From Knockouts to Networks Establishing Direct Cause-Effect Relationships through Graph Analysis 英文参考文献.docVIP

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From Knockouts to Networks Establishing Direct Cause-Effect Relationships through Graph Analysis 英文参考文献.doc

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From Knockouts to Networks Establishing Direct Cause-Effect Relationships through Graph Analysis 英文参考文献

FromKnockoutstoNetworks:EstablishingDirectCause- EffectRelationshipsthroughGraphAnalysis AndreaPinna,NicolaSoranzo,AlbertodelaFuente* CenterforAdvancedStudies,ResearchandDevelopment(CRS4)Bioinformatica,Pula,Italy Abstract Background:Reverse-engineeringgenenetworksfromexpressionprofilesisadifficultproblemforwhichamultitudeof techniqueshavebeendevelopedoverthelastdecade.TheyearlyorganizedDREAMchallengesallowforafairevaluation andunbiasedcomparisonofthesemethods. Results: We propose an inference algorithm that combines confidence matrices, computed as the standard scores from single-geneknockoutdata,withthedown-rankingoffeed-forwardedges.Substantialimprovementsonthepredictionscan beobtainedaftertheexecutionofthissecondstep. Conclusions: Our algorithm was awarded the best overall performance at the DREAM4 In Silico 100-gene network sub- challenge,provingtobeeffectiveininferringmedium-sizegeneregulatorynetworks.Thissuccessdemonstratesonceagain the decisive importance of gene expression data obtained after systematic gene perturbations and highlights the usefulnessofgraphanalysistoincreasethereliabilityofinference. Citation:PinnaA,SoranzoN,delaFuenteA(2010)FromKnockoutstoNetworks:EstablishingDirectCause-EffectRelationshipsthroughGraphAnalysis.PLoS ONE5(10):e12912.doi:10.1371/journal.pone.0012912 Editor:MarkIsalan,CenterforGenomicRegulation,Spain ReceivedApril2,2010;AcceptedJuly29,2010;PublishedOctober11,2010 Copyright: ? 2010 Pinna et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwaspartlysupportedbyTheRegionalAuthoritiesofSardinia(http://www.sardegnaricerche.it/).Thefundershadnoroleinstudydesign,data collectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:alf@crs4.it Introduction struc