Systematic Construction of Kinetic Models from Genome-Scale Metabolic Networks

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dc.contributor.authorStanford, Natalie J.en
dc.contributor.authorLubitz, Timoen
dc.contributor.authorSmallbone, Kieranen
dc.contributor.authorKlipp, Eddaen
dc.contributor.authorMendes, Pedroen
dc.contributor.authorLiebermeister, Wolframen
dc.date.accessioned2018-10-16T16:41:24Zen
dc.date.available2018-10-16T16:41:24Zen
dc.date.issued2013-09-14en
dc.description.abstractThe quantitative effects of environmental and genetic perturbations on metabolism can be studied in silico using kinetic models. We present a strategy for large-scale model construction based on a logical layering of data such as reaction fluxes, metabolite concentrations, and kinetic constants. The resulting models contain realistic standard rate laws and plausible parameters, adhere to the laws of thermodynamics, and reproduce a predefined steady state. These features have not been simultaneously achieved by previous workflows. We demonstrate the advantages and limitations of the workflow by translating the yeast consensus metabolic network into a kinetic model. Despite crudely selected data, the model shows realistic control behaviour, a stable dynamic, and realistic response to perturbations in extracellular glucose concentrations. The paper concludes by outlining how new data can continuously be fed into the workflow and how iterative model building can assist in directing experiments.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0079195en
dc.identifier.eissn1932-6203en
dc.identifier.issue11en
dc.identifier.othere79195en
dc.identifier.pmid24324546en
dc.identifier.urihttp://hdl.handle.net/10919/85383en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSystematic Construction of Kinetic Models from Genome-Scale Metabolic Networksen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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