 9	1.66942
230522_s_at	C9orf100	chromosome 9 open reading frame 100	−1.55527
1557541_at	C9orf122	chromosome 9 open reading frame 122	1.55302
208077_at	C9orf38	chromosome 9 open reading frame 38	2.77328
1558414_at	C9orf4	chromosome 9 open reading frame 4	1.61823
1560558_at	C9orf80	chromosome 9 open reading frame 80	3.13268
1556516_at	C9orf93	CDNA clone IMAGE: 5312512	2.11837
1553433_at	C9orf93	chromosome 9 open reading frame 93	2.37646
1557666_s_at	C9orf98	chromosome 9 open reading frame 98	1.57862
230976_at	C9orf98	chromosome 9 open reading frame 98	−1.65509
238636_at	CACNA1C	calcium channel, voltage-dependent, L type, alpha 1C subunit	1.73954
244256_at	CACNA1E	Voltage-operated calcium channel, alpha-1 subunit	2.70154
239884_at	CADPS	Ca++-dependent secretion activator	2.05688
219572_at	CADPS2	Ca++-dependent secretion activator 2	1.64739
201617_x_at	CALD1	caldesmon 1	2.15522
235834_at	CALD1	Caldesmon, 3′ UTR	1.76734
205525_at	CALD1	caldesmon 1	2.04665
1552421_a_at	CALR3	calreticulin 3	1.59981
212551_at	CAP2	CAP, adenylate cyclase-associated protein, 2 (yeast)	1.94441
1569450_at	CAPZA2	capping protein (actin filament) muscle Z-line, alpha 2	−1.55786
1553323_a_at	CATSPER2	cation channel, sperm associated 2	−1.76772
230981_at	CATSPER3	cation channel, sperm associated 3	−1.5308
1555920_at	CBX3	Heterochromatin protein HP1Hs-gamma	−1.65486
1553886_at	CCDC108	coiled-coil domain containing 108	2.91507
1561477_at	CCDC144A	coiled-coil domain containing 144A	3.37527
1561271_at	CCDC144C	coiled-coil domain containing 144C	3.46131
243565_at	CCDC150	coiled-coil domain containing 150	1.71562
237475_x_at	CCDC152	coiled-coil domain containing 152	1.54515
1553849_at	CCDC26	coiled-coil domain containing 26	1.9386
1553666_at	CCDC34	coiled-coil domain containing 34	1.8159
233259_at	CCDC48	PREDICTED: Homo sapiens similar to hCG20004	2.53391
		(LOC729581), mRNA
1558893_a_at	CCDC67	coiled-coil domain containing 67	1.69471
214710_s_at	CCNB1	cyclin B1	−1.54345
220351_at	CCRL1	chemokine (C-C motif) receptor-like 1	3.68023
229900_at	CD109	CD109 molecule	1.62542
215784_at	CD1E	CD1e molecule	2.06446
1552509_a_at	CD300LG	CD300 molecule-like famil member g	1.53768
1554519_at	CD80	CD80 molecule	−1.71348
241120_s_at	CDC20B	Cell division cycle 20 homolog B (S. cerevisiae), mRNA (cDNA	1.50701
		clone IMAGE: 5206729
240161_s_at	CDC20B	Cell division cycle 20 homolog B (S. cerevisiae), mRNA (cDNA	2.04212
		clone IMAGE: 5206729
1555772_a_at	CDC25A	cell division cycle 25 homolog A (S. pombe)	3.35221
232266_x_at	CDC2L5	CDNA FLJ35215 fis, clone PROST2000079, highly similar to	1.52631
		Homo sapiens mRNA for C
240735_at	CDC42BPA	Ser-thr protein kinase PK428	1.53612
220115_s_at	CDH10	cadherin	10, type 2 (T2-cadherin)	2.15879
236179_at	CDH11	cadherin 11, type 2, OB-cadherin (osteoblast)	1.70475
207149_at	CDH12	cadherin 12, type 2 (N-cadherin 2)	1.62637
206898_at	CDH19	cadherin 19, type 2	1.56233
220679_s_at	CDH7	cadherin 7, type 2	1.80801
241911_at	CDKL3	cyclin-dependent kinase-like 3	1.65132
204159_at	CDKN2C	cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)	−1.5149
228744_at	CEP27	centrosomal protein 27 kDa	−1.53605
229208_at	CEP27	centrosomal protein 27 kDa	−1.51058
241836_x_at	CEP97	centrosomal protein 97 kDa	1.50275
207874_s_at	CFHR4	complement factor H-related 4	1.74706
235117_at	CHAC2	ChaC, cation transport regulator homolog 2 (E. coli)	−1.8177
220619_at	CHD7	chromodomain helicase DNA binding protein 7	1.76809
1565951_s_at	CHML	choroideremia-like (Rab escort protein 2)	−1.91904
206079_at	CHML	choroideremia-like (Rab escort protein 2)	−1.64317
214596_at	CHRM3	cholinergic receptor, muscarinic 3	2.54248
211587_x_at	CHRNA3	cholinergic receptor, nicotinic, alpha 3	1.61917
221107_at	CHRNA9	cholinergic receptor, nicotinic, alpha 9	1.56409
220026_at	CLCA4	chloride channel regulator 4	2.16081
214598_at	CLDN8	claudin 8	1.81271
219414_at	CLSTN2	calsyntenin 2	1.84839
1552588_a_at	CNBD1	cyclic nucleotide binding domain containing 1	1.55712
1552344_s_at	CNOT7	CCR4-NOT transcription complex, subunit 7	−1.82468
239989_at	CNTLN	centlein, centrosomal protein	2.22761
227209_at	CNTN1	Contactin 2 precursor (CNTN1)	1.77739
229084_at	CNTN4	contactin 4	2.67917
207195_at	CNTN6	contactin 6	1.56557
205229_s_at	COCH	coagulation factor C homolog, cochlin (Limulus polyphemus)	−1.9015
205941_s_at	COL10A1	collagen, type X, alpha 1	1.7013
37892_at	COL11A1	collagen, type XI, alpha 1	2.34283
1556499_s_at	COL1A1	collagen, type I, alpha 1	4.18573
202403_s_at	COL1A2	collagen, type I, alpha 2	1.61064
229218_at	COL1A2	collagen, type I, alpha 2	4.15668
1555253_at	COL25A1	collagen, type XXV, alpha 1	3.31837
225293_at	COL27A1	collagen, type XXVII, alpha 1	1.80939
211161_s_at	COL3A1	collagen, type III, alpha 1	1.88084
215076_s_at	COL3A1	collagen, type III, alpha 1	1.84665
232458_at	COL3A1	MRNA 3′ region for pro-alpha1(III) collagen	2.19054
207420_at	COLEC10	collectin sub-family member 10 (C-type lectin)	1.54892
217645_at	COX16	COX16 cytochrome c oxidase assembly homolog (S. cerevisiae)	−1.59605
227253_at	CP	ceruloplasmin (ferroxidase)	1.66043
1552511_a_at	CPA6	carboxypeptidase A6	2.12705
227721_at	CPAMD8	C3 and PZP-like, alpha-2-macroglobulin domain containing 8	−2.00772
1555250_a_at	CPEB3	cytoplasmic polyadenylation element binding protein 3	1.57893
204920_at	CPS1	carbamoyl-phosphate synthetase 1, mitochondrial	1.95567
1552714_at	CREG2	cellular repressor of E1A-stimulated genes 2	2.09357
237502_at	CRLS1	Cardiolipin synthase 1 (CRLS1), transcript variant 2, mRNA	1.62771
1555958_at	CRTAC1	cartilage acidic protein 1	1.57641
1557143_at	CSMD2	CUB and Sushi multiple domains 2	1.65198
1553080_at	CSN1S2A	casein alpha s2-like A	1.73631
207030_s_at	CSRP2	cysteine and glycine-rich protein 2	1.92858
1567912_s_at	CT45-4 ///	cancer/testis antigen CT45-4 /// cancer/testis antigen CT45-6 ///	5.90054
	CT45-6 ///	hypothetical p
	LOC100133581
	/// RP13-36C9.1
	/// RP13-36C9.3
	/// RP13-36C9.6
	/// XX-
	FW88277B6.1
231568_at	CT47.7 ///	cancer/testis CT47 family, member 7 /// cancer/testis CT47	1.71304
	CT47.8 /// RP6-	family, member 8 ///
	166C19.1 ///
	RP6-166C19.10
	/// RP6-
	166C19.11 ///
	RP6-166C19.2
	/// RP6-
	166C19.3 ///
	RP6-166C19.4
	/// RP6-
	166C19.5 ///
	RP6-166C19.6
	/// RP6-
	166C19.9
213597_s_at	CTDSPL	CTD (carboxy-terminal domain, RNA polymerase II, polypeptide	1.93739
		A) small phosphatas
209617_s_at	CTNND2	catenin (cadherin-associated protein), delta 2 (neural plakophilin-	1.50335
		related arm-r
203917_at	CXADR	coxsackie virus and adenovirus receptor	2.66153
231389_at	CXorf41	chromosome X open reading frame 41	1.97677
1553466_at	CXorf59	chromosome X open reading frame 59	2.19023
235991_at	CYB5RL	cytochrome b5 reductase-like	−1.53055
216809_at	CYLC1	cylicin, basic protein of sperm head cytoskeleton 1	1.90782
207780_at	CYLC2	cylicin, basic protein of sperm head cytoskeleton 2	1.65232
240863_at	CYP19A1	cytochrome P450, family 19, subfamily A, polypeptide 1	2.21129
214235_at	CYP3A5	cytochrome P450, family 3, subfamily A, polypeptide 5	1.80203
205939_at	CYP3A7	cytochrome P450, family 3, subfamily A, polypeptide 7	1.70992
205472_s_at	DACH1	dachshund homolog 1 (Drosophila)	1.65928
239738_at	DACH2	dachshund homolog 2 (Drosophila)	1.51034
1562772_a_at	DAND5	DAN domain family, member 5	1.73689
238757_at	DBF4B	DBF4 homolog B (S. cerevisiae)	−1.67188
238508_at	DBF4B	DBF4 homolog B (S. cerevisiae)	−1.81109
205369_x_at	DBT	dihydrolipoamide branched chain transacylase E2	1.72887
213865_at	DCBLD2	discoidin, CUB and LCCL domain containing 2	1.55339
205399_at	DCLK1	doublecortin-like kinase 1	1.62886
215303_at	DCLK1	doublecortin-like kinase 1	3.56201
201893_x_at	DCN	decorin	1.94418
227561_at	DDR2	discoidin domain receptor tyrosine kinase 2	1.53865
223662_x_at	DDX59	DEAD (Asp-Glu-Ala-Asp) box polypeptide 59	1.55041
1553002_at	DEFB105A ///	defensin, beta 105A /// defensin, beta 105B	1.94929
	DEFB105B
1552411_at	DEFB106A ///	defensin, beta 106A /// defensin, beta 106B	1.9024
	DEFB106B
1563450_at	DEFB107A ///	defensin, beta 107A /// defensin, beta 107B	3.12379
	DEFB107B
1562167_a_at	DEFB122	defensin, beta 122 (pseudogene)	1.58206
207356_at	DEFB4	defensin, beta 4	1.95828
238917_s_at	DENND5B	DENN/MADD domain containing 5B	−1.87705
234071_at	DEPDC6	DEP domain containing 6	1.54924
216947_at	DES	desmin	4.20247
1553524_at	DGKB	diacylglycerol kinase, beta 90 kDa	2.81068
203699_s_at	DIO2	deiodinase, iodothyronine, type II	1.61583
1557633_at	DKFZp434K191	POM121 membrane glycoprotein-like 1 pseudogene	1.87034
1569476_at	DKFZP434L187	CDNA clone IMAGE: 5022014	3.78072
206819_at	DKFZP434P211	POM121 membrane glycoprotein-like 1 pseudogene	2.57115
222253_s_at	DKFZP434P211	POM121 membrane glycoprotein-like 1 pseudogene	5.5328
216877_at	DKFZp686O1327	EST clone 251800 mariner transposon Hsmar1 sequence	2.46877
224199_at	DKK2	dickkopf homolog 2 (Xenopus laevis)	1.52116
242631_x_at	DLC1	deleted in liver cancer 1	1.70843
233056_x_at	DLGAP4	discs, large (Drosophila) homolog-associated protein 4	1.52268
207147_at	DLX2	distal-less homeobox 2	2.38281
239309_at	DLX6	distal-less homeobox 6	4.54905
220493_at	DMRT1	doublesex and mab-3 related transcription factor 1	2.29697
237804_at	DNAH11	Axonemal dynein heavy chain (DNAH11), partial	1.71964
1560416_at	DNAH11	dynein, axonemal, heavy chain 11	2.87499
220725_x_at	DNAH3	Dynein, axonemal, heavy chain 3 (DNAH3), mRNA	1.58728
1552675_at	DNAJB7	DnaJ (Hsp40) homolog, subfamily B, member 7	1.69507
1558501_at	DNM3	dynamin 3	1.56409
214844_s_at	DOK5	docking portein 5	2.18827
207789_s_at	DPP6	dipeptidyl-peptidase 6	1.51336
231385_at	DPPA3 ///	developmental pluripotency associated 3 /// germ and embryonic	2.12291
	STELLAR	stem cell enriche
241199_x_at	DPPA4	developmental pluripotency associated 4	4.80564
1557290_at	DPY19L2 ///	dpy-19-like 2 (C. elegans) /// dpy-19-like 2 pseudogene 1 (C. elegans)	1.62779
	DPY19L2P1 ///	/// dpy-1
	DPY19L2P2 ///
	DPY19L2P4
240218_at	DSCAM	Down syndrome cell adhesion molecule	1.59287
1552708_a_at	DUSP19	dual specificity phosphatase 19	2.25968
204014_at	DUSP4	dual specificity phosphatase 4	1.67536
1569843_at	DYNC1I1	dynein, cytoplasmic 1, intermediate chain 1	1.78891
1565149_at	DYNC2H1	dynein, cytoplasmic 2, heavy chain 1	2.12554
204271_s_at	EDNRB	endothelin receptor type B	1.68002
1558300_at	EFCAB5	EF-hand calcium binding domain 5	2.24756
233814_at	EFNA5	Receptor tyrosine kinase ligand LERK-7 precursor (EPLG7)	1.57917
219454_at	EGFL6	EGF-like-domain, multiple 6	1.63159
1565483_at	EGFR	epidermal growth factor receptor (erythroblastic leukemia viral	1.75454
		(v-erb-b) oncoge
219850_s_at	EHF	ets homologous factor	2.15949
232360_at	EHF	ets homologous factor	2.97474
208427_s_at	ELAVL2	ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2	1.52696
		(Hu antigen B)
228260_at	ELAVL2	ELAV (embryonic lethal, abnormal vision, Drosophila)-like 2	4.26399
		(Hu antigen B)
227612_at	ELAVL3	ELAV (embryonic lethal, abnormal vision, Drosophila)-like 3	6.80428
		(Hu antigen C)
238073_at	ELAVL4	ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4	1.54026
		(Hu antigen D)
229581_at	ELFN1	extracellular leucine-rich repeat and fibronectin type III domain	1.84175
		containing 1
1565254_s_at	ELL	elongation factor RNA polymerase II	2.51255
1557836_at	ELMOD2	ELMO/CED-12 domain containing 2 (ELMOD2), mRNA	1.86018
219134_at	ELTD1	EGF, latrophilin and seven transmembrane domain containing 1	2.15765
219436_s_at	EMCN	endomucin	1.94422
1553672_at	ENAH	enabled homolog (Drosophila)	1.64531
205066_s_at	ENPP1	ectonucleotide pyrophosphatase/phosphodiesterase 1	1.63382
205065_at	ENPP1	ectonucleotide pyrophosphatase/phosphodiesterase 1	1.52899
229292_at	EPB41L5	erythrocyte membrane protein band 4.1 like 5	−1.50762
206070_s_at	EPHA3	EPH receptor A3	2.33775
211164_at	EPHA3	EPH receptor A3	4.39517
216837_at	EPHA5	EPH receptor A5	3.21486
229288_at	EPHA7	EPH receptor A7	1.56981
216999_at	EPOR	erythropoietin receptor	2.17646
202454_s_at	ERBB3	v-erb-b2 erythroblastic leukemia viral oncogene homolog 3	1.58154
		(avian)
206794_at	ERBB4	v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)	1.84155
233498_at	ERBB4	v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)	1.68382
214053_at	ERBB4	v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)	3.22256
216440_at	ERC1	RAB6 interacting protein 2, mRNA (cDNA clone	2.35068
		IMAGE: 4343516)
1569583_at	EREG	epiregulin	1.55022
213365_at	ERI2	exoribonuclease 2	−1.60968
1564473_at	ESCO2	Clone 305-4G mRNA sequence	1.51202
235588_at	ESCO2	establishment of cohesion 1 homolog 2 (S. cerevisiae)	2.61641
209966_x_at	ESRRG	estrogen-related receptor gamma	1.74023
224454_at	ETNK1	ethanolamine kinase	1	1.50058
206501_x_at	ETV1	ets variant 1	1.64042
230102_at	ETV5	Ets-related protein	1.68286
243277_x_at	EVI1	ecotropic viral integration site 1	2.35623
208298_at	EVI5	ecotropic viral integration site 5	2.18273
207327_at	EYA4	eyes absent homolog 4 (Drosophila)	2.48321
1569592_a_at	F11	coagulation factor XI	2.291
220575_at	FAM106A	family with sequence similarity 106, member A	1.54075
209074_s_at	FAM107A	family with sequence similarity 107, member A	1.63185
1557129_a_at	FAM111B	family with sequence similarity 111, member B	2.02161
212979_s_at	FAM115A	family with sequence similarity 115, member A	1.61927
1555944_at	FAM120A	family with sequence similarity 120A	−1.5885
1552323_s_at	FAM122C	family with sequence similarity 122C	−1.54021
1553720_a_at	FAM123A	family with sequence similarity 123A	1.51994
235465_at	FAM123A	family with sequence similarity 123A	1.86652
230496_at	FAM123A	family with sequence similarity 123A	2.50999
231396_s_at	FAM126A	family with sequence similarity 126, member A	−1.50922
223625_at	FAM126A	family with sequence similarity 126, member A	−1.81004
239481_at	FAM133A	family with sequence similarity 133, member A	4.33493
1569025_s_at	FAM13A1	family with sequence similarity 13, member A1	1.57074
222291_at	FAM149A	family with sequence similarity 149, member A	2.00081
214825_at	FAM155A	family with sequence similarity 155, member A	1.68899
230869_at	FAM155A	family with sequence similarity 155, member A	4.25508
242687_at	FAM160A1	family with sequence similarity 160, member A1	1.63033
213304_at	FAM179B	family with sequence similarity 179, member B	−1.60915
230539_at	FAM182A	family with sequence similarity 182, member A	1.57619
216053_x_at	FAM182A	CDNA FLJ38374 fis, clone FEBRA2002552	1.70561
222205_x_at	FAM182B ///	family with sequence similarity 182, member B /// hypothetical	2.46888
	RP13-401N8.2	gene supported by
234945_at	FAM54A	family with sequence similarity 54, member A	2.36602
234331_s_at	FAM84A	family with sequence similarity 84, member A	1.85031
1555538_s_at	FAM9B	family with sequence similarity 9, member B	1.61504
