Cardinality optimization in constraint-based modelling: application to human metabolism
Bioinformatics, vol. 39
Abstract
MOTIVATION: Several applications in constraint-based modelling can be mathematically formulated as cardinality optimization problems involving the minimization or maximization of the number of nonzeros in a vector. These problems include testing for stoichiometric consistency, testing for flux consistency, testing for thermodynamic flux consistency, computing sparse solutions to flux balance analysis problems and computing the minimum number of constraints to relax to render an infeasible flux balance analysis problem feasible. Such cardinality optimization problems are computationally complex, with no known polynomial time algorithms capable of returning an exact and globally optimal solution. RESULTS: By approximating the zero-norm with nonconvex continuous functions, we reformulate a set of cardinality optimization problems in constraint-based modelling into a difference of convex functions. We implemented and numerically tested novel algorithms that approximately solve the reformulated problems using a sequence of convex programs. We applied these algorithms to various biochemical networks and demonstrate that our algorithms match or outperform existing related approaches. In particular, we illustrate the efficiency and practical utility of our algorithms for cardinality optimization problems that arise when extracting a model ready for thermodynamic flux balance analysis given a human metabolic reconstruction. AVAILABILITY AND IMPLEMENTATION: Open source scripts to reproduce the results are here https://github.com/opencobra/COBRA.papers/2023_cardOpt with general purpose functions integrated within the COnstraint-Based Reconstruction and Analysis toolbox: https://github.com/opencobra/cobratoolbox.
Authors 5
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Ronan M. T. Fleming corresponding Aachen Metabolomics and Analytics Centre Leiden Academic Centre for Drug Research
Leiden University · National University of Ireland · University of Luxembourg · Ollscoil na Gaillimhe – University of Galway · Luxembourg Centre for Systems Biomedicine
Affiliation as printed
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing , Belvaux L-4362, Luxembourg
Metabolomics and Analytics Center, Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76 , Leiden 2333 CC, The Netherlands
School of Medicine, National University of Ireland, University Rd , Galway H91 TK33, Ireland
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University of Luxembourg · Luxembourg Centre for Systems Biomedicine
Affiliation as printed
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing , Belvaux L-4362, Luxembourg
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University of Luxembourg · University of Southampton · Luxembourg Centre for Systems Biomedicine
Affiliation as printed
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing , Belvaux L-4362, Luxembourg
Mathematical Sciences School, University of Southampton, University Road , Southampton SO17 1BJ, United Kingdom
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Affiliation as printed
Metabolomics and Analytics Center, Leiden Academic Centre for Drug Research, Leiden University, Wassenaarseweg 76 , Leiden 2333 CC, The Netherlands
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National University of Ireland · Ollscoil na Gaillimhe – University of Galway
Affiliation as printed
School of Medicine, National University of Ireland, University Rd , Galway H91 TK33, Ireland
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