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. 2018 Nov 20;12(Suppl 5):101.
doi: 10.1186/s12918-018-0619-1.

Improving the EFMs quality by augmenting their representativeness in LP methods

José F Hidalgo  1 , Jose A Egea  2 , Francisco Guil  3 , José M García  3
Affiliations

Improving the EFMs quality by augmenting their representativeness in LP methods

José F Hidalgo et al. BMC Syst Biol. .

Abstract

Background: Although cellular metabolism has been widely studied, its fully comprehension is still a challenge. A main tool for this study is the analysis of meaningful pieces of knowledge called modes and, in particular, specially interesting classes of modes such as pathways and Elementary Flux Modes (EFMs). Its study often has to deal with issues such as the appearance of infeasibilities or the difficulty of finding representative enough sets of modes that are free of repetitions. Mode extraction methods usually incorporate strategies devoted to mitigate this phenomena but they still get a high ratio of repetitions in the set of solutions.

Results: This paper presents a proposal to improve the representativeness of the full set of metabolic reactions in the set of computed modes by penalizing the eventual high frequency of occurrence of some reactions during the extraction. This strategy can be applied to any linear programming based extraction existent method.

Conclusions: Our strategy enhances the quality of a set of extracted EFMs favouring the presence of every reaction in it and improving the efficiency by mitigating the occurrence of repeated solutions. The new proposed strategy can complement other EFMs extraction methods based on linear programming. The obtained solutions are more likely to be diverse using less computing effort and improving the efficiency of the extraction.

Keywords: Flux modes; Linear programming; Metabolic networks; Pathways and EFMs; Representativeness and quality; Systems biology.

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Conflict of interest statement

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Not applicable.

Competing interests

All authors declare that they have no conflict of interest.

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Figures

Fig. 1
Fig. 1
Bargraph frequency/reaction. Bar graph for the frequencies of an experiment. Each bar corresponds to the frequency (y-axis) of one reaction. The order for the reactions in the x-axis is irrelevant but it is the same through all the experiments
Fig. 2
Fig. 2
Comparison of two experiments with different penalization. Bar graph grouping the frequencies of two experiments with different penalization (p =0 and p =2) over core E. coli metabolic model. A seed has 4 reactions. The experiments have consisted in 5000 iterations
Fig. 3
Fig. 3
Increment of frequency over an experiment without penalization. Bar graph representing the subtraction of the frequencies of two experiments with different penalization (p =0 and p =2) over core E. coli metabolic model. A seed has 4 reactions. The experiments have consisted in 5000 iterations
See this image and copyright information in PMC

References

    1. Thiele I, Palsson BØ. A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc. 2010;5(1):93–121. doi: 10.1038/nprot.2009.203. - DOI - PMC - PubMed
    1. Schmidt BJ, Ebrahim A, Metz TO, Adkins JN, Palsson BØ, Hyduke DR. Gim3e: condition-specific models of cellular metabolism developed from metabolomics and expression data. Bioinformatics. 2013;29(22):2900–8. doi: 10.1093/bioinformatics/btt493. - DOI - PMC - PubMed
    1. Schuster S, Hilgetag C. On elementary flux modes in biochemical reaction systems at steady state. J Biol Syst. 1994;2(02):165–82. doi: 10.1142/S0218339094000131. - DOI
    1. IBM. IBM ILOG CPLEX Optimizer. 2010. https://www.ibm.com/analytics/cplex-optimizer. Accessed 30 Mar 2018.
    1. Forrest J. Clp-coin-or linear program solver. In: DIMACS Workshop on COIN-OR, July: 2006. p. 17–20.

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