1568889_at	FANCD2	Fanconi anemia, complementation group D2	1.62037
1568891_x_at	FANCD2	Fanconi anemia, complementation group D2	2.51522
239246_at	FARP1	CDEP	1.90491
201579_at	FAT1	FAT tumor suppressor homolog 1 (Drosophila)	2.29159
1558964_at	FAT3	FAT tumor suppressor homolog 3 (Drosophila)	1.55077
1560490_at	FAT3	FAT tumor suppressor homolog 3 (Drosophila)	1.79133
236029_at	FAT3	FAT tumor suppressor homolog 3 (Drosophila)	4.17669
233087_at	FBXL17	F-box and leucine-rich repeat protein 17	1.83402
218875_s_at	FBXO5	F-box protein 5	−1.6348
224402_s_at	FCRL4	Fc receptor-like 4	1.66601
224403_at	FCRL4	Fc receptor-like 4	3.64968
1555136_at	FGD6	FYVE, RhoGEF and PH domain containing 6	2.22566
214589_at	FGF12	fibroblast growth factor 12	1.87587
231523_at	FGF14	fibroblast growth factor 14	2.00116
214284_s_at	FGF18	Fibroblast growth factor 18, mRNA (cDNA clone IMAGE: 10529	1.54076
		IMAGE: 3948893)
220394_at	FGF20	fibroblast growth factor 20	1.85663
210311_at	FGF5	fibroblast growth factor 5	1.59913
205782_at	FGF7	fibroblast growth factor 7 (keratinocyte growth factor)	1.67479
239710_at	FIGN	fidgetin	4.1857
238964_at	FIGN	fidgetin	2.65603
1556325_at	FILIP1	filamin A interacting protein 1	2.16122
1570515_a_at	FILIP1	filamin A interacting protein 1	1.86592
223667_at	FKBP7	FK506 binding protein 7	1.51179
220828_s_at	FLJ11292	hypothetical protein FLJ11292	1.81486
215187_at	FLJ11292	hypothetical protein FLJ11292	2.15766
1564160_at	FLJ16686	FLJ16686 protein	1.79597
234830_at	FLJ20518	similar to FSHD region gene 2 protein	2.17839
221172_at	FLJ21075	hypothetical protein FLJ21075	1.7343
233604_at	FLJ22763	hypothetical gene supported by AK026416	2.69416
217016_x_at	FLJ23172 ///	hypothetical LOC389177 /// transmembrane protein 212	1.7451
	TMEM212
1553614_a_at	FLJ25694	hypothetical protein FLJ25694	1.723
241953_at	FLJ25694 ///	hypothetical protein FLJ25694 /// keratin associated protein 21-1	1.67966
	KRTAP21-1
1557155_a_at	FLJ30375	CDNA clone IMAGE: 5301781	2.6058
241440_at	FLJ30375	hypothetical gene supported by AK054937	2.70383
236739_at	FLJ30594	CDNA FLJ34044 fis, clone FCBBF2007080	3.41974
1553775_at	FLJ31715	hypothetical protein FLJ31715	−1.57858
1553354_a_at	FLJ31958	hypothetical protein FLJ31958	1.71642
230047_at	FLJ32810	hypothetical protein FLJ32810	1.76353
1553472_at	FLJ32955	hypothetical protein FLJ32955	2.65054
1569378_at	FLJ33297	CDNA FLJ33297 fis, clone BNGH42001406	1.76909
1553335_x_at	FLJ34047	hypothetical protein FLJ34047	1.59989
1559277_at	FLJ35700	hypothetical protein FLJ35700	1.66616
1557206_at	FLJ35848	hypothetical protein FLJ35848	2.97097
1566480_x_at	FLJ35848	Hypothetical protein FLJ35848, mRNA (cDNA clone	2.19166
		IMAGE: 5402642)
1557895_at	FLJ35934	FLJ35934 protein	2.05515
1561171_a_at	FLJ36131 ///	hypothetical protein FLJ36131 /// hypothetical protein	1.78937
	LOC100131452	LOC100131452 /// transmem
	///
	LOC100132025
	///
	LOC100132566
	///
	LOC100132727
	/// LOC729272
1560790_at	FLJ36144	hypothetical protein FLJ36144	2.06719
1556558_s_at	FLJ36665	hypothetical protein FLJ36665	−1.73079
231527_at	FLJ36840	CDNA FLJ36840 fis, clone ASTRO2011461	1.66566
1558579_at	FLJ37786	hypothetical LOC642691	2.45337
242683_at	FLJ38028	hypothetical gene supported by AK095347	1.51579
242546_at	FLJ39632	hypothetical LOC642477	2.20629
239010_at	FLJ39632	CDNA clone IMAGE: 5270501	2.23008
231882_at	FLJ39632 ///	hypothetical LOC642477 /// similar to double homeobox A	2.09022
	LOC100131139
1566665_at	FLJ40176	hypothetical LOC121951	1.68357
1568698_at	FLJ43080	hypothetical protein LOC642987	2.07737
1565786_x_at	FLJ45482	hypothetical LOC645566	1.60292
240259_at	FLRT2	CDNA FLJ51243 complete cds, highly similar to Leucine-rich	2.20213
		repeat transmembrane
219250_s_at	FLRT3	fibronectin leucine rich transmembrane protein 3	1.59215
1559244_at	FMN2	formin 2	2.22149
223618_at	FMN2	formin 2	1.85606
231231_at	FMNL3	KIAA2014 protein	2.66876
226930_at	FNDC1	fibronectin type III domain containing 1	1.78354
217483_at	FOLH1	folate hydrolase (prostate-specific membrane antigen) 1	2.41619
217487_x_at	FOLH1	folate hydrolase (prostate-specific membrane antigen) 1	4.54562
40284_at	FOXA2	forkhead box A2	3.21218
1553613_s_at	FOXC1	forkhead box C1	1.8881
206018_at	FOXG1	forkhead box G1	1.85819
235201_at	FOXP2	forkhead box P2	2.75837
1555352_at	FOXP2	forkhead box P2	1.7166
230964_at	FREM2	FRAS1 related extracellular matrix protein 2	4.03728
243689_s_at	FRG1B	Hypothetical protein LOC283788, mRNA (cDNA clone	2.17705
		MGC: 23868 IMAGE: 4297267)
234949_at	FRG1B	Hypothetical protein LOC283788, mRNA (cDNA clone	2.27959
		MGC: 23868 IMAGE: 4297267)
207178_s_at	FRK	fyn-related kinase	1.87638
1570207_at	FRRS1	ferric-chelate reductase 1	2.89483
1562625_at	FRYL	FRY-like	1.99342
244419_at	FRZB	Fritz	1.54036
230904_at	FSD1L	fibronectin type III and SPRY domain containing 1-like	−1.99072
223985_at	FSD1L	fibronectin type III and SPRY domain containing 1-like	1.83509
207345_at	FST	follistatin	2.76648
203705_s_at	FZD7	frizzled homolog 7 (Drosophila)	1.55517
1553024_at	G30	protein LG30-like	2.51805
222187_x_at	G3BP1	GTPase activating protein (SH3 domain) binding protein 1	1.62305
206952_at	G6PC	glucose-6-phosphatase, catalytic subunit	2.12833
238569_at	GABBR1	GABA-BR1a (hGB1a) receptor	−1.61754
209990_s_at	GABBR2	gamma-aminobutyric acid (GABA) B receptor, 2	1.59875
233437_at	GABRA4	gamma-aminobutyric acid (GABA) A receptor, alpha 4	3.25934
207010_at	GABRB1	gamma-aminobutyric acid (GABA) A receptor, beta 1	2.42007
242344_at	GABRB2	gamma-aminobutyric acid (GABA) A receptor, beta 2	5.10676
1557122_s_at	GABRB2	gamma-aminobutyric acid (GABA) A receptor, beta 2	8.54122
229724_at	GABRB3	gamma-aminobutyric acid (GABA) A receptor, beta 3	1.55943
1563533_at	GADL1	glutamate decarboxylase-like 1	4.0883
208283_at	GAGE1	G antigen 1	2.39924
207739_s_at	GAGE1 ///	G antigen 1 /// G antigen 12F /// G antigen 12G /// G antigen 12I	2.7548
	GAGE12F ///	/// G antigen
	GAGE12G ///
	GAGE12I ///
	GAGE12J ///
	GAGE2A ///
	GAGE2B ///
	GAGE2C ///
	GAGE2D ///
	GAGE2E ///
	GAGE3 ///
	GAGE4 ///
	GAGE5 ///
	GAGE6 ///
	GAGE7 ///
	GAGE8
237183_at	GALNT5	CDNA FLJ75131 complete cds, highly similar to Homo sapiens	1.57858
		UDP-N-acetyl-alpha-D-
240390_at	GALNT5	UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-	4.19183
		acetylgalactosaminyltransferase
236361_at	GALNTL2	UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-	1.9112
		acetylgalactosaminyltransferase
220124_at	GAN	gigaxonin	1.78227
204471_at	GAP43	growth associated protein 43	1.67109
219954_s_at	GBA3	glucosidase, beta, acid 3 (cytosolic)	1.56599
230788_at	GCNT2	glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (1	−1.71043
		blood group)
236548_at	GIPC2	GIPC PDZ domain containing family, member 2	2.02931
230258_at	GLIS3	GLIS family zinc finger 3	2.8996
244680_at	GLRB	glycine receptor, beta	1.90493
235371_at	GLT8D4	glycosyltransferase 8 domain containing 4	1.5501
1554712_a_at	GLYATL2	glycine-N-acyltransferase-like 2	2.06041
204763_s_at	GNAO1	guanine nucleotide binding protein (G protein), alpha activating	2.09098
		activity polype
229274_at	GNAS	Adenyl cyclase mRNA	−1.62372
207166_at	GNGT1	guanine nucleotide binding protein (G protein), gamma	1.92988
		transducing activity polyp
204324_s_at	GOLIM4	golgi integral membrane protein 4	1.65786
1555199_at	GOSR1	golgi SNAP receptor complex member 1	3.06916
1553879_a_at	GOT1L1	glutamic-oxaloacetic transaminase 1-like 1	1.59882
1553878_at	GOT1L1	glutamic-oxaloacetic transaminase 1-like 1	1.95653
215554_at	GPLD1	glycosylphosphatidylinositol specific phospholipase D1	1.54336
236024_at	GPM6A	glycoprotein M6A	2.04441
212950_at	GPR116	G protein-coupled receptor 116	1.52524
212951_at	GPR116	G protein-coupled receptor 116	1.57258
1555122_at	GPR125	G protein-coupled receptor 125	2.42496
233887_at	GPR126	G protein-coupled receptor 126	1.58837
1553025_at	GPR126	G protein-coupled receptor 126	1.68374
209631_s_at	GPR37	G protein-coupled receptor 37 (endothelin receptor type B-like)	1.56859
219898_at	GPR85	G protein-coupled receptor 85	2.09828
238049_at	GRAMD3	GRAM domain containing 3	2.61185
206204_at	GRB14	growth factor receptor-bound protein 14	2.23024
235504_at	GREM2	gremlin 2, cysteine knot superfamily, homolog (Xenopus laevis)	1.50319
219388_at	GRHL2	grainyhead-like 2 (Drosophila)	2.33499
205358_at	GRIA2	glutamate receptor, ionotropic, AMPA 2	2.02789
206730_at	GRIA3	glutamate receptor, ionotrophic, AMPA 3	2.12652
213845_at	GRIK2	glutamate receptor, ionotrophic, kainate 2	1.74884
205814_at	GRM3	glutamate receptor, metabotropic 3	2.30621
207235_s_at	GRM5	glutamate receptor, metabotropic 5	2.95593
207548_at	GRM7	glutamate receptor, metabotropic 7	1.64049
216992_s_at	GRM8	glutamate receptor, metabotropic 8	1.54515
235387_at	GSTCD	glutathione S-transferase, C-terminal domain containing	−1.51561
242656_at	GTF2H1	General transcription factor IIH, polypeptide 1, 62 kDa	−1.65352
		(GTF2H1), transcript vari
204237_at	GULP1	GULP, engulfment adaptor PTB domain containing 1	1.726
204235_s_at	GULP1	GULP, engulfment adaptor PTB domain containing 1	1.67838
215695_s_at	GYG2	glycogenin 2	1.67125
1559520_at	GYPA	Glycophorin A	3.86167
205523_at	HAPLN1	hyaluronan and proteoglycan link protein 1	1.50177
230895_at	HAPLN1	hyaluronan and proteoglycan link protein 1	2.33681
232848_at	hCG_1795283	hCG1818123	1.60873
232239_at	hCG_2024094	hCG2024094	−1.88082
216229_x_at	HCG2P7	HLA complex group 2 pseudogene 7	1.77053
1556351_at	HCN1	hyperpolarization activated cyclic nucleotide-gated potassium	2.3437
		channel 1
232414_at	HEATR1	HEAT repeat containing 1	1.52452
210331_at	HECW1	HECT, C2 and WW domain containing E3 ubiquitin protein	1.90413
		ligase 1
233075_at	HERC2P7	hect domain and RLD 2 pseudogene 7	1.58465
1555318_at	HIF3A	hypoxia inducible factor 3, alpha subunit	2.41676
216548_x_at	HMG4L	high-mobility group (nonhistone chromosomal) protein 4-like	1.68308
228772_at	HNMT	histamine N-methyltransferase	−1.93357
217353_at	HNRNPA1 ///	heterogeneous nuclear ribonucleoprotein A1 /// heterogeneous	1.6011
	HNRNPA1L2	nuclear ribonucleop
	/// HNRPA1L-2
	/// HNRPA1P5
	///
	LOC100128836
	/// LOC120364
	/// LOC391670
	/// LOC402112
	/// LOC440125
	/// LOC642817
	/// LOC643033
	/// LOC644037
	/// LOC645001
	/// LOC728170
	/// LOC728643
	/// LOC728732
	/// LOC729102
	/// LOC729366
	/// LOC730246
227566_at	HNT	neurotrimin	2.73516
213793_s_at	HOMER1	homer homolog 1 (Drosophila)	1.91311
1566140_at	HOPX	HOP homeobox	1.73184
218959_at	HOXC10	homeobox C10	1.72818
206858_s_at	HOXC4 ///	homeobox C4 /// homeobox C6	2.37146
	HOXC6
229400_at	HOXD10	homeobox D10	2.16969
219985_at	HS3ST3A1	heparan sulfate (glucosamine) 3-O-sulfotransferase 3A1	1.65808
232276_at	HS6ST3	heparan sulfate 6-O-sulfotransferase 3	2.29584
206639_at	HTN1	histatin	1	1.56385
206786_at	HTN3	histatin 3	2.99589
207577_at	HTR4	5-hydroxytryptamine (serotonin) receptor 4	1.55186
211740_at	ICA1	islet cell autoantigen 1, 69 kDa	2.1923
213450_s_at	ICOSLG	inducible T-cell co-stimulator ligand	−1.56491
209291_at	ID4	inhibitor of DNA binding 4, dominant negative helix-loop-helix	2.00627
		protein
236478_at	IFNAR1	Interferon (alpha, beta and omega) receptor 1, mRNA (cDNA	−1.50715
		clone IMAGE: 4391580)
209540_at	IGF1	insulin-like growth factor 1 (somatomedin C)	2.21842
211959_at	IGFBP5	insulin-like growth factor binding protein 5	1.8742
214973_x_at	IGHD	immunoglobulin heavy constant delta	−1.81338
220567_at	IKZF2	IKAROS family zinc finger 2 (Helios)	1.53299
205992_s_at	IL15	interleukin	15	−1.73897
220663_at	IL1RAPL1	interleukin 1 receptor accessory protein-like 1	2.89062
222698_s_at	IMPACT	Impact homolog (mouse)	−1.54815
222250_s_at	INTS7	integrator complex subunit 7	−1.53873
228946_at	INTU	inturned planar cell polarity effector homolog (Drosophila)	1.66051
1557770_at	IPO11	importin 11	2.19277
241834_at	IPW	imprinted in Prader-Willi syndrome (non-protein coding)	2.05282
229538_s_at	IQGAP3	IQ motif containing GTPase activating protein 3	2.32378
1553949_at	IQSEC3	IQ motif and Sec7 domain 3	1.82434
242694_at	IQSEC3 ///	IQ motif and Sec7 domain 3 /// similar to IQ motif and Sec7	2.81166
	LOC100134209	domain-containing pr
	/// LOC731035
1568924_a_at	IQUB	IQ motif and ubiquitin domain containing	2.23724
206104_at	ISL1	ISL LIM homeobox 1	2.04554
242982_x_at	ITGB8	integrin, beta 8	1.72645
1557080_s_at	ITGBL1	integrin, beta-like 1 (with EGF-like repeat domains)	1.58327
214927_at	ITGBL1	integrin, beta-like 1 (with EGF-like repeat domains)	2.53432
242788_at	JMJD2D	jumonji domain containing 2D	1.7149
216763_at	KANK1	KN motif and ankyrin repeat domains 1, mRNA (cDNA clone	1.90238
		MGC: 43128 IMAGE: 5261060)
229125_at	KANK4	KN motif and ankyrin repeat domains 4	2.24666
1555673_at	KAP2.1B ///	keratin associated protein 2.1B /// keratin associated protein 2-4	1.99107
	KRTAP2-4 ///	/// hypotheti
	LOC644350 ///
	LOC728285 ///
	LOC728934 ///
	LOC730755
208123_at	KCNB2	potassium voltage-gated channel, Shab-related subfamily,	2.26862
		member 2
1555074_a_at	KCNH5	potassium voltage-gated channel, subfamily H (eag-related),	2.34582
		member 5
240591_at	KCNIP4	CDNA FLJ59677 complete cds, highly similar to Kv channel-	1.77751
		interacting protein 4
210179_at	KCNJ13	potassium inwardly-rectifying channel, subfamily J, member 13	1.61478
219564_at	KCNJ16	potassium inwardly-rectifying channel, subfamily J, member 16	2.4536
208404_x_at	KCNJ5	potassium inwardly-rectifying channel, subfamily J, member 5	1.52838
244455_at	KCNT2	potassium channel, subfamily T, member 2	1.96504
222664_at	KCTD15	potassium channel tetramerisation domain containing 15	−1.52793
222668_at	KCTD15	potassium channel tetramerisation domain containing 15	−1.53961
209781_s_at	KHDRBS3	KH domain containing, RNA binding, signal transduction	1.64262
		associated 3
207161_at	KIAA0087	KIAA0087	1.89736
227231_at	KIAA1211	KIAA1211 protein	1.60476
232762_at	KIAA1217	KIAA1217	1.727
235956_at	KIAA1377	KIAA1377	1.59988
233977_at	KIAA1772	KIAA1772	1.50426
236518_at	KIAA1984	KIAA1984	−1.58518
244427_at	KIF23	Mitotic kinesin-like protein-1 (MKLP-1 gene)	2.12055
220652_at	KIF24	kinesin family member 24	1.59148
234307_s_at	KIF26A	kinesin family member 26A	−1.73607
220657_at	KLHL11	kelch-like 11 (Drosophila)	−1.60971
210634_at	KLHL20	kelch-like 20 (Drosophila)	−1.58643
1553873_at	KLHL34	kelch-like 34 (Drosophila)	1.61075
211138_s_at	KMO	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	−1.69994
205306_x_at	KMO	kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)	−1.72294
243998_at	KRT222P	keratin 222 pseudogene	1.64083
210662_at	KYNU	kynureninase (L-kynurenine hydrolase)	−2.0753
1552490_at	LACE1	lactation elevated 1	1.753
215516_at	LAMB4	laminin, beta 4	2.22608
