Accurate Quantification of Functional Analogy among Close Homologs 英文参考文献.docVIP

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Accurate Quantification of Functional Analogy among Close Homologs 英文参考文献.doc

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Accurate Quantification of Functional Analogy among Close Homologs 英文参考文献

AccurateQuantificationofFunctionalAnalogyamong CloseHomologs MariaD.Chikina1,OlgaG.Troyanskaya2,3* 1Department ofMolecular Biology, Princeton University, Princeton, New Jersey, United States ofAmerica, 2Lewis-Sigler Institute for Integrative Genomics, Princeton University,Princeton,NewJersey,UnitedStatesofAmerica,3DepartmentofComputerScience,PrincetonUniversity,Princeton,NewJersey,UnitedStatesofAmerica Abstract Correctlyevaluatingfunctionalsimilaritiesamonghomologousproteinsisnecessaryforaccuratetransferofexperimental knowledgefromoneorganismtoanother,andisofparticularimportanceforthedevelopmentofanimalmodelsofhuman disease.Whilethefactthatsequencesimilarityimpliesfunctionalsimilarityisafundamentalparadigmofmolecularbiology, sequencecomparisondoesnotdirectlyassesstheextenttowhichtwoproteinsparticipateinthesamebiologicalprocesses, andhaslimitedutilityforanalyzingfamilieswithseveralparologousmembers.Nevertheless,weshowthatitispossibleto provideacross-organismfunctionalsimilaritymeasureinanunbiasedwaythroughtheexclusiveuseofhigh-throughput gene-expressiondata.Ourmethodologyisbasedonprobabilisticcross-speciesmappingoffunctionallyanalogousproteins basedonBayesianintegrativeanalysisofgeneexpressioncompendia.Wedemonstratethatevenamongcloselyrelated genes,ourmethodisabletopredictfunctionallyanalogoushomologpairsbetterthanrelyingonsequencecomparison alone. We also demonstrate that the landscape of functional similarity is often complex and that definitive ‘‘functional orthologs’’donotalwaysexist.Eveninthesecases,ourmethodandtheonlineinterfaceweprovidearedesignedtoallow detailedexplorationofsourcesofinferredfunctionalsimilaritythatcanbeevaluatedbytheuser. Citation: Chikina MD, Troyanskaya OG (2011) Accurate Quantification of Functional Analogy among Close Homologs. PLoS Comput Biol 7(2): e1001074. doi:10.1371/journal.pcbi.1001074 Editor:RichardBonneau,NewYorkUniversity,UnitedStatesofAmerica ReceivedJune4,2010;AcceptedJanuary2,2011;PublishedFebruary3,2011 Copyright:?2011Chik