Directing Experimental Biology A Case Study in Mitochondrial Biogenesis 英文参考文献.docVIP

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Directing Experimental Biology A Case Study in Mitochondrial Biogenesis 英文参考文献.doc

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Directing Experimental Biology A Case Study in Mitochondrial Biogenesis 英文参考文献

DirectingExperimentalBiology:ACaseStudyin MitochondrialBiogenesis MatthewA.Hibbs1,2.,ChadL.Myers1,2,3.,CurtisHuttenhower1,2.,DavidC.Hess1,KaiLi2,AmyA. Caudy1,OlgaG.Troyanskaya1,2* 1Lewis-SiglerInstituteforIntegrativeGenomics,PrincetonUniversity,CarlIcahnLaboratory,Princeton,NewJersey,UnitedStatesofAmerica,2DepartmentofComputer Science,PrincetonUniversity,Princeton,NewJersey,UnitedStatesofAmerica,3DepartmentofComputerScienceandEngineering,UniversityofMinnesota,Minneapolis, Minnesota,UnitedStatesofAmerica Abstract Computationalapproacheshavepromisedtoorganizecollectionsoffunctionalgenomicsdataintotestablepredictionsof gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentallyvalidatedonalargescale,leavingmanybioinformaticmethodsunprovenandunderutilizedinthebiology community.Further,itremainsunclearwhatbiologicalconcernsshouldbetakenintoaccountwhenusingcomputational methodstodrivereal-worldexperimentalefforts.Toinvestigatetheseconcernsandtoestablishtheutilityofcomputational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae . The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407).Hereweanalyzeandexploretheresultsofthisstudythatarebroadlyapplicablefor computationalistsapplyinggenefunctionpredictiontechniques,includinganewexperimentalcomparisonwith48genes representingthegenomicbackground.Ourstudyleadstoseveralconclusionsthatareimportanttoconsiderwhendriving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participateinatleastonebiologicalprocess,weconfirmthatgeneswithknownfunctionscanstillbestrongcandidatesfor annotationofadditionalgenefunctions.Wefindthatdifferentanalys