Function-Based Discovery of Significant Transcriptional Temporal Patterns in Insulin Stimulated Muscle Cells 英文参考文献.docVIP

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Function-Based Discovery of Significant Transcriptional Temporal Patterns in Insulin Stimulated Muscle Cells 英文参考文献.doc

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Function-Based Discovery of Significant Transcriptional Temporal Patterns in Insulin Stimulated Muscle Cells 英文参考文献

Function-BasedDiscoveryofSignificantTranscriptional TemporalPatternsinInsulinStimulatedMuscleCells BarbaraDiCamillo1,BrianA.Irving2,JillSchimke2,TizianaSanavia1,GiannaToffolo1,ClaudioCobelli1, K.SreekumaranNair2* 1Information Engineering Department, University of Padova, Padova, Italy, 2Division of Endocrinology, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic Rochester,Rochester,Minnesota,UnitedSatesofAmerica Abstract Background:Insulinactiononproteinsynthesis(translationoftranscripts)andpost-translationalmodifications,especiallyof thoseinvolvingthereversiblemodificationssuchasphosphorylationofvarioussignalingproteins,areextensivelystudied butinsulineffectontranscriptionofgenes,especiallyoftranscriptionaltemporalpatternsremainstobefullydefined. Methodology/PrincipalFindings:Toidentifysignificanttranscriptionaltemporalpatternsweutilizedprimarydifferentiated ratskeletalmusclemyotubeswhichweretreatedwithinsulinandsampleswerecollectedevery20minfor8hours.Pooled samplesateveryhourwereanalyzedbygenearrayapproachtomeasuretranscriptlevels.Thepatternsoftranscriptlevels wereanalyzedbasedonanovelmethodthatintegratesselection,clustering,andfunctionalannotationtofindthemain temporal patterns associated to functional groups of differentially expressed genes. 326 genes were found to be differentiallyexpressedinresponsetoinvitroinsulinadministrationinskeletalmusclemyotubes.Approximately20%ofthe genes that were differentially expressed were identified as belonging to the insulin signaling pathway. Characteristic transcriptionaltemporalpatternsinclude:(a)aslowandgradualdecreaseingeneexpression,(b)agradualincreaseingene expressionreachingapeakatabout5hoursandthenreachingaplateauoraninitialdecreaseandotherdifferentvariable patternofincreaseingeneexpressionovertime. Conclusion/Significance:Thenewmethodallowsidentifyingcharacteristicdynamicresponsestoinsulinstimulus,common toanumberofgenesandassociatedtothesamefunctionalgroup.Theresultsdemonstratethatinsulintreatmentelicited