229953_x_at	LCA5	Leber congenital amaurosis 5	1.5775
213371_at	LDB3	LIM domain binding 3	4.85498
207409_at	LECT2	leukocyte cell-derived chemotaxin 2	3.74939
207092_at	LEP	leptin	1.65443
236761_at	LHFPL3	lipoma HMGIC fusion partner-like 3	1.57304
206140_at	LHX2	LIM homeobox 2	3.42338
225571_at	LIFR	leukemia inhibitory factor receptor alpha	2.72636
212328_at	LIMCH1	LIM and calponin homology domains 1	1.8332
212327_at	LIMCH1	LIM and calponin homology domains 1	2.30917
212325_at	LIMCH1	LIM and calponin homology domains 1	1.61665
232457_at	LIMCH1	LIM and calponin homology domains 1, mRNA (cDNA clone	1.61154
		MGC: 16598 IMAGE: 4110496)
219823_at	LIN28	lin-28 homolog (C. elegans)	1.63702
229349_at	LIN28B	lin-28 homolog B (C. elegans)	2.03446
241957_x_at	LIN7B	lin-7 homolog B (C. elegans)	−1.54121
219181_at	LIPG	lipase, endothelial	1.55778
242178_at	LIPI	lipase, member I	1.97767
216543_at	LOC100093698	unknown transcript	1.53623
217655_at	LOC100127972	hypothetical LOC100127972	−1.67943
224095_at	LOC100128175	similar to PRO2591	1.71793
207478_at	LOC100128329	similar to PRO2958	1.77096
229999_at	LOC100128416	Full length insert cDNA clone ZE12A08	−1.51964
215590_x_at	LOC100128640	PREDICTED: Homo sapiens hypothetical protein	1.71347
		LOC100128640 (LOC100128640), mRNA
240395_at	LOC100128727	hypothetical LOC100128727	1.50691
244723_at	LOC100129488	hypothetical protein LOC100129488	4.89676
244518_at	LOC100130452	similar to hCG1777700	1.67252
1560425_s_at	LOC100130868	hypothetical protein LOC100130868	1.784
215301_at	LOC100130958	hypothetical protein LOC100130958	2.02489
1565814_at	LOC100131040	hypothetical protein LOC100131040 /// tripartite motif-	1.71106
	/// TRIM36	containing 36
211341_at	LOC100131317	similar to hCG1781072 /// POU class 4 homeobox 1	1.57041
	/// POU4F1
237711_at	LOC100131980	similar to zinc finger protein 705A /// zinc finger protein 705G-	1.78011
	/// ZNF705G	like
1561170_at	LOC100132025	transmembrane domain-containing protein ENSP00000320207-	2.28603
		like
236181_at	LOC100132181	PREDICTED: Homo sapiens hypothetical protein	2.60614
		LOC100132181 (LOC100132181), mRNA
243336_at	LOC100132726	hypothetical protein LOC100132726	−1.55162
1558640_a_at	LOC100132788	MRNA (fetal brain cDNA e2_2g)	3.6619
241821_at	LOC100132894	hypothetical protein LOC100132894	3.24026
227631_at	LOC100133283	PREDICTED: Homo sapiens hypothetical protein	1.58351
		LOC100133283 (LOC100133283), mRNA
224110_at	LOC100133319	PRO1804	1.87425
1562974_at	LOC100133899	hypothetical protein LOC100133899	1.8921
1556704_s_at	LOC100133920	hypothetical protein LOC100133920 /// hypothetical protein	2.36676
	/// LOC286297	LOC286297
1557617_at	LOC100189589	hypothetical LOC100189589	2.06679
229994_at	LOC100190890	MRNA; cDNA DKFZp686J23256 (from clone	2.00185
		DKFZp686J23256)
234493_at	LOC116437	hypothetical protein LOC116437	1.59059
242469_at	LOC120376	Uncharacterized protein LOC120376 (LOC120376), mRNA	1.77817
1555988_a_at	LOC126536	hypothetical protein LOC126536	2.167
229178_at	LOC145786	hypothetical protein LOC145786	1.58445
229073_at	LOC145786	CDNA FLJ13221 fis, clone NT2RP4002075	3.33323
232450_at	LOC149351	hypothetical protein LOC149351	1.85318
1561343_a_at	LOC150005	hypothetical protein LOC150005	1.86593
239965_at	LOC151878	hypothetical protein LOC151878	2.92204
215978_x_at	LOC152719	hypothetical protein LOC152719	1.56227
239691_at	LOC196415	hypothetical protein LOC196415	1.53729
232370_at	LOC254057	hypothetical protein LOC254057	1.6305
1562501_at	LOC255177	hypothetical protein LOC255177	1.66618
1562527_at	LOC283027	hypothetical protein LOC283027	5.38799
1563854_s_at	LOC283045	hypothetical protein LOC283045	1.50235
1558195_at	LOC283404	hypothetical protein LOC283404	2.28078
1556425_a_at	LOC284219	hypothetical protein LOC284219	2.26468
214162_at	LOC284244	hypothetical protein LOC284244	3.07805
1563009_at	LOC284930	Homo sapiens, clone IMAGE: 5538478, mRNA	1.86884
1557267_s_at	LOC284952	hypothetical protein LOC284952	1.61866
1557570_a_at	LOC285084	hypothetical protein LOC285084	2.38931
1558601_at	LOC285194	hypothetical LOC285194	1.54813
1556528_at	LOC285326	hypothetical protein LOC285326	1.57263
1561096_at	LOC285419	hypothetical protein LOC285419	1.77787
1557107_at	LOC286002	hypothetical protein LOC286002	1.88346
1556573_s_at	LOC286178	hypothetical protein LOC286178	1.76489
1556421_at	LOC286189	hypothetical protein LOC286189	2.18301
240545_at	LOC286382	hypothetical protein LOC286382	1.91794
1557717_at	LOC338862	hypothetical protein LOC338862	3.97958
1557534_at	LOC339862	hypothetical protein LOC339862	1.51746
1560823_at	LOC340017	hypothetical protein LOC340017	2.06515
1563589_at	LOC340184	hypothetical protein LOC340184	1.9
1557664_at	LOC340239	PREDICTED: Homo sapiens hypothetical protein LOC340239,	1.67247
		transcript variant 2 (LO
1559002_at	LOC340544	hypothetical protein LOC340544	−1.5369
235606_at	LOC344595	hypothetical LOC344595	5.65601
1563022_at	LOC347475	UPF0625 coiled-coil domain-containing protein	2.7715
		ENSP00000359845
1558423_at	LOC349114	Homo sapiens, clone IMAGE: 4385460, mRNA	1.6894
233879_at	LOC374491	TPTE and PTEN homologous inositol lipid phosphatase	2.23513
		pseudogene
1558982_at	LOC375010	hypothetical LOC375010	2.62407
1558425_x_at	LOC388312 ///	hypothetical LOC388312 /// hypothetical LOC728417 ///	1.50876
	LOC728417 ///	hypothetical LOC729737 ///
	LOC729737 ///
	LOC730235
1560773_at	LOC388458	hypothetical gene supported by BC040718	1.99159
1560119_at	LOC389634	hypothetical LOC389634	1.56826
226582_at	LOC400043	hypothetical gene supported by BC009385	1.76427
1561414_at	LOC401497	similar to PRO2738	2.43388
1561997_at	LOC440061	PREDICTED: Homo sapiens misc RNA (LOC440061),	1.61784
		miscRNA
240268_at	LOC440117	hypothetical gene supported by BC037858	1.82436
214984_at	LOC440345	hypothetical protein LOC440345	4.24873
244766_at	LOC440354 ///	PI-3-kinase-related kinase SMG-1 pseudogene /// PI-3-kinase-	1.64874
	LOC595101 ///	related kinase SMG-1
	LOC641298 ///
	LOC728423 ///
	LOC729513 ///
	SMG1
216193_at	LOC440366	heet domain and RLD 2 pseudogene	1.81363
1562558_at	LOC440704	hypothetical gene supported by BC042042	2.40362
224426_s_at	LOC440888	ARP3 actin-related protein 3 homolog B pseudogene	3.36427
224424_x_at	LOC440888	ARP3 actin-related protein 3 homolog B pseudogene	2.83853
224425_x_at	LOC440888	ARP3 actin-related protein 3 homolog B pseudogene	3.33132
229095_s_at	LOC440895	LIM and senescent cell antigen-like domains 3-like	2.24538
222207_x_at	LOC441258	CDNA: FLJ20949 fis, clone ADSE01902	1.70745
220771_at	LOC51152	melanoma antigen	2.14963
220893_at	LOC57399	uncharacterized gastric protein ZA52P	1.76081
1559459_at	LOC613266	hypothetical LOC613266	−2.71264
1561098_at	LOC641365	hypothetical protein LOC641365	1.59224
1562223_at	LOC642426	hypothetical LOC642426	2.36874
1554996_at	LOC643955 ///	zinc finger protein 479 pseudogene /// zinc finger protein 479 ///	3.79321
	ZNF479 ///	zinc finger p
	ZNF727
215625_at	LOC644450	hypothetical protein LOC644450	1.56502
1566145_s_at	LOC644450	hypothetical protein LOC644450	2.02346
227976_at	LOC644538	hypothetical protein LOC644538	1.58277
230902_at	LOC645323	CDNA clone IMAGE: 5260726	2.44976
238850_at	LOC645323	hypothetical LOC645323	2.41121
1561760_s_at	LOC645513	CDNA clone IMAGE: 5276804	−1.54359
1564200_at	LOC646324	hypothetical LOC646324	1.94425
1568933_at	LOC646627	phospholipase inhibitor	1.90895
215467_x_at	LOC647070	hypothetical LOC647070	1.69676
1561492_at	LOC647107	hypothetical protein LOC647107	4.0125
232696_at	LOC648556	uncharacterized gastric protein ZA43P	2.36077
217998_at	LOC652993 ///	hypothetical LOC652993 /// pleckstrin homology-like domain,	1.57414
	PHLDA1	family A, member 1
1557094_at	LOC653110	hypothetical LOC653110	5.12803
243124_at	LOC653390	RRN3 RNA polymerase I transcription factor homolog (S. cerevisiae)	−1.5339
		pseudogene
216469_at	LOC727867 ///	similar to PRED65 /// zinc finger protein ENSP00000344568-like	1.70529
	LOC729501 ///	/// similar to PR
	LOC729863 ///
	ZNF834
1559322_at	LOC727916	hypothetical protein LOC727916	1.58056
1564856_s_at	LOC727924 ///	hypothetical LOC727924 /// olfactory receptor, family 4,	2.1379
	OR4N4	subfamily N, member 4
1558828_s_at	LOC728264	CDNA FLJ36638 fis, clone TRACH2018950	1.50367
231434_at	LOC728460	similar to FLJ32921 protein	2.51418
1559276_at	LOC728606	hypothetical LOC728606	1.59845
234562_x_at	LOC728678	PREDICTED: Homo sapiens misc_RNA (LOC728678),	2.04162
		miscRNA
1566465_at	LOC728987	MRNA, cDNA DKFZp686I1934 (from clone DKFZp686I1934)	2.74786
214375_at	LOC729222 ///	similar to mKIAA1230 protein /// PTPRF interacting protein,	3.23314
	PPFIBP1	binding protein 1 (1
220167_s_at	LOC729355 ///	similar to TP53TG3 protein /// TP53 target 3	2.68644
	TP53TG3
1563637_at	LOC729652	hypothetical protein LOC729652	1.57589
237899_at	LOC729994	hypothetical LOC729994	−1.50022
233249_at	LOC730200	PREDICTED: Homo sapiens hypothetical LOC730200	3.67813
		(LOC730200), mRNA
237312_at	LOC731477	hypothetical protein LOC731477	1.62866
1570009_at	LOC732096	similar to hCG2040240	4.14937
1563528_at	LOC91149	hypothetical protein LOC91149	1.62561
1557523_at	LOC92270	V-type proton ATPase subunit S1-like protein	2.32742
234861_at	LOC93463	hypothetical protein LOC93463	1.82869
220244_at	LOH3CR2A	loss of heterozygosity, 3, chromosomal region 2, gene A	2.47424
235977_at	LONRF2	LON peptidase N-terminal domain and ring finger 2	2.03367
206960_at	LPAR4	lysophosphatidic acid receptor 4	4.08642
209866_s_at	LPHN3	latrophilin 3	3.07024
230644_at	LRFN5	leucine rich repeat and fibronectin type III domain containing 5	2.28648
230863_at	LRP2	low density lipoprotein-related protein 2	2.0802
1562939_at	LRRC16A	leucine rich repeat containing 16A	1.74525
216149_at	LRRC37B2	leucine rich repeat containing 37, member B2	2.36761
232226_at	LRRC4C	leucine rich repeat containing 4C	2.77481
1556427_s_at	LRRN4CL	LRRN4 C-terminal like	1.55275
206144_at	MAGI1	membrane associated guanylate kinase, WW and PDZ domain	1.70898
		containing 1
225465_at	MAGI1	membrane associated guanylate kinase, WW and PDZ domain	1.58332
		containing 1
226084_at	MAP1B	microtubule-associated protein 1B	2.91601
1562440_at	MAP3K13	Leucine zipper bearing kinase	1.84582
1565131_x_at	MAP3K2	mitogen-activated protein kinase kinase kinase 2	1.69787
1552928_s_at	MAP3K7IP3	mitogen-activated protein kinase kinase kinase 7 interacting	−1.70651
		protein 3
235066_at	MAP4	microtubule-associated protein 4	1.89346
235141_at	MARVELD2	MARVEL domain containing 2	1.74329
233634_at	MARVELD3	MARVEL domain containing 3	1.65824
205018_s_at	MBNL2	muscleblind-like 2 (Drosophila)	−1.60512
1554604_at	MBTPS2	membrane-bound transcription factor peptidase, site 2	1.51324
214884_at	MCF2	DBL mRNA for DBL proto-oncogene splicing variant 1	1.97103
1559427_at	MCF2L	KIAA0362 gene	1.55068
229797_at	MCOLN3	mucolipin 3	−2.39333
212732_at	MEG3	maternally expressed 3 (non-protein coding)	1.61766
235077_at	MEG3	maternally expressed 3 (non-protein coding)	2.45959
207480_s_at	MEIS2	Meis homeobox 2	1.83267
214077_x_at	MEIS3P1	Meis homeobox 3 pseudogene 1	1.90099
211424_x_at	METTL7A	methyltransferase like 7A	2.40031
240814_at	MGC39584	hypothetical gene supported by BC029568	1.77085
238481_at	MGP	matrix Gla protein	1.57297
203637_s_at	MID1	midline 1 (Opitz/BBB syndrome)	2.07411
1552572_a_at	MIPOL1	mirror-image polydactyly 1	1.96747
239468_at	MKX	mohawk homeobox	2.02738
238257_at	MLLT10	Zinc finger/leucine zipper protein (AF10)	1.6337
1569998_at	MMD2	monocyte to macrophage differentiation-associated 2	1.60681
207012_at	MMP16	matrix metallopeptidase 16 (membrane-inserted)	1.87224
208166_at	MMP16	matrix metallopeptidase 16 (membrane-inserted)	2.55402
204575_s_at	MMP19	matrix metallopeptidase 19	−1.70549
220541_at	MMP26	matrix metallopeptidase	26	1.7046
221636_s_at	MOSC2	MOCO sulphurase C-terminal domain containing 2	−1.522
215692_s_at	MPPED2	metallophosphoesterase domain containing 2	2.9265
205395_s_at	MRE11A	MRE11 meiotic recombination 11 homolog A (S. cerevisiae)	−1.60992
220790_s_at	MS4A5	membrane-spanning 4-domains, subfamily A, member 5	1.51834
228473_at	MSX1	CDNA FLJ75656 complete cds, highly similar to Homo sapiens	1.71357
		msh homeo box homolog
205932_s_at	MSX1	msh homeobox 1	2.16058
210319_x_at	MSX2	msh homeobox 2	1.60287
242996_at	MTRF1	mitochondrial translational release factor 1	−1.77601
205675_at	MTTP	microsomal triglyceride transfer protein	1.62218
227241_at	MUC15	mucin 15, cell surface associated	1.84206
216188_at	MYCNOS	v-myc myelocytomatosis viral related oncogene, neuroblastoma	1.93694
		derived (avian) opp
1568926_x_at	MYLK3	myosin light chain kinase 3	2.03024
1568925_at	MYLK3	myosin light chain kinase 3	1.89636
1561503_at	MYLK4	myosin light chain kinase family, member 4	1.51904
237510_at	MYNN	Myoneurin, mRNA (cDNA clone IMAGE: 4721583)	2.07478
244350_at	MYO10	myosin X	2.7656
1554026_a_at	MYO10	myosin X	2.16462
1570141_at	MYO5B	myosin VB	2.21328
211103_at	MYO7A	myosin VIIA	−1.64785
216660_at	MYO7B	myosin VIIB	1.54433
1554507_at	NAALAD2	N-acetylated alpha-linked acidic dipeptidase 2	1.87347
233815_at	NAALAD2	N-acetylated alpha-linked acidic dipeptidase 2	1.93112
228608_at	NALCN	sodium leak channel, non-selective	1.69469
242880_at	NALCN	sodium leak channel, non-selective	1.75222
220184_at	NANOG	Nanog homeobox	2.40254
242639_at	NARG2	NMDA receptor regulated 2	1.98876
236141_at	NBLA00301	Nbla00301	1.84851
237917_at	NBPF8	neuroblastoma breakpoint family, member 8	−1.8445
1563728_at	NCRNA00032	non-protein coding RNA 32	1.54507
1559292_s_at	NCRNA00032	Clone IMAGE: 2275835 C9orf14 mRNA, partial sequence;	2.20902
		alternatively spliced
231491_at	NCRNA00113	non-protein coding RNA 113	2.20943
1569882_at	NCRNA00119	non-protein coding RNA 119	1.50636
220429_at	NDST3	N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3	2.41867
229461_x_at	NEGR1	neuronal growth regulator 1	1.53956
204641_at	NEK2	NIMA (never in mitosis gene a)-related kinase 2	1.82542
206089_at	NELL1	NEL-like 1 (chicken)	1.9916
213438_at	NFASC	neurofascin homolog (chicken)	1.51334
214799_at	NFASC	neurofascin homolog (chicken)	1.74207
236471_at	NFE2L3	nuclear factor (erythroid-derived 2)-like 3	−1.94665
213033_s_at	NFIB	nuclear factor I/B	1.58491
233304_at	NFIB	HMGIC/NFIB fusion protein (HMGIC/NFIB)	1.71392
209289_at	NFIB	nuclear factor I/B	2.33009
209290_s_at	NFIB	nuclear factor I/B	3.26376
213032_at	NFIB	nuclear factor I/B	3.91895
230291_s_at	NFIB	HMGIC/NFIB fusion protein (HMGIC/NFIB)	2.58971
1555141_a_at	NHEDC1	Na+/H+ exchanger domain containing 1	2.54405
1553633_s_at	NHEDC1	Na+/H+ exchanger domain containing 1	2.24905
1564746_at	NHEDC2	Na+/H+ exchanger domain containing 2	1.5816
215228_at	NHLH2	nescient helix loop helix 2	1.86841
