蛋白質(zhì)相互作用生物信息學(xué)高友鶴中國(guó)醫(yī)學(xué)科學(xué)院基礎(chǔ)醫(yī)學(xué)研究所1/35蛋白質(zhì)相互作用生物信息學(xué)試驗(yàn)數(shù)據(jù)蛋白質(zhì)相互作用數(shù)據(jù)庫(kù)高通量試驗(yàn)數(shù)據(jù)驗(yàn)證蛋白質(zhì)相互作用網(wǎng)絡(luò)計(jì)算預(yù)測(cè)蛋白質(zhì)相互作用2/35試驗(yàn)數(shù)據(jù)

蛋白質(zhì)相互作用知識(shí)起源于試驗(yàn)。高通量地應(yīng)用傳統(tǒng)試驗(yàn)方法獲取大量相互作用信息。高通量數(shù)據(jù)需要驗(yàn)證。3/35高通量試驗(yàn)方法CurrOpinStructBiol,13:3774/35Yeasttwo-hybridassay

Benefits:invivo.Don’tneedpureproteins.Don’tneedAb.Drawbacks:only

twoproteinsaretestedatatime(nocooperativebinding);ittakesplaceinthenucleus,somanyproteinsarenotintheirnativecompartment;anditpredictspossibleinteractions,butisunrelatedtothephysiologicalsetting.

5/35Massspectrometryofpurifiedcomplexes

Benefits:severalmembersofacomplexcanbe

tagged,givinganinternalcheckforconsistency;anditdetects

realcomplexesinphysiologicalsettings.Drawbacks:itmight

misssomecomplexesthatarenotpresentunderthegivenconditions;taggingmaydisturbcomplexformation;andlooselyassociatedcomponentsmaybewashedoffduringpurification.

6/35CorrelatedmRNAexpressionBenefits:itisaninvivotechnique,albeitanindirectone;andithasmuchbroadercoverageofcellularconditionsthanothermethods.Drawbacks:itisapowerfulmethodfordiscriminatingcellstatesordiseaseoutcomes,butisarelativelyinaccuratepredictorofdirectphysicalinteraction;anditisverysensitivetoparameterchoicesandclusteringmethodsduringanalysis.7/35Geneticinteractions(syntheticlethality).Benefits:itisaninvivotechnique,albeitanindirectone;anditisamenableto

unbiasedgenome-widescreens.Drawbacks:notnecessarilyphysicalinteractions8/35蛋白質(zhì)相互作用生物信息學(xué)試驗(yàn)數(shù)據(jù)蛋白質(zhì)相互作用數(shù)據(jù)庫(kù)高通量試驗(yàn)數(shù)據(jù)驗(yàn)證蛋白質(zhì)相互作用網(wǎng)絡(luò)計(jì)算預(yù)測(cè)蛋白質(zhì)相互作用9/35蛋白質(zhì)相互作用數(shù)據(jù)庫(kù)

CurrOpinStructBiol,13:37710/35THEDIPDATABASEDatabaseofInteractingProteinsTheDIPdatabasecatalogsexperimentallydeterminedinteractionsbetweenproteins.11/35DIP相互作用表示

NucleicAcidsResearch,,28,289－29112/35DIP數(shù)據(jù)庫(kù)結(jié)構(gòu)

NucleicAcidsResearch,,28,289－29113/35BIND：theBiomolecularInteractionNetworkDatabaseNucleicAcidsResearch,,29,242-24514/35蛋白質(zhì)相互作用生物信息學(xué)試驗(yàn)數(shù)據(jù)蛋白質(zhì)相互作用數(shù)據(jù)庫(kù)高通量試驗(yàn)數(shù)據(jù)驗(yàn)證蛋白質(zhì)相互作用網(wǎng)絡(luò)計(jì)算預(yù)測(cè)蛋白質(zhì)相互作用15/35高通量試驗(yàn)數(shù)據(jù)需要驗(yàn)證

CurrOpinStructBiol,13:37716/35與可信數(shù)據(jù)相比CurrOpinStructBiol,13:37717/35ExpressionProfileReliabilityEPRIndexExpressionProfileReliabilityIndex(EPRIndex)evaluatesthequalityofalarge-scaleprotein-proteininteractiondatasetsbycomparingtheexpressionprofileoftheinteractingdatasetwiththatofthehigh-qualitysubsetoftheDIPdatabase.18/35高通量數(shù)據(jù)相互比CurrOpinStructBiol,13:37719/35ParalogousVerificationMethodPVMScoreTheParalogousVerification(PVM)methodjudgesaninteractionprobableiftheputativelyinteractingpairhasparalogsthatalsointeract.20/35DomainPairVerificationDPVScoreTheDomainPairVerification(DPV)methodjudgesaninteractionprobableifpotentialdomain-domaininteractionsbetweenthepairaredeemedprobable.21/35CorrelationdistanceNatureBiotechnology

,22,7822/35蛋白質(zhì)相互作用網(wǎng)絡(luò)Nature,411,41-4223/35相互作用網(wǎng)絡(luò)用途Themosthighlyconnectedproteinsinthecellarethemostimportantforitssurvival.

Nature,411,41-4224/35蛋白質(zhì)相互作用生物信息學(xué)試驗(yàn)數(shù)據(jù)蛋白質(zhì)相互作用數(shù)據(jù)庫(kù)高通量試驗(yàn)數(shù)據(jù)驗(yàn)證蛋白質(zhì)相互作用網(wǎng)絡(luò)計(jì)算預(yù)測(cè)蛋白質(zhì)相互作用25/35計(jì)算預(yù)測(cè)蛋白質(zhì)相互作用CurrOpinStructBiol,13:37726/35DockingNeed3DStructuresCAPRI:CriticalAssessmentofPredictedInteractions,acommunity-wideexperimentforassessingthepredictivepoweroftheseprocedures.27/35ProteinFusionBasedon:Somepairsofinteractingproteinsencodedinseparategenesinoneorganismarefusedtoproducesinglehomologousproteinsinotherorganism.CompareE.Coliwithothergenomes:6,809putativeprotein-proteininteractionsMarcotteEMScience285,751(1999)Compareyeastwithothers:45,502putativeinteractionsEnrightAJNature402,86(1999)28/35GeneClusteringBasedon:Functionalcouplinggenesareinconservedgeneclustersindifferentgenomes.29/35GeneClusteringOverbeekRPNAS96,2896(1999)30/35OverbeekRPNAS96,2896(1999)31/35PhylogeneticprofilePNAS(1999)96,4285-428832/35ACombinedExperimentalandComputationalStrategy1)Screenrandompeptidelibrariesbyphagedisplaytodefinetheconsensussequencesforpreferredligandsthatbindtoeach

peptiderecognitionmodule.2)Onthebasisoftheseconsensussequences,computationallyderiveaprotein-proteininteractionnetworkthatlinkseach

peptiderecognitionmoduletoproteinscontainingapreferred

peptideligand.Science295,32133/353)Experimentallyderiveaprotein-proteininteractionnetworkbytestingeachpeptiderecognitionmoduleforassociation

toeachproteinoftheinferredproteomeintheyeasttwo-hybrid

system.4