BIOMARKERS FOR DIAGNOSIS OF TRANSIENT ISCHEMIC ATTACKS

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

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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

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

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 Tm is 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 Tm, 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 Fold- Fold- Change Change (TIA vs. RefSeq (TIA vs. Control) Probeset ID Gene Symbol Gene Title Transcript ID Control) (Description) 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 KD of 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 ABCD2 score≧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 ABCD2 score (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, ABCD2 score (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 ABCD2 score (±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, ABCD2 score, 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 — 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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

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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.

Patent History
Publication number: 20120015904
Type: Application
Filed: Jul 14, 2011
Publication Date: Jan 19, 2012
Applicant: Regents of the University of California (Oakland, CA)
Inventors: Frank SHARP (Davis, CA), Xinhua ZHAN (Vacaville, CA), Glen C. JICKLING (Sacramento, CA), S. Claiborne JOHNSTON (San Francisco, CA)
Application Number: 13/182,630