Computational Proteomics of Protein Complexes -

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1、ComputationalProteomicsofProteinComplexesMarkBGersteinYaleU1TheInteractome:theNext‘omicStepInteractomeProteomeTranscriptomeGenome2Thepopularityofinteractomeinformation3ComputationalProteomicsofComplexesInteractionsprovideasystematicwayofdefiningproteinfunctiononagenom

2、icscaleKnowncomplexesprovideabenchmarktovalidateandintegrategenome-wideinteractionexperiments,providingamoreaccurateinteractomeKnowncomplexesprovideafocusfortheintergrationof(non-interaction)genomicinformation–e.g.expressiondataExtrapolatingfromknowncomplexes,onecanpred

3、ictproteincomplexesonagenome-scaleviaintegratingexperimentalinteractionsandnon-interactioninformation(combining#1and#2)4CircumscribingProteinFunctionintermsofInteractions5UnderstandingProteinFunctiononaGenomicScale250of650knownonchr.22[Dunhametal.]>>30K+ProteinsinEntir

4、eHumanGenome(alt.splicing).……~6506IssuesindefiningproteinfunctiononagenomicscaleMulti-functionality:2functions/protein(also2proteins/function)RoleConflation:molecular,cellular,phenotypicFunterms…butdotheyscale?StarrynightSarah(affectsfemalefertility);Sonic;Darkenerof

5、apricot&suppressorofwhiteapricot;Redtape,gridlock,roadblock(whenmutatedblocktransportalongaxons);ROPvsROM("RegulatorofCopyNumber"orRNA-I-II-complex-binding-protein)Fornow,definableaspectsoffunction:interactions,location,enzymaticrxn.[Babbit]7Ontologiesforfunction:Networ

6、ks,Hierarchies,DAGs8Ontologiesforfunction:InteractionvectorsLanetal.IEEE(2002)&COSB(2003)9ValidatingandIntegratingGenomicProtein-ProteinInteractionDatasetswithKnownComplexes10ProteininteractiondataDatabases(BIND,DIP,MIPSetc.)literatureHigh-throughputdatasetsinvivopul

7、ldownyeasttwo-hybridComputationalpredictionsTangentialgenomicdataExpressiondataPhenotypicdataLocalizationData11CombininginteractiondataHigh-throughputdataislessreliablethanmorecareful,smallerscaleexperimentsOrthogonaldatasetsCombiningdataincreasesaccuracycoverageHowtodo

8、thisinaquantitativeway?Howtoweightthedifferentdatasources?Generalclassificationproblem(machinelearning)Bayesia