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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2013
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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. |
format | Online Article Text |
id | pubmed-3937828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
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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