Simultaneous Genome-Wide Inference of Physical, Genetic, Regulatory, and Functional Pathway Components 英文参考文献.docVIP

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Simultaneous Genome-Wide Inference of Physical, Genetic, Regulatory, and Functional Pathway Components 英文参考文献.doc

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Simultaneous Genome-Wide Inference of Physical, Genetic, Regulatory, and Functional Pathway Components 英文参考文献

SimultaneousGenome-WideInferenceofPhysical, Genetic,Regulatory,andFunctionalPathway Components ChristopherY.Park1,2,DavidC.Hess3,CurtisHuttenhower4*,OlgaG.Troyanskaya1,2* 1Lewis-SiglerInstitute forIntegrativeGenomics,PrincetonUniversity, Princeton,NewJersey,UnitedStatesofAmerica, 2DepartmentofComputerScience,Princeton University, Princeton, New Jersey, United States of America, 3Department of Biology, Santa Clara University, Santa Clara, California, United States of America, 4DepartmentofBiostatistics,HarvardSchoolofPublicHealth,Boston,Massachusetts,UnitedStatesofAmerica Abstract Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactionsandmodificationstoindirectregulatoryrelationships.Onegoalofsystemsbiologyistobridgethreeaspectsof thiscomplexity:thegrowingbodyofhigh-throughputdataassayingtheseinteractions;thespecificinteractionsinwhich individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data.Thisresultsinacomprehensivecompendiumofwhole-genomenetworksforyeast,derivedfrom,3,500experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory) to specific (e.g. phosphorylation or transcriptional regulation). We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supportedbyrecentpublications.Additionally,14specificpredictedinteractionsinDNAtopologicalchangeandprotein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifyingthepresenceofsmall-worldpropertiesandenrichmentforrecurringnetworkmotifs.Thiscompendiumofphysical, synthetic, regulatory, and functional interaction netwo