1554601_at	NKAIN2	Na+/K+ transporting ATPase interacting 2	1.76903
211024_s_at	NKX2-1	NK2 homeobox 1	1.7883
205893_at	NLGN1	neuroligin 1	2.23077
221933_at	NLGN4X	neuroligin 4, X-linked	1.7674
234762_x_at	NLN	CDNA FLJ39097 fis, clone NTONG2000977, highly similar to	1.62853
		Neurolysin, mitochondri
1552712_a_at	NMNAT2	nicotinamide nucleotide adenylyltransferase 2	1.52782
206045_s_at	NOL4	nucleolar protein 4	2.539
1560974_s_at	NOS1	nitric oxide synthase 1 (neuronal)	1.5825
232158_x_at	NPAL1	NIPA-like domain containing 1	1.9677
220128_s_at	NPAL2	NIPA-like domain containing 2	−1.5032
220316_at	NPAS3	neuronal PAS domain protein 3	1.69165
229281_at	NPAS3	neuronal PAS domain protein 3	1.8588
230412_at	NPAS3	neuronal PAS domain protein 3	2.2537
211585_at	NPAT	nuclear protein, ataxia-telangiectasia locus	1.94524
238844_s_at	NPHP1	nephronophthisis 1 (juvenile)	2.41213
225911_at	NPNT	nephronectin	1.90656
219789_at	NPR3	natriuretic peptide receptor C/guanylate cyclase C	1.73795
		(atrionatriuretic peptide rec
207443_at	NR2E1	nuclear receptor subfamily 2, group E, member 1	1.87607
209119_x_at	NR2F2	nuclear receptor subfamily 2, group F, member 2	2.02969
215073_s_at	NR2F2	nuclear receptor subfamily 2, group F, member 2	1.96135
209121_x_at	NR2F2	nuclear receptor subfamily 2, group F, member 2	1.7412
208241_at	NRG1	neuregulin 1	2.08161
208062_s_at	NRG2	neuregulin 2	1.63978
206879_s_at	NRG2	neuregulin 2	1.72088
232771_at	NRK	Nik related kinase	1.88843
209914_s_at	NRXN1	neurexin 1	1.67775
228547_at	NRXN1	neurexin 1	1.66176
209915_s_at	NRXN1	neurexin 1	1.53885
229649_at	NRXN3	neurexin 3	2.45512
229463_at	NTRK2	neurotrophic tyrosine kinase, receptor, type 2	1.50597
207152_at	NTRK2	neurotrophic tyrosine kinase, receptor, type 2	2.00944
215311_at	NTRK3	neurotrophic tyrosine kinase, receptor, type 3	1.65674
215025_at	NTRK3	neurotrophic tyrosine kinase, receptor, type 3	1.75126
1562775_at	NUDT12	nudix (nucleoside diphosphate linked moiety X)-type motif 12	2.25655
219347_at	NUDT15	nudix (nucleoside diphosphate linked moiety X)-type motif 15	−1.51719
239748_x_at	OCIAD1	OCIA domain containing 1	1.50742
231867_at	ODZ2	odz, odd Oz/ten-m homolog 2 (Drosophila)	3.26427
1554524_a_at	OLFM3	olfactomedin 3	1.97192
207093_s_at	OMG	oligodendrocyte myelin glycoprotein	−1.90409
239911_at	ONECUT2	one cut homeobox 2	1.56079
214111_at	OPCML	opioid binding protein/cell adhesion molecule-like	3.06809
1567657_at	OR2H1	olfactory receptor, family 2, subfamily H, member 1	1.5335
1567656_at	OR2H1	Olfactory receptor (6M1-16 gene), exon E variant 2	1.67337
1567246_at	OR5H1	olfactory receptor, family 5, subfamily H, member 1	2.39135
1567247_at	OR5H1	olfactory receptor, family 5, subfamily H, member 1	2.43277
243531_at	ORAOV1	oral cancer overexpressed 1	−1.53352
211213_at	ORC5L	origin recognition complex, subunit 5-like (yeast)	1.73358
1553931_at	OSTCL	oligosaccharyltransferase complex subunit-like	2.34808
1555251_a_at	OTOF	otoferlin	−1.90077
238994_at	OTUD7B	OTU domain containing 7B	1.54049
206048_at	OVOL2	ovo-like 2 (Drosophila)	3.2046
238409_x_at	OXR1	oxidation resistance	1	2.67129
243335_at	P4HA1	prolyl 4-hydroxylase, alpha polypeptide I	1.7653
220403_s_at	P53AIP1	p53-regulated apoptosis-inducing protein 1	1.58587
220402_at	P53AIP1	p53-regulated apoptosis-inducing protein 1	2.96255
242912_at	P704P	prostate-specific P704P	3.72956
1560770_at	PABPC1	Poly(A) binding protein, cytoplasmic 1, mRNA (cDNA clone	1.63652
		MGC: 12727 IMAGE: 4123269
238865_at	PABPC4L	poly(A) binding protein, cytoplasmic 4-like	2.10195
214607_at	PAK3	p21 protein (Cdc42/Rac)-activated kinase 3	2.88671
210721_s_at	PAK7	p21 protein (Cdc42/Rac)-activated kinase 7	1.74992
228128_x_at	PAPPA	pregnancy-associated plasma protein A, pappalysin 1	2.13807
1559400_s_at	PAPPA	pregnancy-associated plasma protein A, pappalysin 1	1.93398
224940_s_at	PAPPA	pregnancy-associated plasma protein A, pappalysin 1	4.39116
205834_s_at	PART1	prostate androgen-regulated transcript 1	1.8141
210292_s_at	PCDH11X ///	protocadherin 11 X-linked /// protocadherin 11 Y-linked	2.55484
	PCDH11Y
205656_at	PCDH17	protocadherin 17	1.50888
227289_at	PCDH17	protocadherin 17	2.04806
225975_at	PCDH18	protocadherin 18	2.30113
232054_at	PCDH20	protocadherin 20	1.59426
210273_at	PCDH7	protocadherin 7	1.72605
208205_at	PCDHA9	protocadherin alpha 9	1.54772
232415_at	PCDHB13	protocadherin beta 13	1.76909
231726_at	PCDHB14	protocadherin beta 14	1.62133
232099_at	PCDHB16	protocadherin beta 16	2.13788
223927_at	PCDHB9	protocadherin beta 9	1.7009
234515_at	PCGEM1	prostate-specific transcript 1 (non-protein coding)	1.50251
210650_s_at	PCLO	piccolo (presynaptic cytomatrix protein)	1.69469
242662_at	PCSK6	PACE4A-II	2.30596
233547_x_at	PDE1A	phosphodiesterase 1A, calmodulin-dependent	1.80161
231213_at	PDE1A	phosphodiesterase 1A, calmodulin-dependent	1.75945
233549_at	PDE1A	phosphodiesterase 1A, calmodulin-dependent	1.69446
208396_s_at	PDE1A	phosphodiesterase 1A, calmodulin-dependent	2.26838
215575_at	PDE4DIP	phosphodiesterase 4D interacting protein	1.79302
231065_at	PDE6D	P17 protein	−1.55018
1554828_at	PDGFRA	platelet-derived growth factor receptor, alpha polypeptide	1.53439
232288_at	PDXDC1 ///	pyridoxal-dependent decarboxylase domain containing 1 ///	1.65294
	PDXDC2	pyridoxal-dependent de
238957_at	PDXDC2	MRNA; cDNA DKFZp761H1120 (from clone	2.03644
		DKFZp761H1120)
212092_at	PEG10	paternally expressed 10	1.60907
230068_s_at	PEG3	KIAA0287 gene	1.82316
209243_s_at	PEG3 /// ZIM2	paternally expressed 3 /// zinc finger, imprinted 2	2.16162
219642_s_at	PEX5L	peroxisomal biogenesis factor 5-like	1.54143
222019_at	PFDN6	prefoldin subunit 6	−1.51654
240883_at	PFKFB1	6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (EC	1.5229
		2.7.1.105, EC 3.1.3.46)
244321_at	PGAP1	post-GPI attachment to proteins 1	1.62493
215179_x_at	PGF	Placenta growth factor 2 (PIGF-2)	1.53586
1554560_at	PGM5	phosphoglucomutase	5	4.77525
1560431_at	PGM5P1	phosphoglucomutase	5 pseudogene 1	1.50207
234405_s_at	PHAX	phosphorylated adaptor for RNA export	−1.66337
1556369_a_at	PHKG2	phosphorylase kinase, gamma 2 (testis)	−1.66594
210919_at	PHLPP	PH domain and leucine rich repeat protein phosphatase	2.708
217097_s_at	PHTF2	putative homeodomain transcription factor 2	1.54839
237866_at	PID1	phosphotyrosine interaction domain containing 1	1.52656
1558292_s_at	PIGW	phosphatidylinositol glycan anchor biosynthesis, class W	−1.79257
220041_at	PIGZ	phosphatidylinositol glycan anchor biosynthesis, class Z	−1.75754
215129_at	PIK3C2G	phosphoinositide-3-kinase, class 2, gamma polypeptide	1.96389
214868_at	PIWIL1	piwi-like 1 (Drosophila)	2.16549
1563465_at	PKD1L1	polycystic kidney disease 1 like 1	2.06488
203895_at	PLCB4	phospholipase C, beta 4	1.68346
203896_s_at	PLCB4	phospholipase C, beta 4	2.41741
240033_at	PLG	plasminogen	1.56995
207374_at	PLSCR2	phospholipid scramblase 2	1.56409
224421_x_at	PMCHL1	pro-melanin-concentrating hormone-like 1	2.02666
224418_x_at	PMCHL1	pro-melanin-concentrating hormone-like 1	1.90155
224419_x_at	PMCHL1	pro-melanin-concentrating hormone-like 1	2.04898
224422_x_at	PMCHL2	pro-melanin-concentrating hormone-like 2	1.91294
206826_at	PMP2	peripheral myelin protein 2	2.22591
219926_at	POPDC3	popeye domain containing 3	1.64053
1555778_a_at	POSTN	periostin, osteoblast specific factor	1.55784
210809_s_at	POSTN	periostin, osteoblast specific factor	1.68545
1569675_at	POU2AF1	POU class 2 associating factor 1, mRNA (cDNA clone	2.48784
		MGC: 45211 IMAGE: 5554134)
207109_at	POU2F3	POU class 2 homeobox 3	1.72743
207084_at	POU3F2	POU class 3 homeobox 2	1.51578
219195_at	PPARGC1A	peroxisome proliferator-activated receptor gamma, coactivator 1	2.39587
		alpha
232073_at	PPFIA2	protein tyrosine phosphatase, receptor type, f polypeptide	1.76444
		(PTPRF), interacting
204517_at	PPIC	peptidylprolyl isomerase C (cyclophilin C)	2.51701
236142_at	PPIH	U-snRNP-associated cyclophilin (USA-CyP)	−1.72474
223999_at	PPIL2	peptidylprolyl isomerase (cyclophilin)-like 2	1.50516
1555462_at	PPP1R1C	protein phosphatase	1, regulatory (inhibitor) subunit 1C	2.33566
240187_at	PPP1R3C	protein phosphatase	1, regulatory (inhibitor) subunit 3C	1.52454
202886_s_at	PPP2R1B	protein phosphatase 2 (formerly 2A), regulatory subunit A, beta	−1.54317
		isoform
220673_s_at	PPP4R4	protein phosphatase 4, regulatory subunit 4	1.97256
230311_s_at	PRDM6	PR domain containing 6	1.62777
238441_at	PRKAA2	protein kinase, AMP-activated, alpha 2 catalytic subunit	1.64369
227892_at	PRKAA2	protein kinase, AMP-activated, alpha 2 catalytic subunit	1.67124
1554910_at	PRKD3	protein kinase D3	−1.6967
220696_at	PRO0478	PRO0478 protein	2.36786
220883_at	PRO2012	hypothetical protein PRO2012	1.781
208004_at	PROL1	proline rich, lacrimal 1	2.63065
228656_at	PROX1	prospero homeobox 1	1.83495
242119_at	PROX1	Homeodomain protein (Prox 1)	1.93805
229376_at	PROX1	prospero homeobox 1	2.24415
1552455_at	PRUNE2	prune homolog 2 (Drosophila)	2.21968
210195_s_at	PSG1	pregnancy specific beta-1-glycoprotein 1	2.30034
222796_at	PTCD1	pentatricopeptide repeat domain 1	1.61999
209816_at	PTCH1	patched homolog 1 (Drosophila)	1.75809
1552848_a_at	PTCHD1	patched domain containing 1	1.75618
228825_at	PTGR1	prostaglandin reductase	1	2.7707
210355_at	PTHLH	parathyroid hormone-like hormone	1.52732
1555324_at	PTK7	PTK7 protein tyrosine kinase 7	2.09835
209465_x_at	PTN	pleiotrophin	1.77916
211737_x_at	PTN	pleiotrophin	1.62249
208011_at	PTPN22	protein tyrosine phosphatase, non-receptor type 22 (lymphoid)	1.55539
213362_at	PTPRD	protein tyrosine phosphatase, receptor type, D	1.55396
214043_at	PTPRD	protein tyrosine phosphatase, receptor type, D	4.76051
204944_at	PTPRG	protein tyrosine phosphatase, receptor type, G	2.03281
235634_at	PURG	purine-rich element binding protein G	2.04289
215517_at	PYGO1	pygopus homolog 1 (Drosophila)	1.83752
239570_at	RAB1A	GTP-binding protein (RAB1A) mRNA, 3′ untranslated region	−1.61026
241977_s_at	RAB3C	RAB3C, member RAS oncogene family (RAB3C), mRNA	1.93934
224200_s_at	RAD18	RAD18 homolog (S. cerevisiae)	−1.56083
223417_at	RAD18	RAD18 homolog (S. cerevisiae)	−1.61243
234662_at	RAD21L1	RAD21-like 1 (S. pombe)	2.08749
204146_at	RAD51AP1	RAD51 associated protein 1	−1.97583
206591_at	RAG1	recombination activating gene 1	2.08266
242712_x_at	RANBP2 ///	RAN binding protein 2 /// RANBP2-like and GRIP domain	1.6504
	RGPD1 ///	containing 1 /// RANBP2-li
	RGPD2 ///
	RGPD3 ///
	RGPD4 ///
	RGPD5 ///
	RGPD6 ///
	RGPD7 ///
	RGPD8
217201_at	RASAL2	RAS protein activator like 2	1.84564
1557432_at	RASAL2	RAS protein activator like 2	2.14711
217194_at	RASAL2	RAS protein activator like 2	3.48961
1553986_at	RASEF	RAS and EF-hand domain containing	1.63337
1553185_at	RASEF	RAS and EF-hand domain containing	1.64601
1553186_x_at	RASEF	RAS and EF-hand domain containing	1.848
235638_at	RASSF6	Ras association (RalGDS/AF-6) domain family member 6	2.07978
225846_at	RBM35A	RNA binding motif protein 35A	1.61178
219121_s_at	RBM35A	RNA binding motif protein 35A	1.76238
242516_x_at	RBM46	RNA binding motif protein 46	3.82539
1560322_at	RBMS3	RNA binding motif, single stranded interacting protein	1.60171
238447_at	RBMS3	RNA binding motif, single stranded interacting protein	4.85901
209487_at	RBPMS	RNA binding protein with multiple splicing	2.17673
232359_at	RDH11	Vesicle soluble NSF attachment protein receptor (VT11)	1.86356
212398_at	RDX	radixin	1.899
1561720_at	RECQL5	RecQ protein-like 5	3.42158
205923_at	RELN	reelin	1.58794
220276_at	RERGL	RERG/RAS-like	1.7491
203225_s_at	RFK	riboflavin kinase	−1.66609
223673_at	RFX4	regulatory factor X, 4 (influences HLA class II expression)	2.13206
1556354_s_at	RGL3	ral guanine nucleotide dissociation stimulator-like 3	1.56724
1568752_s_at	RGS13	regulator of G-protein signaling 13	2.03693
209071_s_at	RGS5	regulator of G-protein signaling 5	1.55719
237719_x_at	RGS7BP	regulator of G-protein signaling 7 binding protein	2.97708
233409_at	RHBDL3	rhomboid, veinlet-like 3 (Drosophila)	1.6217
238906_s_at	RHOJ	ras homolog gene family, member J	1.71684
1552922_at	RIMS1	regulating synaptic membrane exocytosis 1	1.58145
235153_at	RNF183	ring finger protein 183	1.59993
210931_at	RNF6	ring finger protein (C3H2C3 type) 6	1.9021
226709_at	ROBO2	roundabout, axon guidance receptor, homolog 2 (Drosophila)	1.71534
226766_at	ROBO2	roundabout, axon guidance receptor, homolog 2 (Drosophila)	1.66383
240425_x_at	ROBO2	Roundabout 2 (robo2)	2.35616
242385_at	RORB	RAR-related orphan receptor B	4.22051
1555990_at	RP1-127L4.6	hypothetical protein LOC150297	2.08107
1556222_at	RP11-291L22.2	similar to cell division cycle 10	1.74943
235700_at	RP13-36C9.6	cancer/testis antigen CT45-5	1.55319
204666_s_at	RP5-1000E10.4	suppressor of IKK epsilon	1.58185
235294_at	RP5-1000E10.4	suppressor of IKK epsilon	−1.58872
230661_at	RPESP	RPE-spondin (RPESP), mRNA	1.54079
238375_at	RPL22	Full open reading frame cDNA clone RZPDo834F116D for gene	6.19279
		RPL22, ribosomal prote
238370_x_at	RPL22	Full open reading frame cDNA clone RZPDo834F116D for gene	5.65484
		RPL22, ribosomal prote
215249_at	RPL35A	ribosomal protein L35a	−1.53549
213459_at	RPL37A	ribosomal protein L37a	−1.577
220738_s_at	RPS6KA6	ribosomal protein S6 kinase, 90 kDa, polypeptide 6	1.81745
228186_s_at	RSPO3	R-spondin 3 homolog (Xenopus laevis)	2.10349
1553277_at	RTTN	rotatin	1.55066
215321_at	RUNDC3B	RUN domain containing 3B	2.53893
205528_s_at	RUNX1T1	runt-related transcription factor 1; translocated to, 1 (cyclin D-	2.02137
		related)
205529_s_at	RUNX1T1	runt-related transcription factor 1; translocated to, 1 (cyclin D-	3.23118
		related)
239150_at	S100A1L	Protein S100-A1-like	1.67335
229273_at	SALL1	sal-like 1 (Drosophila)	2.31825
1553411_s_at	SALL3	sal-like 3 (Drosophila)	1.64155
232847_at	SALL3	sal-like 3 (Drosophila)	2.0568
1569443_at	SAMD5	sterile alpha motif domain containing 5	1.50746
228653_at	SAMD5	sterile alpha motif domain containing 5	1.52142
1559882_at	SAMHD1	Full length insert cDNA clone YP80A10	1.63358
1569599_at	SAMSN1	SAMSN1 variant b (SAMSN1) mRNA, complete cds;	1.67178
		alternatively spliced
211423_s_at	SC5DL	sterol-C5-desaturase (ERG3 delta-5-desaturase homolog, S. cerevisiae)-	−1.78404
		like
206667_s_at	SCAMP1	secretory carrier membrane protein 1	3.99037
206021_at	SCAND2	SCAN domain containing 2 pseudogene	1.76903
220232_at	SCD5	stearoyl-CoA desaturase 5	2.02692
1554921_a_at	SCEL	sciellin	1.64729
206884_s_at	SCEL	sciellin	1.98342
59705_at	SCLY	selenocysteine lyase	−1.63837
210853_at	SCN11A	sodium channel, voltage-gated, type XI, alpha subunit	2.60254
1555246_a_at	SCN1A	sodium channel, voltage-gated, type I, alpha subunit	2.29049
210383_at	SCN1A	sodium channel, voltage-gated, type I, alpha subunit	3.19642
