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Finding Minimum Reaction Cuts of Metabolic Networks Under a Boolean Model Using Integer Programming and Feedback Vertex Sets

Finding Minimum Reaction Cuts of Metabolic Networks Under a Boolean Model Using Integer Programming and Feedback Vertex Sets
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Author(s): Takeyuki Tamura (Kyoto University, Japan), Kazuhiro Takemoto (Graduate School of Frontier Sciences, Japan) and Tatsuya Akutsu (Kyoto University, Japan)
Copyright: 2012
Pages: 18
Source title: Computer Engineering: Concepts, Methodologies, Tools and Applications
Source Author(s)/Editor(s): Information Resources Management Association (USA)
DOI: 10.4018/978-1-61350-456-7.ch318

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Abstract

In this paper, the authors consider the problem of, given a metabolic network, a set of source compounds and a set of target compounds, finding a minimum size reaction cut, where a Boolean model is used as a model of metabolic networks. The problem has potential applications to measurement of structural robustness of metabolic networks and detection of drug targets. They develop an integer programming-based method for this optimization problem. In order to cope with cycles and reversible reactions, they further develop a novel integer programming (IP) formalization method using a feedback vertex set (FVS). When applied to an E. coli metabolic network consisting of Glycolysis/Glyconeogenesis, Citrate cycle and Pentose phosphate pathway obtained from KEGG database, the FVS-based method can find an optimal set of reactions to be inactivated much faster than a naive IP-based method and several times faster than a flux balance-based method. The authors also confirm that our proposed method works even for large networks and discuss the biological meaning of our results.

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