A mixed-integer linear programming approach to the reduction of genome-scale metabolic networks. 2017

Annika Röhl, and Alexander Bockmayr
Department of Mathematics and Computer Science, Freie Universität Berlin, Arnimallee 6, Berlin, Germany. annika.roehl@fu-berlin.de.

Constraint-based analysis has become a widely used method to study metabolic networks. While some of the associated algorithms can be applied to genome-scale network reconstructions with several thousands of reactions, others are limited to small or medium-sized models. In 2015, Erdrich et al. introduced a method called NetworkReducer, which reduces large metabolic networks to smaller subnetworks, while preserving a set of biological requirements that can be specified by the user. Already in 2001, Burgard et al. developed a mixed-integer linear programming (MILP) approach for computing minimal reaction sets under a given growth requirement. Here we present an MILP approach for computing minimum subnetworks with the given properties. The minimality (with respect to the number of active reactions) is not guaranteed by NetworkReducer, while the method by Burgard et al. does not allow specifying the different biological requirements. Our procedure is about 5-10 times faster than NetworkReducer and can enumerate all minimum subnetworks in case there exist several ones. This allows identifying common reactions that are present in all subnetworks, and reactions appearing in alternative pathways. Applying complex analysis methods to genome-scale metabolic networks is often not possible in practice. Thus it may become necessary to reduce the size of the network while keeping important functionalities. We propose a MILP solution to this problem. Compared to previous work, our approach is more efficient and allows computing not only one, but even all minimum subnetworks satisfying the required properties.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016480 Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). Campylobacter pylori,Campylobacter pylori subsp. pylori,Campylobacter pyloridis,Helicobacter nemestrinae
D016678 Genome The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA. Genomes
D016680 Genome, Bacterial The genetic complement of a BACTERIA as represented in its DNA. Bacterial Genome,Bacterial Genomes,Genomes, Bacterial
D053858 Metabolic Networks and Pathways Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites. Metabolic Networks,Metabolic Pathways,Metabolic Network,Metabolic Pathway,Network, Metabolic,Networks, Metabolic,Pathway, Metabolic,Pathways, Metabolic
D019295 Computational Biology A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets. Bioinformatics,Molecular Biology, Computational,Bio-Informatics,Biology, Computational,Computational Molecular Biology,Bio Informatics,Bio-Informatic,Bioinformatic,Biologies, Computational Molecular,Biology, Computational Molecular,Computational Molecular Biologies,Molecular Biologies, Computational

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