Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data 英文参考文献.docVIP

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Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data 英文参考文献.doc

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Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data 英文参考文献

FunctionalMapsofProteinComplexesfromQuantitative GeneticInteractionData SouravBandyopadhyay1,2,RyanKelley1,2,NevanJ.Krogan3,TreyIdeker1,2* 1PrograminBioinformatics,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2DepartmentofBioengineering,UniversityofCaliforniaSan Diego,LaJolla,California,UnitedStatesofAmerica,3DepartmentofCellularandMolecularPharmacology,UniversityofCaliforniaSanFrancisco,SanFrancisco,California, UnitedStatesofAmerica Abstract Recently,anumberofadvancedscreeningtechnologieshaveallowedforthecomprehensivequantificationofaggravating andalleviatinggeneticinteractionsamonggenepairs.Inparallel,TAP-MSstudies(tandemaffinitypurificationfollowedby massspectroscopy)havebeensuccessfulatidentifyingphysicalproteininteractionsthatcanindicateproteinsparticipating inthesamemolecularcomplex.Here,weproposeamethodforthejointlearningofproteincomplexesandtheirfunctional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, wedemonstrate that this methodis .50% more accurate at identifyingfunctionally related proteinpairs than previousapproaches.Applicationtogenesinvolvedinyeastchromosomeorganizationidentifiesafunctionalmapof91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly,wefindthatcomplexesthatareenrichedforaggravatinggeneticinteractions(i.e.,syntheticlethality)aremore likelytocontainessentialgenes,linkingeachoftheseinteractionstoanunderlyingmechanism.Theseresultsdemonstrate theimportanceofbothlarge-scalegeneticandphysicalinteractiondatainmappingpathwayarchitectureandfunction. Citation:BandyopadhyayS,KelleyR,KroganNJ,IdekerT(2008)FunctionalMapsofProteinComplexesfromQuantitativeGeneticInteractionData.PLoSComput Biol4(4):e1000065.doi:10.1371/journal.pcbi.1000065 Editor:AlpanRaval,KeckGraduateInstituteofAppliedLifeSciences,UnitedStatesofAmerica ReceivedOctober26,2007;AcceptedMarch19,2008;Publishe