229057_at	SCN2A	sodium channel, voltage-gated, type II, alpha subunit	1.98264
212157_at	SDC2	syndecan 2	1.50872
229522_at	SDR42E1	short chain dehydrogenase/reductase family 42E, member 1	−1.52939
206941_x_at	SEMA3E	sema domain, immunoglobulin domain (Ig), short basic domain,	2.31714
		secreted, (semaphor
226492_at	SEMA6D	sema domain, transmembrane domain (TM), and cytoplasmic	1.52645
		domain, (semaphorin) 6D
239889_at	SERP2	Stress-associated endoplasmic reticulum protein family member	1.64374
		2, mRNA (cDNA clon
211361_s_at	SERPINB13	serpin peptidase inhibitor, clade B (ovalbumin), member 13	1.54593
217272_s_at	SERPINB13	serpin peptidase inhibitor, clade B (ovalbumin), member 13	2.91352
240709_at	SEZ6L	seizure related 6 homolog (mouse)-like	1.86136
233753_at	SFRS15	splicing factor, arginine/serine-rich 15	−1.58165
237485_at	SFRS3	Pre-mRNA splicing factor SRp20, 5′UTR region	1.63657
230730_at	SGCD	sarcoglycan, delta (35 kDa dystrophin-associated glycoprotein)	1.56939
228602_at	SGCD	sarcoglycan, delta (35 kDa dystrophin-associated glycoprotein)	2.64714
231938_at	SGOL1	Shugoshin-like 1 (S. pombe), mRNA (cDNA clone	1.93941
		IMAGE: 3861301)
225162_at	SH3D19	SH3-domain containing 19	1.6843
211565_at	SH3GL3	SH3-domain GRB2-like 3	6.2489
213307_at	SHANK2	SH3 and multiple ankyrin repeat domains 2	2.22882
235238_at	SHC4	SHC (Src homology 2 domain containing) family, member 4	2.48968
207570_at	SHOX	short stature homeobox	3.56283
208443_x_at	SHOX2	short stature homeobox 2	1.65982
210135_s_at	SHOX2	short stature homeobox 2	4.81277
1554354_at	SIAE	sialic acid acetylesterase	1.6335
215856_at	SIGLEC15	sialic acid binding Ig-like lectin 15	1.59259
228347_at	SIX1	SIX homeobox 1	1.60659
206634_at	SIX3	SIX homeobox 3	2.19671
206675_s_at	SKIL	SKI-like oncogene	−1.59872
237106_at	SLC11A2	NRAMP2	1.57374
220502_s_at	SLC13A1	solute carrier family 13 (sodium/sulfate symporters), member 1	2.41997
211349_at	SLC15A1	solute carrier family 15 (oligopeptide transporter), member 1	1.63562
205317_s_at	SLC15A2	solute carrier family 15 (H+/peptide transporter), member 2	−1.94245
205234_at	SLC16A4	solute carrier family 16, member 4 (monocarboxylic acid	−1.66979
		transporter 5)
220551_at	SLC17A6	solute carrier family 17 (sodium-dependent inorganic phosphate	2.40381
		cotransporter), m
232232_s_at	SLC22A16	solute carrier family 22 (organic cation/carnitine transporter),	−2.99841
		member 16
234561_at	SLC2A13	solute carrier family 2 (facilitated glucose transporter), member	1.52225
		13
239596_at	SLC30A7	solute carrier family 30 (zinc transporter), member 7	1.91435
220796_x_at	SLC35E1	solute carrier family 35, member E1	1.67755
228060_at	SLC35F1	solute carrier family 35, member F1	2.29249
220786_s_at	SLC38A4	solute carrier family 38, member 4	1.67855
1553126_a_at	SLC39A12	solute carrier family 39 (zinc transporter), member 12	1.66587
228945_s_at	SLC39A8	MRNA, 3′UTR, up-regulated by BCG-CWS	1.67744
210739_x_at	SLC4A4	solute carrier family 4, sodium bicarbonate cotransporter,	1.6053
		member 4
211494_s_at	SLC4A4	solute carrier family 4, sodium bicarbonate cotransporter,	2.49002
		member 4
231424_at	SLC5A12	solute carrier family 5 (sodium/glucose cotransporter), member	3.26263
		12
1554724_at	SLC6A11	solute carrier family 6 (neurotransmitter transporter, GABA),	1.51255
		member 11
1556641_at	SLC7A14	solute carrier family 7 (cationic amino acid transporter, y+	1.50049
		system), member 14
216604_s_at	SLC7A8	solute carrier family 7 (cationic amino acid transporter, y+	1.76482
		system), member 8
1552745_at	SLCO6A1	solute carrier organic anion transporter family, member 6A1	1.63132
236734_at	SLITRK1	SLIT and NTRK-like family, member 1	1.73464
232481_s_at	SLITRK6	SLIT and NTRK-like family, member 6	1.9486
215599_at	SMA4	glucuronidase, beta pseudogene	1.96895
207441_at	SMR3B	submaxillary gland androgen regulated protein 3B	1.78909
1556629_a_at	SNAP25	HUMSNAP25B(F)	2.68011
219511_s_at	SNCAIP	synuclein, alpha interacting protein	1.66212
237834_at	SNCAIP	synuclein, alpha interacting protein	1.86709
232547_at	SNIP	SNAP25-interacting protein	3.23498
202691_at	SNRPD1	small nuclear ribonucleoprotein D1 polypeptide 16 kDa	−1.70602
216850_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	1.74192
1559545_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	2.24102
240204_at	SNRPN	small nuclear ribonucleoprotein polypeptide N	2.35762
220487_at	SNTG2	syntrophin, gamma 2	−1.61256
218705_at	SNX24	sorting nexin 24	−1.55845
239739_at	SNX24	sorting nexin 24	1.99704
241987_x_at	SNX31	sorting nexin 31	3.63912
223666_at	SNX5	sorting nexin	5	−1.61478
1563906_at	SOBP	sine oculis binding protein homolog (Drosophila)	1.59114
209648_x_at	SOCS5	suppressor of cytokine signaling 5	−1.52633
1558815_at	SORBS2	sorbin and SH3 domain containing 2	2.73073
204914_s_at	SOX11	SRY (sex determining region Y)-box 11	2.70367
204913_s_at	SOX11	SRY (sex determining region Y)-box 11	4.13442
223865_at	SOX6	SRY (sex determining region Y)-box 6	1.87491
1570486_at	SOX6	SRY (sex determining region Y)-box 6	1.85225
202936_s_at	SOX9	SRY (sex determining region Y)-box 9	1.53496
202935_s_at	SOX9	SRY (sex determining region Y)-box 9	3.35729
231178_at	SPATA4	spermatogenesis associated 4	1.61457
209891_at	SPC25	SPC25, NDC80 kinetochore complex component, homolog (S. cerevisiae)	1.75386
206318_at	SPINLW1	serine peptidase inhibitor-like, with Kunitz and WAP domains 1	1.7884
		(eppin)
235342_at	SPOCK3	spare/osteonectin, cwcv and kazal-like domains proteglycan	2.41614
		(testican) 3
220456_at	SPTLC3	serine palmitoyltransferase, long chain base subunit 3	2.15437
241961_at	SRD5A2L2	steroid 5 alpha-reductase 2-like 2	3.63908
241734_at	SRFBP1	serum response factor binding protein 1	−1.55343
1554473_at	SRGAP1	SLIT-ROBO Rho GTPase activating protein 1	2.85701
228628_at	SRGAP2P1	SLIT-ROBO Rho GTPase activating protein 2 pseudogene 1	2.17844
214597_at	SSTR2	somatostatin receptor 2	1.79921
215885_at	SSX2	synovial sarcoma, X breakpoint 2	1.80412
208586_s_at	SSX4 /// SSX4B	synovial sarcoma, X breakpoint 4 /// synovial sarcoma, X	1.7382
		breakpoint 4B
206835_at	STATH	statherin	1.86909
204595_s_at	STC1	stanniocalcin 1	1.67438
204597_x_at	STC1	stanniocalcin 1	3.94696
202695_s_at	STK17A	serine/threonine kinase 17a	−1.53066
223883_s_at	STK31	serine/threonine kinase 31	1.59045
231969_at	STOX2	storkhead box 2	3.87778
223245_at	STRBP	spermatid perinuclear RNA binding protein	−1.59889
235180_at	STYX	serine/threonine/tyrosine interacting protein	−1.63483
212354_at	SULF1	sulfatase 1	1.9771
222940_at	SULT1E1	sulfotransferase family 1E, estrogen-preferring, member 1	1.76639
213247_at	SVEP1	sushi, von Willebrand factor type A, EGF and pentraxin domain	1.77875
		containing 1
1553129_at	SVEP1	sushi, von Willebrand factor type A, EGF and pentraxin domain	1.98786
		containing 1
216917_s_at	SYCP1	synaptonemal complex protein 1	2.71601
206740_x_at	SYCP1	synaptonemal complex protein 1	2.55636
215350_at	SYNE1	spectrin repeat containing, nuclear envelope 1	1.84406
202796_at	SYNPO	synaptopodin	−1.54553
225720_at	SYNPO2	synaptopodin 2	2.47627
229053_at	SYT17	CDNA FLJ56448 complete cds, highly similar to Homo sapiens	−2.12139
		synaptotagmin XVII (S
202287_s_at	TACSTD2	tumor-associated calcium signal transducer 2	2.08528
242318_at	TAPT1	Transmembrane anterior posterior transformation 1 (TAPT1),	1.65116
		mRNA
214413_at	TAT	Tyrosine aminotransferase	1.56842
221858_at	TBC1D12	TBC1 domain family, member 12	−1.89833
1563272_at	TBC1D8B	TBC1 domain family, member 8B (with GRAM domain)	1.60724
233633_at	TBL1XR1	Transducin (beta)-like 1X-linked receptor 1, mRNA (cDNA	2.06728
		clone IMAGE: 4754868)
225544_at	TBX3	T-box 3	2.58503
240715_at	TBX5	T-box 5	3.04595
1561254_at	tcag7.1188	hypothetical LOC340340	1.89091
1562664_at	tcag7.929	hypothetical protein LOC286009	1.65909
202823_at	TCEB1	transcription elongation factor B (SIII), polypeptide 1 (15 kDa,	−1.5985
		elongin C)
206286_s_at	TDGF1 ///	teratocarcinoma-derived growth factor 1 /// teratocarcinoma-	1.64616
	TDGF3	derived growth facto
214600_at	TEAD1	TEA domain family member 1 (SV40 transcriptional enhancer	1.68001
		factor)
204653_at	TFAP2A	transcription factor AP-2 beta (activating enhancer binding	1.80715
		protein 2 alpha)
214451_at	TFAP2B	transcription factor AP-2 beta (activating enhancer binding	2.80351
		protein 2 beta)
233987_at	TFAP2D	transcription factor AP-2 delta (activating enhancer binding	1.66515
		protein 2 delta)
1566931_at	TFB2M	Transcription factor B2, mitochondrial, mRNA (cDNA clone	1.53869
		IMAGE: 5311413)
1566932_x_at	TFB2M	Transcription factor B2, mitochondrial, mRNA (cDNA clone	1.53363
		IMAGE: 5311413)
215447_at	TFPI	Tissue factor pathway inhibitor (lipoprotein-associated	4.00815
		coagulation inhibitor),
228121_at	TGFB2	transforming growth factor, beta 2	2.06407
235653_s_at	THAP6	THAP domain containing 6	−1.78358
203083_at	THBS2	thrombospondin 2	1.79394
204776_at	THBS4	thrombospondin 4	−1.51372
219044_at	THNSL2	threonine synthase-like 2 (S. cerevisiae)	−1.81461
222835_at	THSD4	thrombospondin, type I, domain containing 4	4.52581
230008_at	THSD7A	thrombospondin, type I, domain containing 7A	1.71666
214920_at	THSD7A	thrombospondin, type I, domain containing 7A	1.86908
210800_at	TIMM8A	translocase of inner mitochondrial membrane 8 homolog A	3.55929
		(yeast)
202011_at	TJP1	tight junction protein 1 (zona occludens 1)	2.15499
1555071_at	TLL1	tolloid-like 1	1.86768
215008_at	TLL2	tolloid-like 2	3.33235
230061_at	TM4SF18	MRNA; cDNA DKFZp313N1532 (from clone	1.61636
		DKFZp313N1532)
220639_at	TM4SF20	transmembrane 4 L six family member 20	1.53906
228610_at	TM9SF3	CDNA FLJ90343 fis, clone NT2RP2002824, highly similar to	1.79254
		Transmembrane 9 superfa
1564591_a_at	TMC1	transmembrane channel-like 1	1.87321
1553636_at	TMCO5A	transmembrane and coiled-coil domains 5A	1.91589
1554866_at	TMEM135	transmembrane protein 135	1.70254
238497_at	TMEM136	transmembrane protein 136	1.66054
239593_at	TMEM213	transmembrane protein 213	1.53796
209655_s_at	TMEM47	transmembrane protein 47	1.52814
204807_at	TMEM5	transmembrane protein 5	−1.53392
156377_at	TMEM67	transmembrane protein 67	2.34523
1563646_a_at	TMEM67	transmembrane protein 67	2.05536
226483_at	TMEM68	transmembrane protein 68	−1.58264
213024_at	TMF1	TATA element modulatory factor 1	−1.513
220431_at	TMPRSS11E ///	transmembrane protease, serine 11E /// transmembrane protease,	1.56517
	TMPRSS11E2	serine 11E2
1555707_at	TNAP	TRAFs and NIK-associated protein	2.65475
216005_at	TNC	Tenascin	2.11502
216042_at	TNFRSF25	tumor necrosis factor receptor superfamily, member 25	−1.54437
1557278_s_at	TNPO1	Transportin 1, mRNA (cDNA clone MGC: 17116	1.686
		IMAGE: 4178989)
232750_at	TNS1	Tensin 1, mRNA (cDNA clone IMAGE: 4546443)	2.98094
237469_at	TOP2A	Topoisomerase (DNA) II alpha 170 kDa, mRNA (cDNA clone	1.75261
		IMAGE: 4101949)
220205_at	TPTE	transmembrane phosphatase with tensin homology	2.99568
1556876_s_at	TPTEps1	TPTE pseudogene 1	3.4786
244334_at	TRAM1L1	translocation associated membrane protein 1-like 1	1.80692
1552791_a_at	TRDN	triadin	1.71337
222754_at	TRNT1	tRNA nucleotidyl transferase, CCA-adding, 1	−1.57097
210814_at	TRPC3	transient receptor potential cation channel, subfamily C, member 3	2.29944
234407_s_at	TRPC7	transient receptor potential cation channel, subfamily C, member 7	2.14569
206479_at	TRPM1	transient receptor potential cation channel, subfamily M, member 1	1.86699
240386_at	TRPM1	Homo sapiens, clone IMAGE: 4332660, mRNA	1.91651
216452_at	TRPM3	transient receptor potential cation channel, subfamily M, member 3	1.64176
233022_at	TRPM3	transient receptor potential cation channel, subfamily M, member 3	2.69873
203824_at	TSPAN8	tetraspanin 8	1.91188
215146_s_at	TTC28	tetratricopeptide repeat domain 28	1.58487
1556666_a_at	TTC6	tetratricopeptide repeat domain 6	3.47481
240369_at	TTC7A	Tetratricopeptide repeat domain 7A, mRNA (cDNA clone	−1.55993
		IMAGE: 5113102)
242771_at	TTN	Titin	−1.82217
210614_at	TTPA	tocopherol (alpha) transfer protein	1.58646
230891_at	TUBE1	Tubulin, epsilon 1, mRNA (cDNA clone MGC: 33949	2.16675
		IMAGE: 5298159)
239742_at	TULP4	Full length insert cDNA clone YU79H10	1.85499
213943_at	TWIST1	twist homolog 1 (Drosophila)	4.94261
220869_at	UBA6	ubiquitin-like modifier activating enzyme 6	1.7396
1569262_x_at	UBE2CBP	ubiquitin-conjugating enzyme E2C binding protein	2.10912
233327_at	UBE2CBP	ubiquitin-conjugating enzyme E2C binding protein	2.67633
234163_at	UBE3A	E6-AP isoform-III	2.16744
234166_at	UBE3A	E6-AP isoform-III	1.65174
1555834_at	UCHL1	Protein gene product (PGP) 9.5	1.73702
221304_at	UGT1A10 ///	UDP glucuronosyltransferase 1 family, polypeptide A10 /// UDP	2.06331
	UGT1A6 ///	glucuronosyltransf
	UGT1A7 ////
	UGT1A8
221305_s_at	UGT1A6 ///	UDP glucuronosyltransferase 1 family, polypeptide A6 /// UDP	2.18416
	UGT1A8 ///	glucuronosyltransfe
	UGT1A9
211682_x_at	UGT2B28	UDP glucuronosyltransferase 2 family, polypeptide B28	2.56318
226899_at	UNC5B	unc-5 homolog B (C. elegans)	2.95198
214640_at	UNC93A	unc-93 homolog A (C. elegans)	1.66307
214382_at	UNC93A	unc-93 homolog A (C. elegans)	1.71701
1560320_a_at	UNQ2963	hypothetical protein LOC283314	−1.53983
221173_at	USH1C	Usher syndrome 1C (autosomal recessive, severe)	1.52879
207706_at	USH2A	Usher syndrome 2A (autosomal recessive, mild)	1.87956
232621_at	USP48	ubiquitin specific peptidase 48	1.77813
1555065_x_at	USP6	ubiquitin specific peptidase 6 (Tre-2 oncogene)	1.77628
227399_at	VGLL3	vestigial like 3 (Drosophila)	1.72088
220327_at	VGLL3	vestigial like 3 (Drosophila)	1.88289
203844_at	VHL	von Hippel-Lindau tumor suppressor	1.64109
203106_s_at	VPS41	vacuolar protein sorting 41 homolog (S. cerevisiae)	−1.70572
1561200_at	VWA3B	von Willebrand factor A domain containing 3B	1.90857
1552430_at	WDR17	WD repeat domain 17	2.05322
219538_at	WDR5B	WD repeat domain 5B	−1.61334
242162_at	WDR69	WD repeat domain 69	1.51724
220769_s_at	WDR78	WD repeat domain 78	2.25954
206954_at	WIT1	Wilms tumor upstream neighbor 1	2.72357
213425_at	WNT5A	wingless-type MMTV integration site family, member 5A	1.52031
205990_s_at	WNT5A	wingless-type MMTV integration site family, member 5A	2.06024
206067_s_at	WT1	Wilms tumor	1	1.72928
237656_at	WWC2	CDNA FLJ51450 complete cds, highly similar to Claudin-22	1.97362
207598_x_at	XRCC2	X-ray repair complementing defective repair in Chinese hamster	1.69611
		cells 2
214776_x_at	XYLB	xyluolkinase homolog (H. influenzae)	1.87664
1569683_at	XYLB	xyluolkinase homolog (H. influenzae)	1.60808
224895_at	YAP1	Yes-associated protein 1, 65 kDa	2.12127
206169_x_at	ZC3H7B	zinc finger CCCH-type containing 7B	1.55615
216844_at	ZC3H7B	zinc finger CCCH-type containing 7B	2.3575
