Probabilistic thermodynamic analysis of metabolic networks

Random sampling of metabolic fluxes can provide a comprehensive description of the capabilities of a metabolic network. However, current sampling approaches do not model thermodynamics explicitly, leading to inaccurate predictions of an organism's potential or actual metabolic operations. We pr...

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Bibliographic Details
Published in:Bioinformatics (Oxford, England) England), 2021-09, Vol.37 (18), p.2938-2945
Main Authors: Gollub, Mattia G, Kaltenbach, Hans-Michael, Stelling, Jörg
Format: Article
Language:English
Subjects:
Escherichia coli - metabolism
Metabolic Networks and Pathways
Models, Biological
Original Papers
Thermodynamics
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Summary:Random sampling of metabolic fluxes can provide a comprehensive description of the capabilities of a metabolic network. However, current sampling approaches do not model thermodynamics explicitly, leading to inaccurate predictions of an organism's potential or actual metabolic operations. We present a probabilistic framework combining thermodynamic quantities with steady-state flux constraints to analyze the properties of a metabolic network. It includes methods for probabilistic metabolic optimization and for joint sampling of thermodynamic and flux spaces. Applied to a model of Escherichia coli, we use the methods to reveal known and novel mechanisms of substrate channeling, and to accurately predict reaction directions and metabolite concentrations. Interestingly, predicted flux distributions are multimodal, leading to discrete hypotheses on E.coli's metabolic capabilities. Python and MATLAB packages available at https://gitlab.com/csb.ethz/pta. Supplementary data are available at Bioinformatics online.
ISSN:1367-4803
1367-4811
DOI:10.1093/bioinformatics/btab194