Gene Set Enrichment in eQTL Data Identifies Novel Annotations and Pathway Regulators 英文参考文献.docVIP

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Gene Set Enrichment in eQTL Data Identifies Novel Annotations and Pathway Regulators 英文参考文献.doc

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Gene Set Enrichment in eQTL Data Identifies Novel Annotations and Pathway Regulators 英文参考文献

GeneSetEnrichmentineQTLDataIdentifiesNovel AnnotationsandPathwayRegulators ChunleiWu1,DavidL.Delano1,NicoMitro2,StephenV.Su1,JeffJanes1,PhillipMcClurg1 ,Serge Batalov1,GenevieveL.Welch1,JieZhang1,AnthonyP.Orth1,JohnR.Walker1,RichardJ.Glynne1, MichaelP.Cooke1,JosephS.Takahashi3,4,KazuhiroShimomura3,4,AkiraKohsaka3,5,JosephBass3,5,6 EnriqueSaez2,TimWiltshire1¤,AndrewI.Su1* , 1GenomicsInstituteoftheNovartisResearchFoundation,SanDiego,California,UnitedStatesofAmerica,2DepartmentofChemicalPhysiology,TheScrippsResearch Institute,LaJolla,California,UnitedStatesofAmerica,3DepartmentofNeurobiologyandPhysiology,NorthwesternUniversity,Evanston,Illinois,UnitedStatesofAmerica, 4Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois, United States of America, 5Evanston Northwestern Healthcare Research Institute, Evanston,Illinois,UnitedStatesofAmerica,6DepartmentofMedicine,FeinbergSchoolofMedicine,NorthwesternUniversity,Evanston,Illinois,UnitedStatesofAmerica Abstract Genome-widegeneexpressionprofilinghasbeenextensivelyusedtogeneratebiologicalhypothesesbasedondifferential expression. Recently, many studies have used microarrays to measure gene expression levels across genetic mapping populations.Thesegeneexpressionphenotypeshavebeenusedforgenome-wideassociationanalyses,ananalysisreferred toasexpressionQTL(eQTL)mapping.Here,eQTLanalysiswasperformedinadiposetissuefrom28inbredstrainsofmice. Wefocusedouranalysison‘‘trans-eQTLbands’’,definedasinstancesinwhichtheexpressionpatternsofmanygeneswere allassociatedtoacommongeneticlocus.Genescomprisingtrans-eQTLbandswerescreenedforenrichmentsinfunctional genesetsrepresentingknownbiologicalpathways,andgeneslocatedatassociatedtrans-eQTLbandlociwereconsidered candidate transcriptional modulators. We demonstrate that these patterns were enriched for previously characterized relationshipsbetweenknownupstreamtranscriptionalregulatorsandtheirdownstreamtargetgenes.Moreover,weused this strategy to identify both novel regulators