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Construction of a Genome-Scale Kinetic Model of Mycobacterium Tuberculosis Using Generic Rate Equations

Manchester Institute of Biotechnology, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
Author to whom correspondence should be addressed.
Metabolites 2012, 2(3), 382-397;
Received: 29 March 2012 / Revised: 7 June 2012 / Accepted: 25 June 2012 / Published: 3 July 2012
(This article belongs to the Special Issue Metabolism and Systems Biology)
The study of biological systems at the genome scale helps us understand fundamental biological processes that govern the activity of living organisms and regulate their interactions with the environment. Genome-scale metabolic models are usually analysed using constraint-based methods, since detailed rate equations and kinetic parameters are often missing. However, constraint-based analysis is limited in capturing the dynamics of cellular processes. In this paper, we present an approach to build a genome-scale kinetic model of Mycobacterium tuberculosis metabolism using generic rate equations. M. tuberculosis causes tuberculosis which remains one of the largest killer infectious diseases. Using a genetic algorithm, we estimated kinetic parameters for a genome-scale metabolic model of M. tuberculosis based on flux distributions derived from Flux Balance Analysis. Our results show that an excellent agreement with flux values is obtained under several growth conditions, although kinetic parameters may vary in different conditions. Parameter variability analysis indicates that a high degree of redundancy remains present in model parameters, which suggests that the integration of other types of high-throughput datasets will enable the development of better constrained models accounting for a variety of in vivo phenotypes. View Full-Text
Keywords: tuberculosis; metabolism, kinetic model; systems biology tuberculosis; metabolism, kinetic model; systems biology
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Adiamah, D.A.; Schwartz, J.-M. Construction of a Genome-Scale Kinetic Model of Mycobacterium Tuberculosis Using Generic Rate Equations. Metabolites 2012, 2, 382-397.

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