Optimal flux spaces of genome-scale stoichiometric models are determined by a few subnetworks

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The metabolism of organisms can be studied with comprehensive stoichiometric models of their metabolic networks. Flux balance analysis (FBA) calculates optimal metabolic performance of stoichiometric models. However, detailed biological interpretation of FBA is limited because, in general, a huge number of flux patterns give rise to the same optimal performance. The complete description of the resulting optimal solution spaces was thus far a computationally intractable problem. Here we present CoPE-FBA: Comprehensive Polyhedra Enumeration Flux Balance Analysis, a computational method that solves this problem. CoPE-FBA indicates that the thousands to millions of optimal flux patterns result from a combinatorial explosion of flux patterns in just a few metabolic sub-networks. The entire optimal solution space can now be compactly described in terms of the topology of these sub-networks. CoPE-FBA simplifies the biological interpretation of stoichiometric models of metabolism, and provides a profound understanding of metabolic flexibility in optimal states.
Original languageEnglish
Article number580
JournalScientific Reports
Volume2
Issue number580
DOIs
Publication statusPublished - 2012

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@article{b915d3b3fbb44f4495354efcfe675e78,
title = "Optimal flux spaces of genome-scale stoichiometric models are determined by a few subnetworks",
abstract = "The metabolism of organisms can be studied with comprehensive stoichiometric models of their metabolic networks. Flux balance analysis (FBA) calculates optimal metabolic performance of stoichiometric models. However, detailed biological interpretation of FBA is limited because, in general, a huge number of flux patterns give rise to the same optimal performance. The complete description of the resulting optimal solution spaces was thus far a computationally intractable problem. Here we present CoPE-FBA: Comprehensive Polyhedra Enumeration Flux Balance Analysis, a computational method that solves this problem. CoPE-FBA indicates that the thousands to millions of optimal flux patterns result from a combinatorial explosion of flux patterns in just a few metabolic sub-networks. The entire optimal solution space can now be compactly described in terms of the topology of these sub-networks. CoPE-FBA simplifies the biological interpretation of stoichiometric models of metabolism, and provides a profound understanding of metabolic flexibility in optimal states.",
author = "S.M. Kelk and B.G. Olivier and L. Stougie and F.J. Bruggeman",
year = "2012",
doi = "10.1038/srep00580",
language = "English",
volume = "2",
journal = "Scientific Reports",
issn = "2045-2322",
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number = "580",

}

Optimal flux spaces of genome-scale stoichiometric models are determined by a few subnetworks. / Kelk, S.M.; Olivier, B.G.; Stougie, L.; Bruggeman, F.J.

In: Scientific Reports, Vol. 2, No. 580, 580, 2012.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Optimal flux spaces of genome-scale stoichiometric models are determined by a few subnetworks

AU - Kelk, S.M.

AU - Olivier, B.G.

AU - Stougie, L.

AU - Bruggeman, F.J.

PY - 2012

Y1 - 2012

N2 - The metabolism of organisms can be studied with comprehensive stoichiometric models of their metabolic networks. Flux balance analysis (FBA) calculates optimal metabolic performance of stoichiometric models. However, detailed biological interpretation of FBA is limited because, in general, a huge number of flux patterns give rise to the same optimal performance. The complete description of the resulting optimal solution spaces was thus far a computationally intractable problem. Here we present CoPE-FBA: Comprehensive Polyhedra Enumeration Flux Balance Analysis, a computational method that solves this problem. CoPE-FBA indicates that the thousands to millions of optimal flux patterns result from a combinatorial explosion of flux patterns in just a few metabolic sub-networks. The entire optimal solution space can now be compactly described in terms of the topology of these sub-networks. CoPE-FBA simplifies the biological interpretation of stoichiometric models of metabolism, and provides a profound understanding of metabolic flexibility in optimal states.

AB - The metabolism of organisms can be studied with comprehensive stoichiometric models of their metabolic networks. Flux balance analysis (FBA) calculates optimal metabolic performance of stoichiometric models. However, detailed biological interpretation of FBA is limited because, in general, a huge number of flux patterns give rise to the same optimal performance. The complete description of the resulting optimal solution spaces was thus far a computationally intractable problem. Here we present CoPE-FBA: Comprehensive Polyhedra Enumeration Flux Balance Analysis, a computational method that solves this problem. CoPE-FBA indicates that the thousands to millions of optimal flux patterns result from a combinatorial explosion of flux patterns in just a few metabolic sub-networks. The entire optimal solution space can now be compactly described in terms of the topology of these sub-networks. CoPE-FBA simplifies the biological interpretation of stoichiometric models of metabolism, and provides a profound understanding of metabolic flexibility in optimal states.

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JO - Scientific Reports

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