Embedding mRNA Stability in Correlation Analysis of Time-Series Gene Expression Data 英文参考文献.docVIP

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Embedding mRNA Stability in Correlation Analysis of Time-Series Gene Expression Data 英文参考文献.doc

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Embedding mRNA Stability in Correlation Analysis of Time-Series Gene Expression Data 英文参考文献

EmbeddingmRNAStabilityinCorrelationAnalysisof Time-SeriesGeneExpressionData LorenzoFarina1*,AlbertoDeSantis1,SamantaSalvucci2,3,GiorgioMorelli3,IdaRuberti2 1DipartimentodiInformaticaeSistemistica‘‘AntonioRuberti’’,SapienzaUniversita`diRoma,Rome,Italy,2IstitutodiBiologiaePatologiaMolecolari,ConsiglioNazionale delleRicerche,Rome,Italy,3IstitutoNazionalediRicercapergliAlimentielaNutrizione,Rome,Italy Abstract Current methods for the identification of putatively co-regulated genes directly from gene expression time profiles are basedonthesimilarityofthetimeprofile.Suchassociationmetrics,despitetheircentralroleingenenetworkinferenceand machinelearning,havelargelyignoredtheimpactofdynamicsorvariationinmRNAstability.Hereweintroduceasimple, but powerful, new similarity metric called lead-lag R2 that successfully accounts for the properties of gene dynamics, includingvaryingmRNAdegradationanddelays.Usingyeastcell-cycletime-seriesgeneexpressiondata,wedemonstrate that the predictive power of lead-lag R2 for the identification of co-regulated genes is significantly higher than that of standardsimilaritymeasures,thusallowingtheselectionofalargenumberofentirelynewputativelyco-regulatedgenes. Furthermore,thelead-lagmetriccanalsobeusedtouncovertherelationshipbetweengeneexpressiontime-seriesandthe dynamicsofformationofmultipleproteincomplexes.Remarkably,wefoundahighlead-lagR2valueamonggenescoding foratransientcomplex. Citation:FarinaL,DeSantisA,SalvucciS,MorelliG,RubertiI(2008)EmbeddingmRNAStabilityinCorrelationAnalysisofTime-SeriesGeneExpressionData.PLoS ComputBiol4(8):e1000141.doi:10.1371/journal.pcbi.1000141 Editor:ManuelAresJr,UniversityofCaliforniaSantaCruz,UnitedStatesofAmerica ReceivedMarch14,2008;AcceptedJune24,2008;PublishedAugust1,2008 Copyright: ? 2008 Farina et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourc