title: Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks.
abstract: Increasing amounts of sequence data are becoming available for a wide range of non-model organisms. Investigating and modelling the metabolic behaviour of those organisms is highly relevant to understand their biology and ecology. As sequences are often incomplete and poorly annotated, draft networks of their metabolism largely suffer from incompleteness. Appropriate gap-filling methods to identify and add missing reactions are therefore required to address this issue. However, current tools rely on phenotypic or taxonomic information, or are very sensitive to the stoichiometric balance of metabolic reactions, especially concerning the co-factors. This type of information is often not available or at least prone to errors for newly-explored organisms. Here we introduce Meneco, a tool dedicated to the topological gap-filling of genome-scale draft metabolic networks. Meneco reformulates gap-filling as a qualitative combinatorial optimization problem, omitting constraints raised by the stoichiometry of a metabolic network considered in other methods, and solves this problem using Answer Set Programming. Run on several artificial test sets gathering 10,800 degraded Escherichia coli networks Meneco was able to efficiently identify essential reactions missing in networks at high degradation rates, outperforming the stoichiometry-based tools in scalability. To demonstrate the utility of Meneco we applied it to two case studies. Its application to recent metabolic networks reconstructed for the brown algal model Ectocarpus siliculosus and an associated bacterium Candidatus Phaeomarinobacter ectocarpi revealed several candidate metabolic pathways for algal-bacterial interactions. Then Meneco was used to reconstruct, from transcriptomic and metabolomic data, the first metabolic network for the microalga Euglena mutabilis. These two case studies show that Meneco is a versatile tool to complete draft genome-scale metabolic networks produced from heterogeneous data, and to suggest relevant reactions that explain the metabolic capacity of a biological system.
authors.affiliation: Institute for Research in IT and Random Systems - IRISA, Université de Rennes 1, Rennes, France.|Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.|Irisa, CNRS, Rennes, France.|Dyliss, Inria, Rennes, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Prigent
authors.affiliation: Institute for Research in IT and Random Systems - IRISA, Université de Rennes 1, Rennes, France.|Irisa, CNRS, Rennes, France.|Dyliss, Inria, Rennes, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Frioux
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Dittami
authors.affiliation: Dyliss, Inria, Rennes, France.
authors.forename: Sven
authors.identifier: 0000-0002-5812-6963
authors.initials: S
authors.lastname: Thiele
authors.affiliation: Computer Science Laboratory of Nantes Atlantique - LINA UMR6241, Université de Nantes, Nantes, France.
authors.forename: Abdelhalim
authors.initials: A
authors.lastname: Larhlimi
authors.affiliation: Institute for Research in IT and Random Systems - IRISA, Université de Rennes 1, Rennes, France.|Irisa, CNRS, Rennes, France.|Dyliss, Inria, Rennes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Collet
authors.affiliation: Molecular Genetics, Genomics and Microbiology - GMGM, Université de Strasbourg, Strasbourg, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gutknecht
authors.affiliation: Institute for Research in IT and Random Systems - IRISA, Université de Rennes 1, Rennes, France.|Irisa, CNRS, Rennes, France.|Dyliss, Inria, Rennes, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Got
authors.affiliation: Computer Science Laboratory of Nantes Atlantique - LINA UMR6241, Université de Nantes, Nantes, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Eveillard
authors.affiliation: Computer Science Laboratory of Nantes Atlantique - LINA UMR6241, Université de Nantes, Nantes, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Bourdon
authors.affiliation: Molecular Genetics, Genomics and Microbiology - GMGM, Université de Strasbourg, Strasbourg, France.|GMGM, CNRS, Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Plewniak
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Tonon
authors.affiliation: Institute for Research in IT and Random Systems - IRISA, Université de Rennes 1, Rennes, France.|Irisa, CNRS, Rennes, France.|Dyliss, Inria, Rennes, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Siegel
mesh_terms: D000465:Algorithms; D030541:Databases, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016678:Genome / Q000235:genetics; D023281:Genomics / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055442:Metabolome / Q000235:genetics*; D012984:Software; D059467:Transcriptome / Q000235:genetics*