1553781_at	ZC3HAV1L	zinc finger CCCH-type, antiviral 1-like	2.0001
219917_at	ZCCHC4	zinc finger, CCHC domain containing 4	−1.52373
231946_at	ZFHX2	zinc finger homeobox 2	1.53322
241700_at	ZFHX4	zinc finger homeobox 4	1.74443
222237_s_at	ZFP112	zinc finger protein 112 homolog (mouse)	−1.55145
211773_s_at	ZKSCAN3	zinc finger with KRAB and SCAN domains 3	−1.52752
1552947_x_at	ZNF114	zinc finger protein 114	1.90546
1552946_at	ZNF114	zinc finger protein 114	2.52625
207402_at	ZNF132	zinc finger protein 132	−1.58945
1558184_s_at	ZNF17	zinc finger protein 17	−1.56615
1568644_at	ZNF208	zinc finger protein 208	2.29695
1568646_x_at	ZNF208	zinc finger protein 208	3.20902
243456_at	ZNF214	zinc finger protein 214	1.83302
1557322_at	ZNF230	zinc finger protein 230	−1.76902
1559449_a_at	ZNF254	CDNA FLJ58216 complete cds, highly similar to Zinc finger	−2.34406
		protein 539
215048_at	ZNF280B	zinc finger protein 280B	1.52294
236328_at	ZNF285A	zinc finger protein 285A	−1.73084
216710_x_at	ZNF287	zinc finger protein 287	1.92695
227680_at	ZNF326	zinc finger protein 326	−1.60787
224276_at	ZNF33A	zinc finger protein 33A	1.76911
1562743_at	ZNF33B	Zinc finger protein 33B (ZNF33B), mRNA	1.50959
233169_at	ZNF350	zinc finger protein 350	−1.54751
214761_at	ZNF423	zinc finger protein 423	1.68652
219848_s_at	ZNF432	zinc finger protein 432	−1.52766
205928_at	ZNF443	zinc finger protein 443	−1.58322
226575_at	ZNF462	zinc finger protein 462	2.79327
244007_at	ZNF462	zinc finger protein 462	2.05007
1555368_x_at	ZNF479	zinc finger protein 479	3.58093
1555367_at	ZNF479	zinc finger protein 479	3.75576
1559988_at	ZNF483	zinc finger protein 483	2.28434
1557616_at	ZNF496	zinc finger protein 496	−1.53565
226676_at	ZNF521	zinc finger protein 521	2.55441
226592_at	ZNF618	zinc finger protein 618	1.51197
232272_at	ZNF624	zinc finger protein 624	−1.60359
1553247_a_at	ZNF709	zinc finger protein 709	−1.6001
1560201_at	ZNF713	zinc finger protein 713	1.5002
1553885_x_at	ZNF99	zinc finger protein 99	1.66616
228330_at	ZUFSP	zinc finger with UFM1-specific peptidase domain	−1.55835
1564685_a_at	—	—	1.83044
1566896_at	—	—	1.81016
238137_at	—	—	1.61463
1562201_x_at	—	—	1.69439
241648_at	—	—	−1.52957
236996_at	—	—	−1.54814
1567706_at	—	—	1.9772
239082_at	—	—	1.62335
241235_at	—	—	−1.5976
244767_at	—	—	−1.56631
233424_at	—	—	1.90728
243655_x_at	—	—	1.52941
236395_at	—	—	−1.5143
239903_at	—	—	1.61809
1566645_at	—	—	1.5476
1562341_at	—	—	1.52441
242952_at	—	—	1.55967
1559807_at	—	—	1.70594
238155_at	—	—	−1.5566
1566550_at	—	—	1.54738
242797_x_at	—	—	−1.86201
242170_at	—	—	−1.89134
1570098_at	—	—	1.82945
1559524_at	—	—	−1.71546
239606_at	—	—	−1.53539
1566544_at	—	—	1.61104
242133_s_at	—	—	1.56343
1556760_a_at	—	—	2.00828
1563461_at	—	—	1.53995
1570645_at	—	—	1.55841
240730_at	—	—	1.61181
236602_at	—	—	1.52722
242122_at	—	—	−1.50641
1559410_at	—	—	1.7089
234100_at	—	—	−1.52272
239856_at	—	—	−2.23215
229243_at	—	—	−1.73048
231465_at	—	—	1.62758
1562208_a_at	—	—	1.87064
1561149_at	—	—	1.52562
240642_at	—	—	−1.71584
1557658_at	—	—	−1.61047
230503_at	—	—	1.60016
242494_at	—	—	1.6192
1561956_at	—	—	1.59298
242495_at	—	—	1.57521
222320_at	—	—	1.61706
237886_at	—	—	1.53331
1565788_at	—	—	1.65726
240133_x_at	—	—	1.88894
242074_at	—	—	−1.54665
215029_at	—	—	−1.61964
1568785_a_at	—	—	1.52688
243381_at	—	—	1.63013
216173_at	—	—	1.57894
240688_at	—	—	1.52689
243584_at	—	—	1.76235
231136_at	—	—	1.50646
1569833_at	—	—	1.60643
230168_at	—	—	−1.93736
1564744_at	—	—	1.63372
1562010_x_at	—	—	1.50535
228734_at	—	—	−1.67929
1560717_at	—	—	1.67536
243356_at	—	—	1.72703
1562935_at	—	—	1.5956
240973_s_at	—	—	−1.53876
207471_at	—	—	1.75431
222246_at	—	—	1.84054
237102_at	—	—	1.73952
220871_at	—	—	1.80151
228643_at	—	—	−1.6237
233180_at	—	—	2.25381
1559709_at	—	—	1.69535
242296_x_at	—	—	1.56148
1562456_at	—	—	1.66178
1556518_at	—	—	1.537
233579_at	—	—	2.32946
1563531_at	—	—	1.91261
216757_at	—	—	1.75028
234612_at	—	—	1.54801
1562835_at	—	—	1.7128
234224_at	—	—	1.5186
242115_at	—	—	1.5505
1569527_at	—	—	−1.54022
238415_at	—	—	1.53194
226231_at	—	—	−1.79439
240506_at	—	—	1.60003
240469_at	—	—	1.62514
1557885_at	—	—	1.52753
237356_at	—	—	1.93218
242202_at	—	—	1.57335
236778_at	—	—	1.60299
240355_at	—	—	−1.66821
242142_at	—	—	1.80096
236038_at	—	—	2.10931
1557434_at	—	—	1.53917
227051_at	—	—	−1.88686
1567304_at	—	—	1.60926
239819_at	—	—	1.56334
1563054_at	—	—	1.71697
1557921_s_at	—	—	1.68215
242321_at	—	—	2.20104
1561135_at	—	—	1.73638
1566787_at	—	—	1.59838
239649_at	—	—	1.65668
214645_at	—	—	1.55285
232459_at	—	—	1.82556
243236_at	—	—	−1.70988
1560094_at	—	—	−1.68062
237628_at	—	—	1.51201
244551_at	—	—	−1.66189
243345_at	—	—	−1.65084
240442_at	—	—	1.66955
1560372_at	—	—	2.10286
1566504_at	—	—	1.56292
239986_at	—	—	1.53033
1561319_at	—	—	1.62652
234560_at	—	—	1.68465
1560258_a_at	—	—	1.50646
239863_at	—	—	−1.97398
234064_at	—	—	2.03588
238718_at	—	—	1.68987
244016_at	—	—	1.80815
217038_at	—	—	2.36071
236659_x_at	—	—	1.57533
1566772_at	—	—	1.61228
1566809_a_at	—	—	1.79265
244333_at	—	—	1.65689
230294_at	—	—	−1.55001
1564479_a_at	—	—	1.72664
215864_at	—	—	2.03128
1563477_at	—	—	2.05179
1570213_at	—	—	1.98433
217137_x_at	—	—	2.033
237912_at	—	—	1.82582
241220_at	—	—	1.54608
242166_at	—	—	1.56101
237134_at	—	—	1.84799
238372_s_at	—	—	2.37201
239536_at	—	—	−1.66473
227857_at	—	—	1.56563
1559664_at	—	—	1.60616
240267_at	—	—	1.51777
1564391_at	—	—	1.97908
236161_at	—	—	1.64402
233786_at	—	—	1.81531
1567611_at	—	—	−1.50961
222298_at	—	—	1.58123
232805_at	—	—	1.59909
236678_at	—	—	1.8314
241057_x_at	—	—	1.56362
1556239_a_at	—	—	−1.7364
1558719_s_at	—	—	−1.86612
240658_at	—	—	1.58761
242564_at	—	—	−1.77191
241100_at	—	—	1.89642
236219_at	—	—	−1.78149
240245_at	—	—	1.74041
1561328_at	—	—	1.62167
237231_at	—	—	−1.50546
1558869_at	—	—	1.75081
1554043_a_at	—	—	−1.65188
241030_at	—	—	1.89393
233306_at	—	—	1.8777
1565874_at	—	—	1.63558
230874_at	—	—	−2.06833
1569661_at	—	—	1.59665
237742_at	—	—	1.61044
227985_at	—	—	−1.82784
1566867_at	—	—	1.94122
1564773_x_at	—	—	1.54988
1562053_at	—	—	−2.06402
235188_at	—	—	1.84682
1557512_at	—	—	−1.627
242007_at	—	—	−1.69897
243455_at	—	—	1.61965
239868_at	—	—	1.5129
1561417_x_at	—	—	1.60574
219367_s_at	—	—	1.53187
236394_at	—	—	1.76477
1561134_at	—	—	1.54734
242468_at	—	—	1.97864
1566994_at	—	—	2.10394
210679_x_at	—	—	1.5028
243636_s_at	—	—	1.69661
234588_at	—	—	1.61426
1566995_at	—	—	2.12757
1566096_x_at	—	—	2.08387
233187_s_at	—	—	−1.54128
227745_at	—	—	−1.73547
1557443_s_at	—	—	1.60801
1561161_at	—	—	1.81185
240997_at	—	—	1.65329
1561689_at	—	—	1.65238
241163_at	—	—	1.59299
234248_at	—	—	1.55099
1562065_at	—	—	1.74757
239437_at	—	—	−1.80734
1569208_a_at	—	—	1.93479
1559737_at	—	—	1.72324
240016_at	—	—	1.58788
235666_at	—	—	1.57665
210914_at	—	—	1.51724
233445_at	—	—	1.81438
1565825_at	—	—	1.56204
238203_at	—	—	1.70123
1562327_at	—	—	1.59003
1570316_at	—	—	1.78431
242303_at	—	—	1.7273
1563001_at	—	—	1.56578
1562864_at	—	—	1.54738
222168_at	—	—	1.97664
1562091_at	—	—	1.51347
1566424_at	—	—	1.63682
232962_x_at	—	—	1.69709
235831_at	—	—	1.70453
233861_at	—	—	2.22299
215278_at	—	—	1.71066
242599_at	—	—	1.62169
1565879_at	—	—	1.86352
241002_at	—	—	1.69313
241142_at	—	—	−1.67262
232800_at	—	—	2.29403
242505_at	—	—	1.57494
1558714_at	—	—	1.9751
243014_at	—	—	1.58464
240101_at	—	—	−1.75992
232541_at	—	—	1.55706
241665_x_at	—	—	1.7135
240468_at	—	—	1.92795
215405_at	—	—	1.98124
240800_x_at	—	—	1.60351
221120_at	—	—	1.53838
237332_at	—	—	1.5951
1563036_at	—	—	1.63532
1557659_a_at	—	—	−2.08984
233293_at	—	—	1.51923
242811_x_at	—	—	1.70854
1556439_at	—	—	1.69729
1560453_at	—	—	1.82015
1569779_at	—	—	1.61263
237525_at	—	—	1.51511
240989_at	—	—	1.61747
234606_at	—	—	1.54255
234692_at	—	—	1.61537
216756_at	—	—	1.65304
241637_at	—	—	2.17642
1556656_at	—	—	1.68075
235017_s_at	—	—	1.7341
233130_at	—	—	1.82787
233779_x_at	—	—	1.51862
237355_at	—	—	1.54889
232850_at	—	—	1.55839
230020_at	—	—	−1.8275
243454_at	—	—	2.15818
237573_at	—	—	1.82449
234036_x_at	—	—	1.82885
243666_at	—	—	2.20715
1568736_s_at	—	—	1.83385
215539_at	—	—	1.57174
1556504_at	—	—	1.51528
221144_at	—	—	1.6864
239459_s_at	—	—	2.16772
1552975_x_at	—	—	1.63565
1562727_at	—	—	1.87879
233450_at	—	—	1.82759
241303_x_at	—	—	1.51058
236617_at	—	—	2.04757
1562473_at	—	—	1.52865
1556650_at	—	—	1.53931
238395_at	—	—	1.84075
234597_at	—	—	2.57012
240046_at	—	—	1.75115
237526_at	—	—	1.57771
237492_at	—	—	1.70165
1563351_at	—	—	1.57794
227140_at	—	—	2.59379
216187_x_at	—	—	1.58094
236187_s_at	—	—	1.71841
228842_at	—	—	−1.51876
234532_at	—	—	1.84698
234219_at	—	—	1.83545
242189_at	—	—	1.58063
241203_at	—	—	1.57795
240580_at	—	—	1.77583
1565576_at	—	—	1.51264
242755_at	—	—	2.01686
1568648_a_at	—	—	1.98415
1562718_at	—	—	1.64374
239017_at	—	—	1.54796
1563427_at	—	—	1.62296
242857_at	—	—	−1.7551
1557758_at	—	—	1.8066
1559086_at	—	—	1.85777
241758_at	—	—	1.67733
236564_at	—	—	−1.68533
233721_x_at	—	—	1.86315
202015_x_at	—	—	1.99169
240640_at	—	—	1.51291
1557861_at	—	—	1.75142
240858_at	—	—	1.54478
1559695_a_at	—	—	1.82202
244891_x_at	—	—	1.6181
240297_at	—	—	1.62096
1558444_at	—	—	2.92859
1570482_at	—	—	2.57201
1563055_at	—	—	1.58052
1567303_at	—	—	1.9115
231037_at	—	—	1.77578
1564690_at	—	—	3.09408
1561129_at	—	—	1.5641
244045_at	—	—	2.06161
1560352_at	—	—	1.84388
241130_at	—	—	1.58428
232268_at	—	—	1.57907
1566768_at	—	—	1.84415
241173_at	—	—	1.86436
1562760_at	—	—	1.72579
1562588_at	—	—	1.94416
1566763_at	—	—	2.04467
1569740_at	—	—	1.64645
240290_at	—	—	1.67943
237496_at	—	—	2.06865
1567379_at	—	—	1.62299
244125_at	—	—	2.57599
235445_at	—	—	1.91795
1555174_at	—	—	1.58019
216643_at	—	—	1.89215
1569983_at	—	—	2.39576
1560429_at	—	—	2.04382
1563386_at	—	—	1.76382
244511_at	—	—	1.62772
1570350_at	—	—	1.61993
241487_at	—	—	1.66578
1567913_at	—	—	5.71757
1562686_at	—	—	1.74144
1565860_at	—	—	2.96918
244510_at	—	—	2.46633
237622_at	—	—	−2.61939
1557780_at	—	—	1.71847
239520_at	—	—	1.53506
243034_at	—	—	1.5628
238571_at	—	—	1.80516
232113_at	—	—	2.22875
242641_at	—	—	1.61615
234579_at	—	—	1.55619
1566842_at	—	—	1.75893
215587_x_at	—	—	1.53373
236740_at	—	—	1.8285
224549_x_at	—	—	1.68422
233276_at	—	—	1.62961
1561256_at	—	—	1.92386
1566094_at	—	—	2.44114
224234_at	—	—	1.5266
244098_at	—	—	1.6926
234428_at	—	—	2.25705
1562720_at	—	—	1.91297
243147_x_at	—	—	1.67593
1569344_a_at	—	—	2.19681
235560_at	—	—	1.6268
228504_at	—	—	1.72391
1556985_at	—	—	1.79627
215628_x_at	—	—	1.56039
1562086_at	—	—	1.57298
222372_at	—	—	1.84973
1566582_x_at	—	—	1.79715
233958_at	—	—	1.55915
243008_at	—	—	1.64372
1553275_s_at	—	—	1.89002
243322_at	—	—	1.65429
234825_at	—	—	1.73469
244609_at	—	—	1.85048
215615_x_at	—	—	1.53488
1561528_at	—	—	1.55697
241852_at	—	—	1.60268
1558489_at	—	—	2.34982
239672_at	—	—	1.66417
1560087_a_at	—	—	1.92031
1556904_at	—	—	2.30213
244724_at	—	—	1.60549
241310_at	—	—	2.15657
241655_at	—	—	1.54091
234625_at	—	—	1.58324
231616_at	—	—	2.13008
236697_at	—	—	1.5915
235642_at	—	—	1.70455
241897_at	—	—	2.12195
236670_s_at	—	—	2.10982
240578_at	—	—	1.61716
1562235_s_at	—	—	1.55351
1562687_x_at	—	—	1.8282
1556805_at	—	—	2.61186
237727_at	—	—	1.66554
215284_at	—	—	2.05102
228740_at	—	—	1.82664
244769_at	—	—	1.95537
227484_at	—	—	1.51603
233755_at	—	—	1.86698
227126_at	—	—	2.10379
224429_x_at	—	—	1.56535
1556796_at	—	—	2.47359
221146_at	—	—	1.70639
233265_at	—	—	1.84813
234494_x_at	—	—	1.7031
1556206_at	—	—	1.82973
244384_at	—	—	1.92957
236466_at	—	—	1.7519
238536_at	—	—	1.76454
1561591_at	—	—	1.63671
232808_at	—	—	1.87054
1563052_at	—	—	3.05615
1556813_at	—	—	1.66613
233402_at	—	—	1.53209
238847_at	—	—	2.49299
237483_at	—	—	2.00055
234753_x_at	—	—	1.87523
220820_at	—	—	1.58991
1562332_at	—	—	1.92188
1562905_at	—	—	1.56404
1561217_at	—	—	1.75568
1561121_at	—	—	1.52528
243762_at	—	—	1.60241
236650_at	—	—	1.89552
230577_at	—	—	1.71798
1569753_at	—	—	2.20368
233224_at	—	—	−1.51535
241479_at	—	—	1.90387
1569491_at	—	—	1.79905
237832_at	—	—	2.86311
235733_at	—	—	1.90522
1568803_at	—	—	1.66131
237491_at	—	—	2.70143
216151_at	—	—	1.59221
1556352_at	—	—	1.73928
229490_s_at	—	—	2.20922
1570596_at	—	—	1.65322
237600_at	—	—	1.64121
211374_x_at	—	—	1.57283
216110_x_at	—	—	1.66876
240152_at	—	—	2.07123
240949_x_at	—	—	2.6364
1566968_at	—	—	1.8345
216524_x_at	—	—	1.52057
242188_at	—	—	1.67993
1560690_at	—	—	1.50865
240060_at	—	—	1.50178
237946_at	—	—	2.74367
220837_at	—	—	1.76967
229330_at	—	—	−1.52841
1566666_at	—	—	2.15745
240474_x_at	—	—	1.54025
237903_at	—	—	1.68116
1564567_at	—	—	2.86081
227010_at	—	—	−1.54551
1562507_at	—	—	2.46383
1562544_at	—	—	1.83332
1560891_a_at	—	—	1.60154
233714_at	—	—	2.13082
244259_s_at	—	—	1.69439
243279_at	—	—	2.03405
234755_x_at	—	—	1.52681
241639_at	—	—	2.0758
234667_at	—	—	1.61766
216625_at	—	—	1.54839
244156_at	—	—	2.63578
1556683_x_at	—	—	1.50421
230785_at	—	—	1.50472
232495_x_at	—	—	1.50721
238361_s_at	—	—	2.25068
217619_x_at	—	—	1.54826
1560111_at	—	—	1.80542
236184_at	—	—	2.09878
235629_at	—	—	1.52947
242236_at	—	—	2.6709
217579_x_at	—	—	1.6302
233240_at	—	—	1.58366
222296_at	—	—	1.66123
232592_at	—	—	1.67559
237998_at	—	—	1.95045
242559_at	—	—	1.73911
243240_at	—	—	1.812
241253_at	—	—	1.53832
241069_at	—	—	2.1882
238310_at	—	—	1.68293
1564798_at	—	—	1.74183
217524_x_at	—	—	1.55266
240427_at	—	—	2.39407
217713_x_at	—	—	1.65536
240450_at	—	—	2.21304
237893_at	—	—	2.06445
241132_at	—	—	2.13802
237267_at	—	—	1.89267
1564236_at	—	—	1.69733
1558473_at	—	—	1.83005
1557519_at	—	—	−1.89371
1569231_x_at	—	—	1.6864
241008_at	—	—	1.54943
1561445_at	—	—	1.55856
234571_at	—	—	1.73178
234083_at	—	—	2.037
241656_at	—	—	1.55124
1563012_x_at	—	—	1.50488
1560476_at	—	—	2.17694
1561564_at	—	—	2.75205
233118_at	—	—	1.79787
233702_x_at	—	—	1.54804
1563091_at	—	—	1.67395
1559450_at	—	—	1.77421
244793_at	—	—	1.85576
233622_x_at	—	—	1.51571
241223_x_at	—	—	1.69464
239604_at	—	—	2.18244
216158_at	—	—	1.80396
1556817_a_at	—	—	2.10569
1570099_at	—	—	1.50845
1561692_at	—	—	2.64312
242795_at	—	—	3.20031
1559375_s_at	—	—	1.57452
1569794_at	—	—	1.79312
1562933_at	—	—	1.7812
1561305_at	—	—	1.51196
233502_at	—	—	3.43598
244588_at	—	—	1.86108
240783_at	—	—	2.8921
235739_at	—	—	1.88882
233273_at	—	—	2.07697
1565873_at	—	—	1.75922
242881_x_at	—	—	2.91173
1563568_at	—	—	1.89445
1569755_at	—	—	1.86666
242391_at	—	—	2.54095
1565637_at	—	—	2.44504
241657_at	—	—	1.65304
232957_x_at	—	—	2.28244
233683_at	—	—	2.15259
237065_s_at	—	—	−2.23415
1566597_at	—	—	2.38873
239849_at	—	—	2.49616
1564358_at	—	—	3.57914
233152_x_at	—	—	1.5398
243473_at	—	—	1.8121
216094_at	—	—	2.20104
1568589_at	—	—	2.83131
1555925_at	—	—	3.50923
243572_at	—	—	1.7936
241186_at	—	—	2.07335
239340_at	—	—	3.10534
243192_at	—	—	1.79294
1569230_at	—	—	1.89893
215062_at	—	—	1.66817
1561187_at	—	—	1.53178
243763_x_at	—	—	2.00712
1563329_s_at	—	—	1.93939
238826_x_at	—	—	1.63927
