A Novel Method Incorporating Gene Ontology Information for Unsupervised Clustering and Feature Selection 英文参考文献.docVIP

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A Novel Method Incorporating Gene Ontology Information for Unsupervised Clustering and Feature Selection 英文参考文献.doc

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A Novel Method Incorporating Gene Ontology Information for Unsupervised Clustering and Feature Selection 英文参考文献

ANovelMethodIncorporatingGeneOntology InformationforUnsupervisedClusteringandFeature Selection ShireeshSrivastava1¤,LinxiaZhang1,RongJin2,ChristinaChan1,2,3* 1DepartmentofChemicalEngineeringandMaterialsScience,MichiganStateUniversity,EastLansing,Michigan,UnitedStatesofAmerica,2DepartmentofComputer ScienceandEngineering,MichiganStateUniversity, EastLansing,Michigan,UnitedStatesofAmerica, 3DepartmentofBiochemistryandMolecularBiology,Michigan StateUniversity,EastLansing,Michigan,UnitedStatesofAmerica Abstract Background:Amongtheprimarygoalsofmicroarrayanalysisistheidentificationofgenesthatcoulddistinguishbetween different phenotypes (feature selection). Previous studies indicate that incorporating prior information of the genes’ functioncouldhelpidentifyphysiologicallyrelevantfeatures.However,currentmethodsthatincorporatepriorfunctional informationdonotprovidearelativeestimateoftheeffectofdifferentgenesonthebiologicalprocessesofinterest. Results:Here,wepresentamethodthatintegratesgeneontology(GO)informationandexpressiondatausingBayesian regression mixture models to perform unsupervised clustering of the samples and identify physiologically relevant discriminating features. As a model application, the method was applied to identify the genes that play a role in the cytotoxic responses of human hepatoblastoma cell line (HepG2) to saturated fatty acid (SFA) and tumor necrosis factor (TNF)-a,ascomparedtothenon-toxicresponsetotheunsaturatedFFAs(UFA)andTNF-a.Incorporationofpriorknowledge ledtoabetterdiscriminationofthetoxicphenotypesfromtheothers.ThemodelidentifiedrolesoflysosomalATPasesand adenylatecyclase(AC9)inthetoxicityofpalmitate.TovalidatetheroleofACinpalmitate-treatedcells,wemeasuredthe intracellularlevelsofcyclicAMP(cAMP).ThecAMPlevelswerefoundtobesignificantlyreducedbypalmitatetreatmentand notbytheotherFFAs,inaccordancewiththemodelselectionofAC9. Conclusions: A framework is presented that incorporates prior ontology information, which helped to (a) perform