Overview

I use logic programming to study the metabolism of non-model organisms: facilitate the refinement of metabolic networks, propose solution to select communities of interest within microbiotas.

I focus my research on graph-based or hybrid (graph-based and constraint-based) modeling of metabolism based on Answer Set Programming ↗ and the solving of combinatorial optimization problems. I contributed to the meneco ↗ project, a tool dedicated to gap-fill genome-scale metablic networks by selecting a minimal number of reactions from a database, in order to ensure the producibility of compounds of interest (PLOS Computational Biology 2017). I then collaborated to the creation of a hybrid method for metabolism gap-filling, enabling to optimize not only the constraint-based producibility of metabolites, but also the reaction of interest with the Flux Balance Analysis framework (LPNMR Conference 2017, best Student Paper). I now focus on the selection of communities within large microbiotas.

Thesis

Investigating host-microbiota cooperation with gap-filling optimisation problems

PhD defense on November 19th, 2018 at Inria-IRISA Rennes.

Jury composition

Abstract
Systems biology relies on computational biology to integrate knowledge and data, for a better understanding of organisms’ physiology. Challenges reside in the applicability of methods and tools to non-model organisms, for which data is limited, and more generally to host-microbiota systems. Understanding the interactions in the later is an objective of systems ecology. Metabolic networks are a useful solution to model them functionally. In this direction, several semantics exist and are at the core of metabolic network reconstruction, particularly for their refinement through gap-filling. Gap-filling is a combinatorial problem that aims at selecting reactions in databases to ensure the feasibility of a behaviour by the model. It is a very crucial step due to various pitfalls: model overfitting, false positive, choice of functionality semantics. This thesis aimed at better understand these limits and propose solutions to them. As a first results part, we benchmarked several gap-filling algorithms to assess the value of graph-based semantics with respect to the constraint based one. Then we propose a hybrid gap-filling method that reconciles both semantics. Finally, we extended the gap-filling problem towards the selection of communities and the screening of metabolic functions within large microbiotas. Problems modelled and solved during this PhD were applied to brown algae metabolism and to the human gut microbiota.

Software

Here is some computational biology software I developed or for which I was involved in the development:

2019
Metage2Metabo
Automatic metabolic network reconstruction with Pathway Tools and graph-based analysis of metabolic capabilities for the collection of networks, individually and collectively package, project
2018
MiSCoTO
Screening of microbiota metabolic capabilities and selection of minimal (minimal-size, minimal-exchanges) communities package, project
2017
AuReMe
Traceable and reproducible reconstruction of metabolic networks image, project ↗
2017
Fluto
Graph-based and constraint-based hybrid gap-filling of metabolic networks Conda package, project
2016
MeNeTools
Graph-based analysis tools for metabolic networks package, project
2015
Meneco
Graph-based gap-filling of metabolic networks package, project


Publications

Works ahead!

Some conference references and/or pdf may be missing.


  1. Bertille Burgunter-Delamare, Hetty KleinJan, Clémence Frioux, Enora Fremy, Margot Wagner, Erwan Corre, Alicia Le Salver, Cédric Leroux, Catherine Leblanc, Catherine Boyen, Anne Siegel, and Simon M. Dittami. Metabolic Complementarity Between a Brown Alga and Associated Cultivable Bacteria Provide Indications of Beneficial Interactions. Frontiers in Marine Science, 7 :85, 2020.

  2. Simon M. Dittami, Erwan Corre, Loraine Brillet-Guéguen, Agnieszka P. Lipinska, Noé Pontoizeau, Meziane Aite, Komlan Avia, Christophe Caron, Chung Hyun Cho, Jonas Collén, Alexandre Cormier, Ludovic Delage, Sylvie Doubleau, Clémence Frioux, Angélique Gobet, Irene González-Navarrete, Agnès Groisillier, Cécile Hervé, Didier Jollivet, Hetty KleinJan, Catherine Leblanc, Xi Liu, Dominique Marie, Gabriel V. Markov, André E. Minoche, Misharl Monsoor, Pierre Pericard, Marie Mathilde Perrineau, Akira F. Peters, Anne Siegel, Amandine Siméon, Camille Trottier, Hwan Su Yoon, Heinz Himmelbauer, Catherine Boyen, and Thierry Tonon. The genome of Ectocarpus subulatus – A highly stress-tolerant brown alga. Marine Genomics, :100740, 2020.