238298_at	—	—	1.92448
205772_s_at	—	—	1.92683
231482_at	—	—	1.9948
242605_at	—	—	1.68979
1565565_at	—	—	1.67957
1562945_at	—	—	1.51982
1556392_a_at	—	—	1.8825
243929_at	—	—	2.32352
1561509_at	—	—	1.59259
1555601_at	—	—	1.81067
232324_x_at	—	—	1.53814
238184_at	—	—	1.50493
1567008_at	—	—	2.21042
243706_at	—	—	1.82234
239514_at	—	—	2.26505
234433_at	—	—	2.20167
240067_at	—	—	1.94901
1562263_at	—	—	1.83224
237850_at	—	—	1.60944
222299_x_at	—	—	1.80516
1557215_at	—	—	1.82993
239985_at	—	—	1.67697
243877_at	—	—	1.65948
1569656_at	—	—	1.83943
239344_at	—	—	1.53249
1561631_at	—	—	1.67024
237365_at	—	—	1.70238
243936_x_at	—	—	2.23539
216337_at	—	—	1.56682
1570423_at	—	—	2.37274
1558672_at	—	—	1.65888
1564580_at	—	—	2.5145
1562923_at	—	—	1.52114
237951_at	—	—	1.6943
242890_at	—	—	1.88508
234805_at	—	—	1.76687
239311_at	—	—	1.55589
1565861_at	—	—	2.3658
1562409_s_at	—	—	1.52328
230130_at	—	—	2.07003
232833_at	—	—	1.55799
244507_at	—	—	3.42912
1561268_at	—	—	1.54475
1563331_at	—	—	2.23231
224254_x_at	—	—	1.81892
1561346_at	—	—	1.63069
240485_at	—	—	1.61434
238751_at	—	—	2.35739
1561478_at	—	—	1.56036
239706_x_at	—	—	2.03617
240877_x_at	—	—	1.5753
232925_at	—	—	1.58004
1558497_a_at	—	—	2.17382
1555014_x_at	—	—	1.87282
216101_at	—	—	1.99447
240077_at	—	—	1.51092
234550_at	—	—	2.01775
242845_at	—	—	1.60469
1561778_at	—	—	2.41702
242401_x_at	—	—	1.60265
1566695_at	—	—	1.57644
1561123_at	—	—	2.74835
1556491_at	—	—	2.07615
233626_at	—	—	1.68482
1562166_at	—	—	1.63935
242483_at	—	—	1.556
230746_s_at	—	—	3.65236
1561437_at	—	—	1.69604
238512_at	—	—	2.14172
237486_at	—	—	1.64718
215768_at	—	—	2.61093
1561112_at	—	—	2.307
243566_at	—	—	1.54828
242733_at	—	—	2.42057
242171_at	—	—	1.8335
239962_at	—	—	1.94384
1568931_at	—	—	1.68134
239066_at	—	—	1.90013
1558226_a_at	—	—	2.12499
241549_at	—	—	1.54525
1561962_at	—	—	2.00865
1567009_at	—	—	2.33801
238354_x_at	—	—	2.18921
240670_at	—	—	2.07815
220729_at	—	—	2.066
1563414_at	—	—	1.68084
1562491_at	—	—	1.85416
1566805_at	—	—	2.49158
1564819_at	—	—	1.84755
1566848_x_at	—	—	1.63636
244503_at	—	—	2.28069
244736_at	—	—	1.63528
232795_at	—	—	1.88485
235938_at	—	—	2.53577
AFFX-	—	—	3.11913
M27830_3_at
233365_at	—	—	2.76277
234282_at	—	—	2.01659
241667_x_at	—	—	1.7844
243211_at	—	—	1.95149
1557029_at	—	—	1.88354
1564878_at	—	—	1.97934
242419_at	—	—	1.54601
1560049_at	—	—	3.57066
243401_at	—	—	2.22064
1561012_at	—	—	3.09703
1564451_at	—	—	2.88901
1563077_at	—	—	2.08269
244637_at	—	—	1.83073
243694_at	—	—	1.56713
237422_at	—	—	1.60881
1557348_at	—	—	3.30543
1564097_at	—	—	2.32219
240157_at	—	—	1.80217
241222_at	—	—	1.72407
216104_at	—	—	1.72674
1570506_at	—	—	2.29335
1561418_at	—	—	2.52035
1561658_at	—	—	2.77763
243035_at	—	—	1.77962
234179_at	—	—	4.17162
1560760_s_at	—	—	3.16782
231040_at	—	—	1.98115
241387_at	—	—	2.26199
1559724_at	—	—	1.82952
232793_at	—	—	2.69051
216007_at	—	—	1.91365
238414_at	—	—	1.93724
1562464_at	—	—	2.31276
232582_at	—	—	1.64746
244867_at	—	—	2.06707
234652_at	—	—	1.61083
236256_at	—	—	1.97291
232723_at	—	—	2.09444
233043_at	—	—	2.7178
234593_at	—	—	1.86662
233606_at	—	—	3.32752
233668_at	—	—	2.29868
1558019_at	—	—	1.76057
233593_at	—	—	1.64392
1561777_at	—	—	2.12493
241536_at	—	—	2.91919
236962_at	—	—	1.50896
1564654_at	—	—	1.58649
244821_at	—	—	2.35422
231597_x_at	—	—	3.28195
1564807_at	—	—	2.09646
1562137_at	—	—	1.80249
243781_at	—	—	1.69708
244762_at	—	—	2.22632
236276_at	—	—	2.00169
238408_at	—	—	2.44824
1560189_at	—	—	1.70373
1561703_at	—	—	3.73005
233427_x_at	—	—	1.53672
233828_at	—	—	1.6531
234509_at	—	—	2.11383
238411_x_at	—	—	3.42466
244211_at	—	—	1.94329
221174_at	—	—	2.05834
1570125_at	—	—	2.23673
233257_at	—	—	2.01104
233406_at	—	—	2.43719
1562351_at	—	—	1.79422
237353_at	—	—	2.53975
233053_at	—	—	2.26447
243424_at	—	—	2.31946
237962_x_at	—	—	2.49202
1562613_at	—	—	2.67097
1566846_at	—	—	2.74769
231239_at	—	—	1.81363
1562311_at	—	—	1.52118
216496_s_at	—	—	1.69818
1562853_x_at	—	—	1.6179
215801_at	—	—	2.67753
1569809_at	—	—	1.54798
1566469_at	—	—	2.73721
1569858_at	—	—	2.28984
1563561_at	—	—	1.95979
1562828_at	—	—	1.91629
1559434_at	—	—	2.23908
240738_at	—	—	1.68702
1555498_at	—	—	1.8321
1561309_x_at	—	—	1.5393
1566658_at	—	—	1.88495
243828_at	—	—	1.87947
239887_at	—	—	1.96566
231315_at	—	—	2.14126
1556834_at	—	—	5.45617
230959_at	—	—	3.63868
237361_at	—	—	1.89401
241769_at	—	—	2.05931
244112_x_at	—	—	3.84372
1566633_at	—	—	1.96728
216414_at	—	—	1.87759
231598_x_at	—	—	4.5426
237557_at	—	—	2.78756
1566969_at	—	—	1.76339
241654_at	—	—	2.02175
240522_at	—	—	1.83066
1562420_at	—	—	2.41252
234827_at	—	—	1.91205
216214_at	—	—	2.46673
231546_at	—	—	1.98214
1562820_at	—	—	1.67996
233744_at	—	—	1.99092
243902_at	—	—	2.50007
234531_at	—	—	2.08946
1561453_at	—	—	1.68606
237207_at	—	—	2.79429
216595_at	—	—	3.77726
1568611_at	—	—	2.16277
1566716_at	—	—	1.92697
240502_at	—	—	3.31561
238178_at	—	—	1.87863
1562076_at	—	—	2.40574
234581_at	—	—	1.71821
239993_at	—	—	1.6141
1561087_at	—	—	2.91713
239303_at	—	—	1.83918
240788_at	—	—	1.76033
234578_at	—	—	1.93338
241633_x_at	—	—	1.98454
241509_at	—	—	1.88307
1566938_at	—	—	1.62844
241636_x_at	—	—	2.81114
1562169_at	—	—	2.81005
242715_at	—	—	3.98461
1568872_at	—	—	1.7538
1556021_at	—	—	2.6888
241254_at	—	—	2.0837
1564083_at	—	—	2.39374
1564547_x_at	—	—	2.68196
237149_at	—	—	1.70862
233658_at	—	—	1.82247
228732_at	—	—	1.55938
1561450_at	—	—	1.70802
234104_at	—	—	1.61476
1563190_at	—	—	2.07844
241870_at	—	—	1.85956
233448_s_at	—	—	2.276
1561351_at	—	—	2.00141
239970_at	—	—	3.00339
1559149_at	—	—	1.90107
1569944_at	—	—	2.22129
216745_x_at	—	—	1.747
1561199_at	—	—	3.48145
241583_x_at	—	—	1.90832
234228_at	—	—	1.73472
241287_x_at	—	—	1.75873
233853_at	—	—	1.55509
1566970_at	—	—	2.31372
224546_at	—	—	2.91364
1570191_at	—	—	2.76356
215810_x_at	—	—	1.56175
231284_at	—	—	1.94763
239025_at	—	—	1.66351
1566748_at	—	—	2.34934
1569577_x_at	—	—	1.81271
1562083_at	—	—	3.40841
234279_at	—	—	1.75062
236576_at	—	—	1.78665
1562677_at	—	—	1.8276
1560131_at	—	—	2.6117
216858_x_at	—	—	1.5146
1556622_s_at	—	—	2.38938
244258_at	—	—	2.02288
1566426_at	—	—	2.34526
1555365_x_at	—	—	2.6206
1561938_at	—	—	2.13371
1560745_at	—	—	1.79518
234558_at	—	—	1.82691
216764_at	—	—	1.78566
1570155_at	—	—	2.22005
1561411_at	—	—	1.51791
1564070_s_at	—	—	1.64228
233449_at	—	—	1.76305
216286_at	—	—	2.06666
240431_at	—	—	1.86816
244613_at	—	—	1.93862
241628_at	—	—	2.01118
1564134_at	—	—	2.32579
1555187_at	—	—	1.52436
1566863_at	—	—	4.56348
237898_at	—	—	1.51413
1563138_at	—	—	1.72121
238358_x_at	—	—	3.14686
243533_x_at	—	—	2.2352
1558170_at	—	—	2.47388
1564107_at	—	—	2.4479
234773_x_at	—	—	1.85715
1556936_at	—	—	2.0032
1561143_at	—	—	1.53123
242420_at	—	—	2.36834
222325_at	—	—	3.02684
1568878_at	—	—	2.17186
220874_at	—	—	2.17222
222300_at	—	—	2.40438
243262_at	—	—	1.86741
1570176_at	—	—	2.79226
1562111_at	—	—	5.11742
1555364_at	—	—	2.73119
244668_at	—	—	2.52855
233875_at	—	—	2.9792
239959_x_at	—	—	1.60572
215634_at	—	—	2.33921
233908_x_at	—	—	3.48141
237458_at	—	—	1.59163
1560775_at	—	—	2.48169
239095_at	—	—	2.26387
241044_x_at	—	—	2.11189
228731_at	—	—	1.87164
1559360_at	—	—	2.73146
233529_at	—	—	1.63141
238410_x_at	—	—	2.90964
234087_at	—	—	1.80534
241061_at	—	—	2.21281
230859_at	—	—	2.68677
237675_at	—	—	1.54439
234723_x_at	—	—	1.90196
1561364_at	—	—	3.40486
1561953_at	—	—	2.39151
215849_x_at	—	—	1.72743
1566887_x_at	—	—	2.41216
1560517_s_at	—	—	2.16789
220851_at	—	—	2.14141
238392_at	—	—	1.84284
1566609_at	—	—	2.48679
1564610_at	—	—	1.98581
215811_at	—	—	2.30524
1563396_x_at	—	—	1.65546
241584_at	—	—	1.90797
228679_at	—	—	2.37001
241119_at	—	—	2.46146
237933_at	—	—	2.58393
1570624_at	—	—	1.7321
242500_at	—	—	3.04026
216575_at	—	—	4.14875
1566637_at	—	—	2.58398
1566967_at	—	—	2.61969
236389_x_at	—	—	1.73264
1563941_at	—	—	3.17348
244480_at	—	—	3.52279
233372_at	—	—	1.65994
1563115_at	—	—	2.22091
1562642_at	—	—	3.39927
1561473_at	—	—	2.4745
238362_at	—	—	3.29508
1564767_at	—	—	2.62248
241200_x_at	—	—	1.72239
242532_at	—	—	4.03908
238297_at	—	—	2.10442
1570300_at	—	—	2.38986
1562678_at	—	—	2.4369
237700_at	—	—	2.31864
1561212_at	—	—	2.10873
240208_at	—	—	1.73797
238755_at	—	—	2.35516
241883_x_at	—	—	1.67224
243183_at	—	—	2.87008
1559780_at	—	—	1.80843
237454_at	—	—	1.84902
233133_at	—	—	1.86437
237608_at	—	—	1.67052
215643_at	—	—	3.20534
237399_at	—	—	2.50183
1560144_at	—	—	2.65265
220859_at	—	—	2.28617
237049_at	—	—	1.59226
216463_at	—	—	2.33052
1555373_at	—	—	2.40199
1561657_at	—	—	1.67151
240921_at	—	—	1.93703
1569409_x_at	—	—	1.62694
237552_at	—	—	2.25696
238390_at	—	—	3.49633
220878_at	—	—	2.63943
244420_at	—	—	2.17474
1561895_at	—	—	2.59003
233373_at	—	—	2.31025
232712_at	—	—	3.31619
244282_at	—	—	1.64142
215473_at	—	—	1.73547
238274_at	—	—	1.71931
243041_s_at	—	—	3.902
215448_at	—	—	5.09122
241542_at	—	—	2.64253
237480_at	—	—	1.97714
242769_at	—	—	2.65101
240956_at	—	—	2.82294
242840_at	—	—	1.81443
1558048_x_at	—	—	4.43301
241094_at	—	—	1.94022
241945_at	—	—	1.75756
1561242_at	—	—	3.36844
216319_at	—	—	2.21853
1569927_at	—	—	2.86702
234096_at	—	—	1.89863
242645_at	—	—	2.01823
234653_at	—	—	1.92005
1557778_at	—	—	1.77943
1563494_at	—	—	1.61383
215962_at	—	—	3.60791
242652_at	—	—	1.9361
1561795_at	—	—	1.78961
1566498_at	—	—	2.74467
1563963_at	—	—	2.14216
238386_x_at	—	—	1.99773
232817_at	—	—	2.19406
1569759_at	—	—	2.46257
244885_at	—	—	1.90316
242310_at	—	—	1.91359
1569596_at	—	—	3.39789
241183_at	—	—	2.94372
230791_at	—	—	3.79676
1570268_at	—	—	2.16933
1557832_at	—	—	2.09744
1570177_at	—	—	2.4673
234655_at	—	—	1.89067
1561065_at	—	—	1.64279
1562480_at	—	—	3.83981
1557644_at	—	—	2.59969
234690_at	—	—	1.69061
216518_at	—	—	1.90215
234794_at	—	—	2.89785
240186_at	—	—	3.29381
240714_at	—	—	2.18363
217132_at	—	—	1.72792
1561881_at	—	—	2.35965
1562992_at	—	—	2.46132
1568794_at	—	—	2.94005
1568936_a_at	—	—	2.0225
1557665_at	—	—	2.99179
233944_at	—	—	4.72023
240160_x_at	—	—	1.65013
231212_x_at	—	—	2.89146
243756_at	—	—	2.11775
232944_at	—	—	2.10953
243177_at	—	—	3.23332
243442_x_at	—	—	1.9452
243897_at	—	—	1.82779
240825_at	—	—	2.47627
1569664_at	—	—	4.45065
228936_at	—	—	2.51633
1562353_x_at	—	—	1.69798
224237_at	—	—	2.90306
244169_x_at	—	—	3.29173
241632_x_at	—	—	1.59752
228934_x_at	—	—	2.47447
220877_at	—	—	2.67012
228218_at	—	—	2.19026
1561340_at	—	—	1.59817
240988_x_at	—	—	3.81074
234270_at	—	—	2.29525
1570246_at	—	—	2.06463
240904_at	—	—	2.72454
238368_at	—	—	4.76547
240364_at	—	—	2.02402
233209_at	—	—	2.54469
215290_at	—	—	3.33519
233035_at	—	—	1.72582
1562997_a_at	—	—	2.34547
229823_at	—	—	1.67524
244866_at	—	—	2.04538
1563546_at	—	—	6.23891
233906_at	—	—	3.09354
242266_x_at	—	—	2.86831
243466_at	—	—	2.07149
1570623_at	—	—	2.34232
243632_at	—	—	2.62996
240864_at	—	—	3.79135
1569539_at	—	—	5.27322
243489_at	—	—	6.03255
207744_at	—	—	2.86433
237684_at	—	—	2.31226
1570054_at	—	—	1.9518
1557025_a_at	—	—	3.49339
1566115_at	—	—	2.72849
1561069_at	—	—	3.10071
1564840_at	—	—	2.47198
215976_at	—	—	2.16509
1563660_at	—	—	4.23944
216290_x_at	—	—	1.90371
233401_at	—	—	4.47535
233653_at	—	—	1.6959
234015_at	—	—	2.59514
1563026_at	—	—	2.232
210893_at	—	—	2.14379
1563316_at	—	—	4.10042
1554225_a_at	—	—	3.18715
1562071_at	—	—	1.73705
1561754_at	—	—	5.09305
232453_at	—	—	2.65615
243273_at	—	—	2.91387
244300_at	—	—	1.81931
238381_x_at	—	—	1.85034
1561713_at	—	—	3.415
234213_at	—	—	1.5293
231494_at	—	—	4.23233
1560025_at	—	—	3.35764
217617_at	—	—	2.45438
1570152_at	—	—	2.42411
235079_at	—	—	2.25401
1564841_at	—	—	3.20049
237871_x_at	—	—	3.55396
236881_at	—	—	1.86195
233932_at	—	—	3.68719
234137_s_at	—	—	2.30775
1568660_a_at	—	—	3.72993
222339_x_at	—	—	2.47329
1563033_x_at	—	—	6.31222
1559814_at	—	—	2.7905
1556794_at	—	—	2.98574
1560002_at	—	—	1.93616
1561879_at	—	—	2.39371
237596_at	—	—	3.34796
1561513_at	—	—	1.8622
241673_x_at	—	—	2.80804
1561767_at	—	—	2.33844
228827_at	—	—	4.64642
1563332_at	—	—	1.95777
1562800_at	—	—	2.06622
237530_at	—	—	2.59509
244412_at	—	—	2.89052
232538_at	—	—	3.79966
1561543_at	—	—	5.85562
1555926_a_at	—	—	3.01372
238407_at	—	—	2.73065
240112_at	—	—	2.66998
1556989_at	—	—	2.84888
241506_at	—	—	2.4216
1563038_at	—	—	2.87832
237983_at	—	—	3.01582
1563187_at	—	—	3.70922
1559697_a_at	—	—	3.36172
1557762_at	—	—	5.09552
1564631_at	—	—	2.34427
239984_at	—	—	2.4818
1556935_at	—	—	4.49148
233793_at	—	—	3.15092
1561902_at	—	—	3.08744
232935_at	—	—	2.11436
244051_at	—	—	1.55456
1562797_at	—	—	3.02768
1563032_at	—	—	6.99365
242232_at	—	—	3.47935
1563189_at	—	—	4.43695
228502_at	—	—	3.37897
222288_at	—	—	6.71681
1556983_a_at	—	—	3.92804
1558496_at	—	—	5.84122
1566600_at	—	—	1.99013
1557645_at	—	—	2.36718
231227_at	—	—	1.90383
238384_x_at	—	—	3.07283
240331_at	—	—	6.60003
1569818_at	—	—	2.5437
1562084_at	—	—	4.88308
238103_at	—	—	2.96539
1561448_at	—	—	2.80876
240992_at	—	—	1.70856
1568812_at	—	—	2.82372
1562276_at	—	—	4.36824
1564964_at	—	—	5.68325
233330_s_at	—	—	4.92758
233282_at	—	—	3.53402
233331_at	—	—	2.99413
241649_at	—	—	1.98701
1568711_a_at	—	—	1.88935
215736_at	—	—	3.18179
1553498_at	—	—	3.65853
1559696_at	—	—	7.00732
241569_at	—	—	2.15149
241770_x_at	—	—	2.35449
238956_at	—	—	1.77345
234105_at	—	—	2.45775
241026_at	—	—	2.03428
1560533_at	—	—	1.83344
1559336_at	—	—	3.17434
238852_at	—	—	1.85111
244626_at	—	—	3.61861
231687_at	—	—	2.06469
243974_at	—	—	2.23029
1561642_at	—	—	2.17232
233611_at	—	—	2.79902
1569545_at	—	—	2.96746
1569853_at	—	—	2.34808
217569_x_at	—	—	2.20119
244216_at	—	—	3.52052
234057_at	—	—	3.12494
216406_at	—	—	3.25332
241676_x_at	—	—	3.07696
234906_at	—	—	2.94251
1563881_at	—	—	2.97996
237937_x_at	—	—	7.10043
1561856_at	—	—	8.77012
1561529_at	—	—	1.93256
230064_at	—	—	2.99589
1564676_a_at	—	—	3.7315
1562755_at	—	—	4.87812
235494_at	—	—	2.65509
1568871_at	—	—	1.71949
1562873_at	—	—	1.93511
1561214_at	—	—	4.07318
242718_at	—	—	2.56091
1562811_at	—	—	2.21403
241457_at	—	—	2.64311
1564851_at	—	—	2.15494
217085_at	—	—	2.04989
241566_at	—	—	4.90225
1562916_at	—	—	4.01294
1564306_at	—	—	3.50683
243398_at	—	—	4.93521
241247_at	—	—	2.40905
1561213_at	—	—	2.01136
1569810_at	—	—	3.1075
1566622_at	—	—	3.07274
241312_at	—	—	3.10323
241567_at	—	—	2.31223
1560905_at	—	—	5.46696
1560086_at	—	—	3.09926
1556263_s_at	—	—	2.85076
244612_at	—	—	5.78514
1560296_at	—	—	3.17524
231503_at	—	—	3.63922
222342_at	—	—	2.8616
1566638_at	—	—	1.90699
1561926_at	—	—	3.80796
1563087_at	—	—	2.42998
234601_x_at	—	—	1.68879
216728_at	—	—	3.90174
1562610_at	—	—	1.96876
234502_at	—	—	3.82276
242198_at	—	—	2.81983
234235_at	—	—	5.71387
241675_s_at	—	—	6.66189
1555263_at	—	—	2.30475
1566862_at	—	—	3.92941
207731_at	—	—	7.5127
231074_at	—	—	5.19962
237233_at	—	—	4.19082
233279_at	—	—	2.601
237479_at	—	—	6.74027
242802_x_at	—	—	4.62183
234800_at	—	—	1.88126
231091_x_at	—	—	3.87591
241674_s_at	—	—	6.55087

