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Protein Networks as Logic Functions in Development and Cancer 英文参考文献.doc

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Protein Networks as Logic Functions in Development and Cancer 英文参考文献

ProteinNetworksasLogicFunctionsinDevelopment andCancer JanuszDutkowski1*,TreyIdeker1,2* 1Departments of Medicine and Bioengineering, University of California San Diego, La Jolla, California, United States of America, 2Institute for Genomic Medicine, UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Manybiologicalandclinicaloutcomesarebasednotonsingleproteins,butonmodulesofproteinsembeddedinprotein networks.Afundamentalquestionishowtheproteinswithineachmodulecontributetotheoverallmoduleactivity.Here, westudythemodulesunderlyingthreerepresentativebiologicalprograms relatedtotissuedevelopment,breastcancer metastasis, or progression of brain cancer, respectively. For each case we apply a new method, called Network-Guided Forests,toidentifypredictivemodulestogetherwithlogicfunctionswhichtietheactivityofeachmoduletotheactivityof itscomponentgenes.Theresultingmodulesimplementadiverserepertoireofdecisionlogicwhichcannotbecaptured using the simple approximations suggested in previous work such as gene summation or subtraction. We show that in cancer,certaincombinationsofoncogenesandtumorsuppressorsexertcompetingforcesonthesystem,suggestingthat medicalgeneticsshouldmovebeyondcataloguingindividualcancergenestocataloguingtheircombinatoriallogic. Citation: Dutkowski J, Ideker T (2011) Protein Networks as Logic Functions in Development and Cancer. PLoS Comput Biol 7(9): e1002180. doi:10.1371/ journal.pcbi.1002180 Editor:RussB.Altman,StanfordUniversity,UnitedStatesofAmerica ReceivedFebruary1,2011;AcceptedJuly17,2011;PublishedSeptember29,2011 Copyright:?2011Dutkowski,Ideker.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbygrantsRR031228andGM085764fromtheNationalInstitutesofHealth.Thefundershadnoroleinstudydesign,data collectionandanalysis,decisiontopublish,orprep