  3. Arnaud Belcour, Clémence Frioux, Méziane Aite, Anthony Bretaudeau, and Anne Siegel. Metage2Metabo: metabolic complementarity applied to genomes of large-scale microbiotas for the identification of keystone species, https://www.biorxiv.org/content/10.1101/803056v1?ct=, 2019.

  4. Delphine Nègre, Méziane Aite, Arnaud Belcour, Clémence Frioux, Loraine Brillet-Guéguen, Xi Liu, Philippe Bordron, Olivier Godfroy, Agnieszka P. Lipinska, Catherine Leblanc, Anne Siegel, Simon M. Dittami, Erwan Corre, and Gabriel V. Markov. Genome–scale metabolic networks shed light on the carotenoid biosynthesis pathway in the brown algae saccharina japonica and cladosiphon okamuranus. Antioxidants, 8(11) :564, 2019.

  5. Clémence Frioux, Torsten Schaub, Sebastian Schellhorn, Anne Siegel, and Philipp Wanko. Hybrid metabolic network completion. Theory and Practice of Logic Programming, 19(01) :83–108, 2019.

  6. Clémence Frioux, Enora Fremy, Camille Trottier, and Anne Siegel. Scalable and exhaustive screening of metabolic functions carried out by microbial consortia. Bioinformatics, 34(17) :i934–i943, 2018.

  7. Méziane Aite, Marie Chevallier, Clémence Frioux, Camille Trottier, Jeanne Got, María Paz Cortés, Sebastián N. Mendoza, Grégory Carrier, Olivier Dameron, Nicolas Guillaudeux, Mauricio Latorre, Nicolás Loira, Gabriel V. Markov, Alejandro Maass, and Anne Siegel. Traceability, reproducibility and wiki-exploration for “à-la-carte” reconstructions of genome-scale metabolic models. PLOS Computational Biology, 14(5) :1–25, 2018.

  8. Clémence Frioux. Investigating host-microbiota cooperation with gap-filling optimization problems, PhD thesis, Université de Rennes 1, November 2018.

  9. Clémence Frioux, Torsten Schaub, Sebastian Schellhorn, Anne Siegel, and Philipp Wanko. Hybrid metabolic network completion. In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), pp. 308–321, Springer, Cham, 2017.

  10. Julie Laniau, Clémence Frioux, Jacques Nicolas, Caroline Baroukh, María Paz Cortes, Jeanne Got, Camille Trottier, Damien Eveillard, and Anne Siegel. Combining graph and flux-based structures to decipher phenotypic essential metabolites within metabolic networks. PeerJ, 2017(10) 2017.

  11. Sylvain Prigent, Clémence Frioux, Simon M. Dittami, Sven Thiele, Abdelhalim Larhlimi, Guillaume Collet, Fabien Gutknecht, Jeanne Got, Damien Eveillard, Jérémie Bourdon, Frédéric Plewniak, Thierry Tonon, and Anne Siegel. Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks. PLoS Computational Biology, 13(1) 2017.

  12. Teemu Haikarainen, Clémence Frioux, Li-Qing Zhnag, Duo-Chuan Li, and Anastassios C. Papageorgiou. Crystal structure and biochemical characterization of a manganese superoxide dismutase from Chaetomium thermophilum. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1844(2) :422–429, 2014.


International

  1. Bertille Burgunter-Delamare, Hetty KleinJan, Clémence Frioux, Enora Fremy, Margot Wagner, Erwan Corre, Alicia Le Salver, Cédric Leroux, Catherine Leblanc, Catherine Boyen, Anne Siegel, and Simon M. Dittami. Metabolic Complementarity Between a Brown Alga and Associated Cultivable Bacteria Provide Indications of Beneficial Interactions. Frontiers in Marine Science, 7 :85, 2020.

