Abstract Motivation Elementary flux modes (EFMs) are a key tool for analyzing genome-scale metabolic networks, and several methods have been proposed to compute them. Among them, those based on solving linear programming (LP) problems are known to be very efficient if the main interest lies in computing large enough sets of EFMs. Results Here, we propose a new method called EFM-Ta that boosts the efficiency rate by analyzing the information provided by the LP solver. We base our method on a further study of the final tableau of the simplex method. By performing additional elementary steps and avoiding trivial solutions consisting of two cycles, we obtain many more EFMs for each LP problem posed, improving the efficiency rate of previously proposed methods by more than one order of magnitude. Availability and implementation Software is freely available at https://github.com/biogacop/Boost_LP_EFM. Supplementary information Supplementary data are available at Bioinformatics online.

Structural analysis of constraint-based metabolic network models attempts to find the network’s properties by searching for subsets of suitable modes or Elementary Flux Modes (EFMs). One useful approach is based on Linear Program (LP) techniques, which introduce an objective function to convert the stoichiometric and thermodynamic constraints into a linear program (LP), using additional constraints to generate different nontrivial modes. This work introduces FLFS-FC (Fixed Length Function Sampling with Flux Coupling), a new approach to increase the efficiency of generation of large sets of different EFMs for the network. FLFS-FC is based on the importance of the length of the objective functions used in the associated LP problem and the imposition of additional negative constraints. Our proposal overrides some of the known drawbacks associated with the EFM extraction, such as the appearance of unfeasible problems or multiple repeated solutions arising from different LP problems.

BackgroundAlthough 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.ResultsThis 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.ConclusionsOur 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.

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Background: The study of structural properties of a metabolic network can be approached by analyzing its Elementary Flux Modes (EFMs). Even in cases in which this set can be fully computed, its large cardinality makes it difficult to interpret the information contained in it. Results: This paper presents a proposal to improve the study of structural properties of a network by using clustering techniques in its set of EFMs. It is shown how some properties of this set such as their length distribution or the reaction participation can be better elucidated after a clustering process and how it allows for a better comprehension of the possible behaviours of the network. Conclusions: Our clustering approach can help in the extraction of relevant biological significance from the set of EFMs and can be applied to different problems related to the structural properties of the network under study