Decomposing flux distributions into elementary flux modes in genome-scale metabolic networks

Siu Hung Joshua Chan, Ping Ji

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Abstract

Motivation: Elementary flux mode (EFM) is a fundamental concept as well as a useful tool in metabolic pathway analysis. One important role of EFMs is that every flux distribution can be decomposed into a set of EFMs and a number of methods to study flux distributions originated from it. Yet finding such decompositions requires the complete set of EFMs, which is intractable in genomescale metabolic networks due to combinatorial explosion. Results: In this article, we proposed an algorithm to decompose flux distributions into EFMs in genome-scale networks. It is an iterative scheme of a mixed integer linear program. Unlike previous optimization models to find pathways, any feasible solutions can become EFMs in our algorithm. This advantage enables the algorithm to approximate the EFM of largest contribution to an objective reaction in a flux distribution. Our algorithm is able to find EFMs of flux distributions with complex structures, closer to the realistic case in which a cell is subject to various constraints. A case of Escherichia coli growth in the Lysogeny broth (LB) medium containing various carbon sources was studied. Essential metabolites and their syntheses were located. Information on the contribution of each carbon source not obvious from the apparent flux distribution was also revealed. Our work further confirms the utility of finding EFMs by optimization models in genome-scale metabolic networks. © The Author 2011. Published by Oxford University Press. All rights reserved.
Original languageEnglish
JournalBioinformatics
Volume27
Issue number16
Pages (from-to)2256-2262
Number of pages7
ISSN1367-4803
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine (all)
  • Escherichia coli
  • algorithm
  • article
  • bacterial genome
  • biological model
  • genetics
  • genomics
  • growth, development and aging
  • metabolism
  • Algorithms
  • Genome, Bacterial
  • Genomics
  • Metabolic Networks and Pathways
  • Models, Biological
  • ORIGINAL PAPERS
  • SYSTEMS BIOLOGY

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