BridgingtheGapFromIndividualGenestoSystemsBiologyNetworkBridgingtheGapFromIndividualGenestoSystemsBiologyNetwork——(randomPN(scale-freeKKKBarabasiAL,OltvaiZ.Naturereviewsgenetics,(randomPN(scale-freeKKKBarabasiAL,OltvaiZ.Naturereviewsgenetics,2004,5(2):101-Steve·(weightedgeneSteve·(weightedgene/(scale-/(scale-Let’sGotoConstructaScale-freeBiologyNetworkStepbyStepLet’sGotoConstructaScale-freeBiologyNetworkStepbyStep(unweighted(weightedZhangB,HorvathS.Statisticalapplicationsingenetics(unweighted(weightedZhangB,HorvathS.Statisticalapplicationsingeneticsandmolecularbiology,2005,4(1):nPearsoncorrelationSpearman’scorrelationBiweightmidcorrelation1????? ??????=n?16σ??=1?2???????????=9?????????????????=9??????2nPearsoncorrelationSpearman’scorrelationBiweightmidcorrelation1????? ??????=n?16σ??=1?2???????????=9?????????????????=9??????22=1?1? 1???1 22(????????????????22(??? ?Sij=(hardthresholdHorvathS,DongJ.PLoScomputbiol,(hardthresholdHorvathS,DongJ.PLoScomputbiol,2008,4(8):(softAlbertR.Journalofcellscience,2005,(softAlbertR.Journalofcellscience,2005,118(21):4947-(topological????=????==(topological????=????==+=????,+1?=1?YipAM,HorvathS.BMCbioinformatics,2007,8(1):22.LiA,HorvathS.Bioinformatics,2007,23(2):222-power(s,β=YipAM,HorvathS.power(s,β=YipAM,HorvathS.BMCbioinformatics,2007,8(1):22.LiA,HorvathS.Bioinformatics,2007,23(2):222-TOM-baseddissimilarity12??c=??????????????0/2TOM-baseddissimilarity12??c=??????????????0/2?????0,2LangfelderaP,ZhangbB,HorvathaS.DynamicTreeCut:in-depthdescription,testsandapplications[J].November,2007,22:2007.βA(co-expression)networkisanundirected,weightednetworkwithnodescorrespondingβA(co-expression)networkisanundirected,weightednetworkwithnodescorrespondinggenes(orproteins,metabolitesandsoon)andedgesbasedupongene-geneco-expressionlevels.Toevaluateco-expressionlevelsbetweengenes,Pearsoncorrelationsaretakenandthenweightedbyraisingtheirabsolutevaluetoapowerβinadjacencyfunction).weightingemphasizesstrongcorrelationsattheexpenseofweakMillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.01(Weighted)adjacencymatrixisasymmetricmatrixwhoseoffdiagonalelementsliebetween0and1.Theadjacenciesmeasuretheconnectionstrength01(Weighted)adjacencymatrixisasymmetricmatrixwhoseoffdiagonalelementsliebetween0and1.Theadjacenciesmeasuretheconnectionstrengthbetweenpairsofnodes.Incorrelationnetworks,theadjacencybetweentwogenesisapowerofthePearsoncorrelationbetweentheirexpressionTO(topologicaloverlap)isaquantitydescribinggenepairsimilaritybycomparingweightedcorrelationofthesegeneswithallothergenesintheMillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.Amoduleisagroupofgeneswithstrongsharingofco-expressionrelationshipsasmeasuredbyhighTO.ModulesareidentifiedviaAmoduleisagroupofgeneswithstrongsharingofco-expressionrelationshipsasmeasuredbyhighTO.Modulesareidentifiedviahierarchicalclusteringusingameasureofdissimilarity(i.e.,1?TO).Genesinamoduleshowmuchhigherco-expressionwitheachother(eitherpositiveornegative)thanwithgenesoutsidetheTheME(moduleeigengene)isthefirstprincipalcomponentofamodule.TheMEsummarizesthecharacteristicexpressionpatternofamodule.MillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.MM(ModuleMembership,alsoknownaseigengene-basedconnectivitykME)isthePearsoncorrelationbetweentheexpressionlevelofagivengeneandagivenME.ThisquantitydescribestheextenttoMM(ModuleMembership,alsoknownaseigengene-basedconnectivitykME)isthePearsoncorrelationbetweentheexpressionlevelofagivengeneandagivenME.Thisquantitydescribestheextenttowhichagene“belongs”toamodule,andisusedinthefinalmoduleMillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.IntramodularconnectivityisameasurementofnetworkpositionthatIntramodularconnectivityisameasurementofnetworkpositionthatreflectsconnectedagivengeneiswithrespecttothegenesofaparticularmodule.Thehigherthekin,themorecentralageneistothenetwork.(Overall)connectivityisthesumofconnectionstrengths(adjacencymatrixvalues)withallothernetworkgenes.TheconnectivitymeasureshowcorrelatedageneiswithallothergenesinaMillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.Ahubisanyhighlyconnectedgene.AhubcanbecharacterizedbyhighAhubisanyhighlyconnectedgene.AhubcanbecharacterizedbyhighMM,intramodularconnectivity,orastrongpresenceinnetworkModulecharacterizationisashortdescriptivetermcharacterizinggenesinamodulebasedonGO,KEGGorIPAannotation,moduleoverlapwithexperimentallyderivedgenelists,andmoduleoverlapwithmodulespreviouslycharacterizedandMillerJA,HorvathS,GeschwindDH.ProceedingsoftheNationalAcademyofSciences,2010,107(28):12698-12703.(Individual/Convergent/divergentmodulesandnodesConvergent/divergentconnectionpropertiesLangfelderP,Horvath(Individual/Convergent/divergentmodulesandnodesConvergent/divergentconnectionpropertiesLangfelderP,HorvathS.BMCsystemsbiology,2007,1(1):2Moduleoverlapisthenumberofcommongenesbetween2Moduleoverlapisthenumberofcommongenesbetweenonemodule(orlist)anddifferentmodule(orlist).Thesignificanceofmoduleoverlapcanbemeasuredusingthehypergeometrictest.Modulepreservationisanyofanumberofteststhatmeasurehowwellcharacteristicsofmoduleinonenetworkarereproducedinanother(