Construction of feasible and accurate kinetic models of metabolism: a Bayesian approach

Saa, Pedro A. and Nielsen, Lars K. (2016) Construction of feasible and accurate kinetic models of metabolism: a Bayesian approach. Scientific Reports, 6 . doi:10.1038/srep29635

Author Saa, Pedro A.
Nielsen, Lars K.
Title Construction of feasible and accurate kinetic models of metabolism: a Bayesian approach
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-07-15
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep29635
Open Access Status DOI
Volume 6
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
Kinetic models are essential to quantitatively understand and predict the behaviour of metabolic networks. Detailed and thermodynamically feasible kinetic models of metabolism are inherently difficult to formulate and fit. They have a large number of heterogeneous parameters, are non-linear and have complex interactions. Many powerful fitting strategies are ruled out by the intractability of the likelihood function. Here, we have developed a computational framework capable of fitting feasible and accurate kinetic models using Approximate Bayesian Computation. This framework readily supports advanced modelling features such as model selection and model-based experimental design. We illustrate this approach on the tightly-regulated mammalian methionine cycle. Sampling from the posterior distribution, the proposed framework generated thermodynamically feasible parameter samples that converged on the true values, and displayed remarkable prediction accuracy in several validation tests. Furthermore, a posteriori analysis of the parameter distributions enabled appraisal of the systems properties of the network (e.g., control structure) and key metabolic regulations. Finally, the framework was used to predict missing allosteric interactions.
Keyword Mathematical models
Kinetic models
Metabolic networks
Approximate Bayesian Computation (ABC)
Mammalian methionine cycle
Allosteric interactions
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
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