Genome-Scale Reconstruction of Escherichia colis Transcriptional and Translational Machinery A Knowledge Base, Its Mathematical Formulation, and Its Functional Characterization 英文参考文献.docVIP

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Genome-Scale Reconstruction of Escherichia colis Transcriptional and Translational Machinery A Knowledge Base, Its Mathematical Formulation, and Its Functional Characterization 英文参考文献.doc

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Genome-Scale Reconstruction of Escherichia colis Transcriptional and Translational Machinery A Knowledge Base, Its Mathematical Formulation, and Its Functional Characterization 英文参考文献

Genome-ScaleReconstructionofEscherichiacoli’s TranscriptionalandTranslationalMachinery:A KnowledgeBase,ItsMathematicalFormulation,andIts FunctionalCharacterization InesThiele1,2,NeemaJamshidi2,RonanM.T.Fleming2,Bernhard?.Palsson2* 1Ph.D.PrograminBioinformatics,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica, 2SystemsBiologyResearchGroup,Bioengineering Department,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract Metabolic network reconstructions represent valuable scaffolds for ‘-omics’ data integration and are used to computationally interrogate network properties. However, they do not explicitly account for the synthesis of macromolecules(i.e.,proteinsandRNA).Here,wepresentthefirstgenome-scale,fine-grainedreconstructionofEscherichia coli’s transcriptional and translational machinery, which produces 423 functional gene products in a sequence-specific manner and accounts for all necessary chemical transformations. Legacy data from over 500 publications and three databaseswerereviewed,andmanypathwayswereconsidered,includingstableRNAmaturationandmodification,protein complexformation,andiron–sulfurclusterbiogenesis.Thisreconstructionrepresentsthemostcomprehensiveknowledge base for these important cellular functions in E. coli and is unique in its scope. Furthermore, it was converted into a mathematicalmodelandusedto:(1)quantitativelyintegrategeneexpressiondataasreactionconstraintsand(2)compute functional network states, which were compared to reported experimental data. For example, the model predicted accuratelytheribosomeproduction,withoutanyparameterization.Also,insilicorRNAoperondeletionsuggestedthata highRNApolymerasedensityontheremainingrRNAoperonsisneededtoreproducethereportedexperimentalribosome numbers.Moreover,functionalproteinmodulesweredetermined,andmanywerefoundtocontaingeneproductsfrom multiplesubsystems,highlightingthefunctionalinteractionoftheseproteins.Thisgenome-scalereconstruction