RIDDLE reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network 英文参考文献.docVIP

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RIDDLE reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network 英文参考文献.doc

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RIDDLE reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network 英文参考文献

Wangetal.GenomeBiology2012,13:R125 /2012/13/12/R125 METHOD OpenAccess RIDDLE:reflectivediffusionandlocalextension revealfunctionalassociationsforunannotated genesetsviaproximityinagenenetwork PeggyIWang1,2?,SohyunHwang3?,RodneyPKincaid2,4,ChristopherSSullivan2,4,InsukLee3*and EdwardMMarcotte2,5* Abstract Thegrowingavailabilityoflarge-scalefunctionalnetworkshaspromotedthedevelopmentofmanysuccessful techniquesforpredictingfunctionsofgenes.Hereweextendthesenetwork-basedprinciplesandtechniquesto functionallycharacterizewholesetsofgenes.WepresentRIDDLE(ReflectiveDiffusionandLocalExtension),which useswelldevelopedguilt-by-associationprinciplesuponahumangenenetworktoidentifyassociationsofgene sets.RIDDLEisparticularlyadeptatcharacterizingsetswithnoannotations,amajorchallengewheremost traditionalsetanalysesfail.Notably,RIDDLEfoundmicroRNA-450atobestronglyimplicatedinoculardiseasesand development.A/RIDDLE. Background suchas[2,3],genesarefirstrankedbysomesuitablemea- Inthemodern ageofhigh-throughput genetic studies, sure,forexample,differentialexpressionacrosstwodiffer- functionalenrichmentanalysesremainavitalapproachto entconditions,andpossibleenrichmentisfoundnearthe analyzingdata.Microarray,massspectrometry,genome- extremesofthelist.Rank-basedmethodsareusuallyhighly wideassociation, andother genome-level studies com- specializedforgeneexpressionarrayanalysis.Bothoverlap monly produce query gene sets -gene sets ofinterest, andrank-basedmethodsrequirethequeriedgenestobe oftencontaining manyuncharacterized members, from sufficientlyannotated. whichcoherentbiologicalmodulesneedtobeidentified. Insomemorerecentlydevelopedlocal-networkmeth- There exist many methods that attempt to discover ods(Figure1c),aquerysetiscomparedagainstthegenes known biological functions involved with aquery set, andinternalinteractionsofaknownfunctionalpathway. mostofwhichfallunderoneofthreebroadcategories: These interactions may bevisualized asamapornet- overlap-based,rank-based