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Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks

Thermodynamics constrains the flow of matter in a reaction network to occur through routes along which the Gibbs energy decreases, implying that viable steady-state flux patterns should be void of closed reaction cycles. Identifying and removing cycles in large reaction networks can unfortunately be...

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Autores principales: De Martino, Daniele, Capuani, Fabrizio, Mori, Matteo, De Martino, Andrea, Marinari, Enzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937828/
https://www.ncbi.nlm.nih.gov/pubmed/24958259
http://dx.doi.org/10.3390/metabo3040946
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author De Martino, Daniele
Capuani, Fabrizio
Mori, Matteo
De Martino, Andrea
Marinari, Enzo
author_facet De Martino, Daniele
Capuani, Fabrizio
Mori, Matteo
De Martino, Andrea
Marinari, Enzo
author_sort De Martino, Daniele
collection PubMed
description Thermodynamics constrains the flow of matter in a reaction network to occur through routes along which the Gibbs energy decreases, implying that viable steady-state flux patterns should be void of closed reaction cycles. Identifying and removing cycles in large reaction networks can unfortunately be a highly challenging task from a computational viewpoint. We propose here a method that accomplishes it by combining a relaxation algorithm and a Monte Carlo procedure to detect loops, with ad hoc rules (discussed in detail) to eliminate them. As test cases, we tackle (a) the problem of identifying infeasible cycles in the E. coli metabolic network and (b) the problem of correcting thermodynamic infeasibilities in the Flux-Balance-Analysis solutions for 15 human cell-type-specific metabolic networks. Results for (a) are compared with previous analyses of the same issue, while results for (b) are weighed against alternative methods to retrieve thermodynamically viable flux patterns based on minimizing specific global quantities. Our method, on the one hand, outperforms previous techniques and, on the other, corrects loopy solutions to Flux Balance Analysis. As a byproduct, it also turns out to be able to reveal possible inconsistencies in model reconstructions.
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spelling pubmed-39378282014-05-27 Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks De Martino, Daniele Capuani, Fabrizio Mori, Matteo De Martino, Andrea Marinari, Enzo Metabolites Article Thermodynamics constrains the flow of matter in a reaction network to occur through routes along which the Gibbs energy decreases, implying that viable steady-state flux patterns should be void of closed reaction cycles. Identifying and removing cycles in large reaction networks can unfortunately be a highly challenging task from a computational viewpoint. We propose here a method that accomplishes it by combining a relaxation algorithm and a Monte Carlo procedure to detect loops, with ad hoc rules (discussed in detail) to eliminate them. As test cases, we tackle (a) the problem of identifying infeasible cycles in the E. coli metabolic network and (b) the problem of correcting thermodynamic infeasibilities in the Flux-Balance-Analysis solutions for 15 human cell-type-specific metabolic networks. Results for (a) are compared with previous analyses of the same issue, while results for (b) are weighed against alternative methods to retrieve thermodynamically viable flux patterns based on minimizing specific global quantities. Our method, on the one hand, outperforms previous techniques and, on the other, corrects loopy solutions to Flux Balance Analysis. As a byproduct, it also turns out to be able to reveal possible inconsistencies in model reconstructions. Molecular Diversity Preservation International (MDPI) 2013-10-14 /pmc/articles/PMC3937828/ /pubmed/24958259 http://dx.doi.org/10.3390/metabo3040946 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
De Martino, Daniele
Capuani, Fabrizio
Mori, Matteo
De Martino, Andrea
Marinari, Enzo
Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title_full Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title_fullStr Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title_full_unstemmed Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title_short Counting and Correcting Thermodynamically Infeasible Flux Cycles in Genome-Scale Metabolic Networks
title_sort counting and correcting thermodynamically infeasible flux cycles in genome-scale metabolic networks
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937828/
https://www.ncbi.nlm.nih.gov/pubmed/24958259
http://dx.doi.org/10.3390/metabo3040946
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