TABLE 9

TIA subtype specific genes: pathways

Ingenuity Canonical		#
Pathways	p-value	Molecules	Molecules

Axonal Guidance	2.48E−03	32	LRRC4C, BDNF, ARHGEF7, UNC5B, PGF, IGF1,
Signaling			SDC2, SRGAP1, EFNA5, ROBO2, SEMA3E,
			EPHA7, ADAM2, SHANK2, PTCH1, PIK3C2G,
			EPHA3, BMP5, ADAM18, GNAS, PLCB4,
			ADAM30, NTRK2, PAK3, ADAM12, NTRK3,
			SEMA6D, GNAO1, EPHA5, PAK7, WNT5A, FZD7
Hepatic Fibrosis/	1.51E−02	13	LEP, EDNRB, IGFBP5, PGF, COL1A2, COL1A1,
Hepatic Stellate Cell			IGF1, PDGFRA, TGFB2, IFNAR1, AGTR1,
Activation			COL3A1, EGFR
Human Embryonic	1.34E−02	13	BDNF, TDGF1, PIK3C2G, BMP5, GNAS, BMPR1B,
Stem Cell			NANOG, NTRK2, NTRK3, PDGFRA, TGFB2,
Pluripotency			FZD7, WNT5A
Neuropathic Pain	9.78E−03	11	GRM5, GRM7, PLCB4, NTRK2, GPR37, BDNF,
Signaling In Dorsal			GRM8, GRM3, PIK3C2G, GRIA2, GRIA3
Horn Neurons
Bladder Cancer	5.08E−03	11	FGF18, MMP26, MMP16, FGF14, FGF12, FGF20,
Signaling			FGF7, PGF, EGFR, MMP19, FGF5
Amyotrophic Lateral	2.02E−02	10	NOS1, CACNA1E, IGF1, HECW1, PIK3C2G,
Sclerosis Signaling			GRIA2, CACNA1C, GRIK2, PGF, GRIA3
Glutamate Receptor	2.74E−03	9	GRM5, GRM7, SLC17A6, GRM8, GRM3, GRIA2,
Signaling			GRIK2, HOMER1, GRIA3
GABA Receptor	2.23E−03	8	SLC6A11, GABBR2, GABRB3, GABRA4,
Signaling			GABRB1, GABBR1, MYO5B, GABRB2
Agrin Interactions at	2.35E−02	8	NRG2, PAK3, ARHGEF7, ERBB4, NRG1, PAK7,
Neuromuscular			ERBB3, EGFR
Junction
Maturity Onset	2.46E−02	4	CACNA1E, ALDOB, FOXA2, CACNA1C
Diabetes of Young
(MODY) Signaling

REFERENCES

1. Johnston S C, Nguyen-Huynh M N, Schwarz M E et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006; 60:301-313
2. Rothwell P M, Buchan A, Johnston S C. Recent advances in management of transient ischaemic attacks and minor ischaemic strokes. Lancet Neurol. 2006; 5:323-331
3. Easton J D, Saver J L, Albers G W et al. Definition and Evaluation of Transient Ischemic Attack A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009; 40:2276-2293
4. Josephson S A, Sidney S, Pham T N et al. Higher ABCD2 score predicts patients most likely to have true transient ischemic attack. Stroke. 2008; 39:3096-3098
5. Zhan X, Ander B P, Jickling G et al. Brief focal cerebral ischemia that simulates transient ischemic attacks in humans regulates gene expression in rat peripheral blood. J Cereb Blood Flow Metab. 2010; 30:110-118
6. Zhan X, Kim C, Sharp F R. Very brief focal ischemia simulating transient ischemic attacks (TIAs) can injure brain and induce Hsp70 protein. Brain Res. 2008; 1234:183-197
7. Arenillas J F, Alvarez-Sabin J, Molina C A et al. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke. 2003; 34:2463-2468
8. Elneihoum A M, Falke P, Axelsson L et al. Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke. 1996; 27:1734-1738
9. Ross A M, Hurn P, Perrin N et al. Evidence of the peripheral inflammatory response in patients with transient ischemic attack. J Stroke Cerebrovasc Dis. 2007; 16:203-207
10. Castillo J, Alvarez-Sabin J, Martinez-Vila E et al. Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study. J Neurol. 2009; 256:217-224
11. Nambi V, Hoogeveen R C, Chambless L et al. Lipoprotein-associated phospholipase A2 and high-sensitivity C-reactive protein improve the stratification of ischemic stroke risk in the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2009; 40:376-381
12. Cucchiara B L, Messe S R, Sansing L et al. Lipoprotein-associated phospholipase A2 and C-reactive protein for risk-stratification of patients with TIA. Stroke. 2009; 40:2332-2336
13. Rothwell P M, Howard S C, Power D A et al. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke. Stroke. 2004; 35:2300-2305
14. Woodward M, Lowe G D, Campbell D J et al. Associations of inflammatory and hemostatic variables with the risk of recurrent stroke. Stroke. 2005; 36:2143-2147
15. Kang D W, Yoo S H, Chun S et al. Inflammatory and hemostatic biomarkers associated with early recurrent ischemic lesions in acute ischemic stroke. Stroke. 2009; 40:1653-1658
16. Moore D F, Li H, Jeffries N et al. Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation. Circulation. 2005; 111:212-221
17. Tang Y, Xu H, Du X et al. Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab. 2006; 26:1089-1102
18. Xu H, Tang Y, Liu D Z et al. Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke. J Cereb Blood Flow Metab. 2008; 28:1320-1328
19. Giles M F, Rothwell P M. Systematic review and pooled analysis of published and unpublished validations of the ABCD and ABCD2 transient ischemic attack risk scores. Stroke. 2010; 41:667-673
20. Cucchiara B L, Messe S R, Sansing L et al. D-dimer, magnetic resonance imaging diffusion-weighted imaging, and ABCD2 score for transient ischemic attack risk stratification. J Stroke Cerebrovasc Dis. 2009; 18:367-373
21. Andersohn F, Waring M, Garbe E. Risk of ischemic stroke in patients with Crohn's disease: A population-based nested case-control study. Inflamm Bowel Dis. 2009
22. Freilinger T, Riedel E, Holtmannspotter M et al. Ischemic stroke and peripheral arterial thromboembolism in a patient with Crohn's disease: a case presentation. J Neurol Sci. 2008; 266:177-179
23. Karacostas D, Mavromatis J, Artemis K, Milonas I. Hemorrhagic cerebral infarct and ulcerative colitis. A case report. Funct Neurol. 1991; 6:181-184
24. Schneiderman J H, Sharpe J A, Sutton D M. Cerebral and retinal vascular complications of inflammatory bowel disease. Ann Neurol. 1979; 5:331-337
25. Beck J D, Offenbacher S. Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J. Periodontol. 2005; 76:2089-2100
26. Beck J, Garcia R, Heiss G et al. Periodontal disease and cardiovascular disease. J. Periodontol. 1996; 67:1123-1137
27. Elter J R, Offenbacher S, Toole J F, Beck J D. Relationship of periodontal disease and edentulism to stroke/TIA. J Dent Res. 2003; 82:998-1001
28. Grau A J, Becher H, Ziegler C M et al. Periodontal disease as a risk factor for ischemic stroke. Stroke. 2004; 35:496-501
29. Grau A J. Infection, inflammation, and cerebrovascular ischemia. Neurology. 1997; 49:547-51
30. Dourado D F, Fernandes P A, Ramos M J. Mammalian cytosolic glutathione transferases. Curr Protein Pept Sci. 2008; 9:325-337

It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, sequence accession numbers, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

Claims

1. A method for diagnosing a transient ischemic attack (TIA) or a predisposition for experiencing TIA, the method comprising: determining a level of expression of a plurality of TIA-associated biomarkers in a biological sample from a patient, wherein an increase or decrease of the level of expression compared to a control indicates that the patient has suffered or is at risk of experiencing TIA, wherein the plurality of TIA-associated biomarkers is selected from the biomarkers set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and 9.

2-5. (canceled)

6. The method of claim 1, wherein an increased expression level of one or more TIA-associated biomarkers selected from the group consisting of DKFZP434B061, FAM55D, F1130375, IGFBP5, LTBR and SCN2A indicates that the patient has suffered or is at risk of experiencing TIA.

7. The method of claim 1, wherein an increased expression level of one or more TIA-associated biomarkers selected from the group consisting of GABRB2, ELAVL3, TWIST1, DPPA4, DKFZP434P211, DLX6, ZNF479, ASTN2, SNX31, ALS2CR11, LOC440345 indicates that the patient has suffered or is at risk of experiencing TIA.

8. (canceled)

9. The method of claim 1, wherein a decreased expression level of one or more TIA-associated biomarkers selected from the group consisting of ATG9B, DIP2C, EDAR, GSTM1, GUSBL2, SMURF2, ZNF512B indicates that the patient has suffered or is at risk of experiencing TIA.

10. The method of claim 1, wherein a decreased expression level of one or more TIA-associated biomarkers selected from the group consisting of NBPF10///RP11-9412.2, SFXN1, SPIN3, UNC84A, OLFM2, PPM1K, P2RY10, ZNF512B, MORF4L2, GIGYF2, ERAP2, SLFN13, LOC401431, MED6, BAIAP2L1///LOC100128461, LNPEP, MBNL1, NOS3, MCF2L, KIAA1659, SCAMPS, LOC648921, ANAPC5, SPON1, FUS, GPR22, GAL3ST4, METTL3, LOC100131096, FAAH2, SMURF2, SNRPN, FBLN7, GLS, G3BP1, RCAN3, EPHX2, DIP2C, CCDC141, CLTC, FOSB, CACNA1I, UNQ6228, ATG9B, AK5, SPIN3, RBM14, SNRPN, MAN1C1, HELLS, EDAR, SLC3A1, ZNF519, LOC100130070///LOC100130775///LOC100131787///LOC100131905///LOC100132291///LOC100132488///RPS27, ZC3H12B, IQGAP2, SOX8, WHDC1L2, TNPO1, TNFRSF21, TSHZ2, DMRTC1///DMRTC1B, GSTM1, GSTM2, PNMA6A, CAND1, CCND3, GSTM1, GUSBL2 indicates that the patient has suffered or is at risk of experiencing TIA.

11-32. (canceled)

33. The method of claim 1, wherein the level of expression of the biomarker is determined at the transcriptional level.

34. The method of claim 1, wherein the level of expression is determined by detecting hybridization of a TIA-associated gene probe to gene transcripts of the biomarkers in the biological sample.

35. The method of claim 34, wherein the hybridization step is performed on a nucleic acid microarray chip.

36. The method of claim 34, wherein the hybridization step is performed in a microfluidics assay plate.

37. The method of claim 1, wherein the level of expression is determined by amplification of gene transcripts of the biomarkers.

38. The method of claim 37, wherein the amplification reaction is a polymerase chain reaction (PCR).

39. (canceled)

40. The method of claim 1, wherein the level of expression of at least 15 biomarkers is determined.

41. The method of claim 1, further comprising the step of obtaining a biological sample.

42. The method of claim 1, wherein the biological sample is blood, serum or plasma.

43. The method of claim 1, wherein the control is the expression level of a plurality of stably expressed endogenous reference biomarkers.

44. The method of claim 43, wherein the one or more endogenous reference biomarkers is selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4 KB, CRTC1, HADHA, MAP1LC3B, KAT5, CDC2L1///CDC2L2, GTSE1, CDC2L1///CDC2L2, TCF25, CHP, LRRC40, hCG 2003956///LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHC5, C9orf23, LRRC45, NACC1, LOC100133445///LOCI-15110 and PEX16

45. The method of claim 1, wherein the control is the expression level of the same biomarker in a healthy individual.

46. The method of claim 1, wherein the control is a threshold level of expression representative of a population of healthy individuals.

47. The method of claim 1, further comprising the step of providing an appropriate treatment or prevention regime for TIA to the patient.

48. A solid support comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 2, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5A, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5B, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5C, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5D, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 7, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 8 and a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 9.

49. The solid support of claim 48, comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of GUSBL2, GSTM1, F1130375, SCN2A, DKFZP434B061, EDAR, ATG9B, DIP2C, LTBR, SMURF2, FAM55D, IGFBP5, and ZNF512B.

50-60. (canceled)

61. The solid support of claim 48, wherein the solid support is a microarray.