Systematic construction of kinetic models from genome-scale metabolic networks

Stanford, Natalie J. and Lubitz, Timo and Smallbone, Kieran and Klipp, Edda and Mendes, Pedro and Liebermeister, Wolfram (2013) Systematic construction of kinetic models from genome-scale metabolic networks. PLoS ONE, 8 (11). e79195.

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Abstract

The 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.

Item Type: Article
Subjects: MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User: Dr Kieran Smallbone
Date Deposited: 12 Jul 2015
Last Modified: 20 Oct 2017 14:13
URI: http://eprints.maths.manchester.ac.uk/id/eprint/2337

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