Sampling the Solution Space in Genome-Scale Metabolic Networks Reveals Transcriptional Regulation in Key Enzymes 英文参考文献.docVIP

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Sampling the Solution Space in Genome-Scale Metabolic Networks Reveals Transcriptional Regulation in Key Enzymes 英文参考文献.doc

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Sampling the Solution Space in Genome-Scale Metabolic Networks Reveals Transcriptional Regulation in Key Enzymes 英文参考文献

SamplingtheSolutionSpaceinGenome-ScaleMetabolic NetworksRevealsTranscriptionalRegulationinKey Enzymes SergioBordel,RasmusAgren,JensNielsen* SystemsBiology,DepartmentofChemicalandBiologicalEngineering,ChalmersUniversityofTechnology,Gothenburg,Sweden Abstract Genome-scalemetabolicmodelsareavailableforanincreasingnumberoforganismsandcanbeusedtodefinetheregion offeasiblemetabolicfluxdistributions.Inthisworkweuseasconstraintsasmallsetofexperimentalmetabolicfluxes,which reduces the region of feasible metabolic states. Once the region of feasible fluxdistributions has beendefined, a set of possible flux distributions is obtained by random sampling and the averages and standard deviations for each of the metabolicfluxesinthegenome-scalemodelarecalculated.Thesevaluesallowestimationofthesignificanceofchangefor eachreactionratebetweendifferentconditionsandcomparisonofitwiththesignificanceofchangeingenetranscription for the corresponding enzymes. The comparison of flux change and gene expression allows identification of enzymes showing a significant correlation between flux change and expression change (transcriptional regulation) as well as reactionswhosefluxchangeislikelytobedrivenonlybychangesinthemetaboliteconcentrations(metabolicregulation). Thechangesduetogrowthonfourdifferentcarbonsourcesandasaconsequenceoffivegenedeletionswereanalyzedfor Saccharomycescerevisiae.Theenzymeswithtranscriptionalregulationshowedenrichmentincertaintranscriptionfactors. Thishasnotbeenpreviouslyreported.Theinformationprovidedbythepresentedmethodcouldguidethediscoveryof newmetabolicengineeringstrategiesortheidentificationofdrugtargetsfortreatmentofmetabolicdiseases. Citation: Bordel S, Agren R, Nielsen J (2010) Sampling the Solution Space in Genome-Scale Metabolic Networks Reveals Transcriptional Regulation in Key Enzymes.PLoSComputBiol6(7):e1000859.doi:10.1371/journal.pcbi.1000859 Editor:JenniferL.Reed,UniversityofWisconsin-Madison,UnitedStatesofAmerica ReceivedMarch18,2010;AcceptedJune14,2010