  2. Simon M. Dittami, Erwan Corre, Loraine Brillet-Guéguen, Agnieszka P. Lipinska, Noé Pontoizeau, Meziane Aite, Komlan Avia, Christophe Caron, Chung Hyun Cho, Jonas Collén, Alexandre Cormier, Ludovic Delage, Sylvie Doubleau, Clémence Frioux, Angélique Gobet, Irene González-Navarrete, Agnès Groisillier, Cécile Hervé, Didier Jollivet, Hetty KleinJan, Catherine Leblanc, Xi Liu, Dominique Marie, Gabriel V. Markov, André E. Minoche, Misharl Monsoor, Pierre Pericard, Marie Mathilde Perrineau, Akira F. Peters, Anne Siegel, Amandine Siméon, Camille Trottier, Hwan Su Yoon, Heinz Himmelbauer, Catherine Boyen, and Thierry Tonon. The genome of Ectocarpus subulatus – A highly stress-tolerant brown alga. Marine Genomics, :100740, 2020.

  3. Clémence Frioux, Torsten Schaub, Sebastian Schellhorn, Anne Siegel, and Philipp Wanko. Hybrid metabolic network completion. Theory and Practice of Logic Programming, 19(01) :83–108, 2019.

  4. Delphine Nègre, Méziane Aite, Arnaud Belcour, Clémence Frioux, Loraine Brillet-Guéguen, Xi Liu, Philippe Bordron, Olivier Godfroy, Agnieszka P. Lipinska, Catherine Leblanc, Anne Siegel, Simon M. Dittami, Erwan Corre, and Gabriel V. Markov. Genome–scale metabolic networks shed light on the carotenoid biosynthesis pathway in the brown algae saccharina japonica and cladosiphon okamuranus. Antioxidants, 8(11) :564, 2019.

  5. Clémence Frioux, Enora Fremy, Camille Trottier, and Anne Siegel. Scalable and exhaustive screening of metabolic functions carried out by microbial consortia. Bioinformatics, 34(17) :i934–i943, 2018.

  6. Méziane Aite, Marie Chevallier, Clémence Frioux, Camille Trottier, Jeanne Got, María Paz Cortés, Sebastián N. Mendoza, Grégory Carrier, Olivier Dameron, Nicolas Guillaudeux, Mauricio Latorre, Nicolás Loira, Gabriel V. Markov, Alejandro Maass, and Anne Siegel. Traceability, reproducibility and wiki-exploration for “à-la-carte” reconstructions of genome-scale metabolic models. PLOS Computational Biology, 14(5) :1–25, 2018.

  7. Sylvain Prigent, Clémence Frioux, Simon M. Dittami, Sven Thiele, Abdelhalim Larhlimi, Guillaume Collet, Fabien Gutknecht, Jeanne Got, Damien Eveillard, Jérémie Bourdon, Frédéric Plewniak, Thierry Tonon, and Anne Siegel. Meneco, a Topology-Based Gap-Filling Tool Applicable to Degraded Genome-Wide Metabolic Networks. PLoS Computational Biology, 13(1) 2017.

  8. Julie Laniau, Clémence Frioux, Jacques Nicolas, Caroline Baroukh, María Paz Cortes, Jeanne Got, Camille Trottier, Damien Eveillard, and Anne Siegel. Combining graph and flux-based structures to decipher phenotypic essential metabolites within metabolic networks. PeerJ, 2017(10) 2017.

  9. Teemu Haikarainen, Clémence Frioux, Li-Qing Zhnag, Duo-Chuan Li, and Anastassios C. Papageorgiou. Crystal structure and biochemical characterization of a manganese superoxide dismutase from Chaetomium thermophilum. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1844(2) :422–429, 2014.

National


    International

    1. Clémence Frioux, Torsten Schaub, Sebastian Schellhorn, Anne Siegel, and Philipp Wanko. Hybrid metabolic network completion. In: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), pp. 308–321, Springer, Cham, 2017.

    National



        1. Clémence Frioux. Investigating host-microbiota cooperation with gap-filling optimization problems, PhD thesis, Université de Rennes 1, November 2018.


        1. Arnaud Belcour, Clémence Frioux, Méziane Aite, Anthony Bretaudeau, and Anne Siegel. Metage2Metabo: metabolic complementarity applied to genomes of large-scale microbiotas for the identification of keystone species, https://www.biorxiv.org/content/10.1101/803056v1?ct=, 2019.