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DYLISS - 2025

2025‌​‌Activity reportTeamDYLISS​​

RNSR: 201221035S
  • Research center​​​‌ Inria Centre at Rennes‌ University
  • In partnership with:‌​‌CNRS, Université de Rennes​​
  • Team name: Dynamics, Logics​​​‌ and Inference for biological‌ Systems and Sequences
  • In‌​‌ collaboration with:Institut de​​ recherche en informatique et​​​‌ systèmes aléatoires (IRISA)

Creation‌ of the Team: 2013‌​‌ July 01

Each year,​​ Inria research teams publish​​​‌ an Activity Report presenting‌ their work and results‌​‌ over the reporting period.​​ These reports follow a​​​‌ common structure, with some‌ optional sections depending on‌​‌ the specific team. They​​​‌ typically begin by outlining​ the overall objectives and​‌ research programme, including the​​ main research themes, goals,​​​‌ and methodological approaches. They​ also describe the application​‌ domains targeted by the​​ team, highlighting the scientific​​​‌ or societal contexts in​ which their work is​‌ situated.

The reports then​​ present the highlights of​​​‌ the year, covering major​ scientific achievements, software developments,​‌ or teaching contributions. When​​ relevant, they include sections​​​‌ on software, platforms, and​ open data, detailing the​‌ tools developed and how​​ they are shared. A​​​‌ substantial part is dedicated​ to new results, where​‌ scientific contributions are described​​ in detail, often with​​​‌ subsections specifying participants and​ associated keywords.

Finally, the​‌ Activity Report addresses funding,​​ contracts, partnerships, and collaborations​​​‌ at various levels, from​ industrial agreements to international​‌ cooperations. It also covers​​ dissemination and teaching activities,​​​‌ such as participation in​ scientific events, outreach, and​‌ supervision. The document concludes​​ with a presentation of​​​‌ scientific production, including major​ publications and those produced​‌ during the year.

Keywords​​

Computer Science and Digital​​​‌ Science

  • A3.1.1. Modeling, representation​
  • A3.1.2. Data management, quering​‌ and storage
  • A3.1.6. Query​​ optimization
  • A3.1.7. Open data​​​‌
  • A3.1.8. Big data (production,​ storage, transfer)
  • A3.1.11. Structured​‌ data
  • A3.2.1. Knowledge bases​​
  • A3.2.2. Knowledge extraction, cleaning​​​‌
  • A3.2.4. Semantic Web
  • A3.2.5.​ Ontologies
  • A3.4. Machine learning​‌ and statistics
  • A6.1.3. Discrete​​ Modeling (multi-agent, people centered)​​​‌
  • A7.3.1. Computational models and​ calculability
  • A9.1. Knowledge
  • A9.2.​‌ Machine learning

Other Research​​ Topics and Application Domains​​​‌

  • B1.1.2. Molecular and cellular​ biology
  • B1.1.4. Genetics and​‌ genomics
  • B1.1.7. Bioinformatics
  • B1.1.10.​​ Systems and synthetic biology​​​‌
  • B2.2.3. Cancer
  • B2.2.5. Immune​ system diseases

1 Team​‌ members, visitors, external collaborators​​

Research Scientists

  • Anne Siegel​​​‌ [Team leader,​ CNRS, Senior Researcher​‌, until Jun 2025​​, HDR]
  • Samuel​​​‌ Blanquart [INRIA,​ Researcher]
  • François Coste​‌ [INRIA, Researcher​​]
  • Anne Siegel [​​​‌CNRS, Senior Researcher​, from Jul 2025​‌, HDR]
  • Nathalie​​ Theret [INSERM,​​​‌ Senior Researcher, HDR​]

Faculty Members

  • Emmanuelle​‌ Becker [Team leader​​, UNIV RENNES,​​​‌ Professor, from Jul​ 2025, HDR]​‌
  • Emmanuelle Becker [UNIV​​ RENNES, Professor,​​​‌ until Jun 2025,​ HDR]
  • Catherine Belleannée​‌ [UNIV RENNES,​​ Associate Professor]
  • Myriam​​​‌ Bontonou [UNIV RENNES​, ATER, until​‌ Aug 2025]
  • Olivier​​ Dameron [UNIV RENNES​​​‌, Professor, HDR​]
  • Yann Le Cunff​‌ [UNIV RENNES,​​ Associate Professor, HDR​​​‌]

PhD Students

  • Moana​ Aulagner [INRIA]​‌
  • Cecile Beust [UNIV​​ RENNES]
  • Oceane Carpentier​​​‌ [UNIV RENNES]​
  • Elisa Chenel [UNIV​‌ RENNES]
  • Pablo Espana​​ Gutierrez [UNIV RENNES​​​‌]
  • Juliette Francis [​UNIV RENNES]
  • Pauline​‌ Giraud [UNIV RENNES​​]
  • Ulysse Le Clanche​​​‌ [UNIV RENNES]​
  • Corentin Lucas [INRIA​‌]
  • Noe Robert [​​UNIV RENNES, from​​​‌ Nov 2025]
  • Noryah​ Safla [INSERM,​‌ from Nov 2025]​​
  • Yael Tirlet [UNIV​​​‌ RENNES]

Technical Staff​

  • Jeanne Got [CNRS​‌, Engineer]
  • Alice​​ Mataigne [CNRS,​​ Engineer, until Jul​​​‌ 2025]
  • Noe Robert‌ [CNRS, Engineer‌​‌, until Jun 2025​​]

Interns and Apprentices​​​‌

  • Daniel Calvez [CNRS‌, Intern, from‌​‌ Apr 2025 until Jul​​ 2025]
  • Domenico Palladino​​​‌ [INRIA, Intern‌, from Nov 2025‌​‌]
  • Noryah Safla [​​INSERM, Intern,​​​‌ until Jul 2025]‌

Administrative Assistant

  • Marie Le‌​‌ Roïc [INRIA]​​

2 Overall objectives

Bioinformatics​​​‌ context: from life data‌ science to functional information‌​‌ about biological systems and​​ unconventional species. Sequence analysis​​​‌ and systems biology both‌ consist in the interpretation‌​‌ of biological information at​​ the molecular level, that​​​‌ concern mainly intra-cellular compounds.‌ Analyzing genome-level information is‌​‌ the main issue of​​ sequence analysis. The​​​‌ ultimate goal here is‌ to build a full‌​‌ catalogue of bio-products together​​ with their functions, and​​​‌ to provide efficient methods‌ to characterize such bio-products‌​‌ in genomic sequences. In​​ regards, contextual physiological information​​​‌ includes all cell events‌ that can be observed‌​‌ when a perturbation is​​ performed over a living​​​‌ system. Analyzing contextual physiological‌ information is the main‌​‌ issue of systems biology​​.

For a long​​​‌ time, computational methods developed‌ within sequence analysis and‌​‌ dynamical modeling had few​​ interplay. However, the emergence​​​‌ and the democratization of‌ new sequencing technologies (NGS,‌​‌ metagenomics) provides information to​​ link systems with genomic​​​‌ sequences. In this research‌ area, the Dyliss team‌​‌ focuses on linking genomic​​ sequence analysis and systems​​​‌ biology. Our main applicative‌ goal in biology is‌​‌ to characterize groups of​​ genetic actors that control​​​‌ the phenotypic response of‌ species when challenged by‌​‌ their environment. Our​​ main computational goals are​​​‌ to develop methods for‌ analyzing the dynamical response‌​‌ of a biological system,​​ modeling and classifying families​​​‌ of gene products with‌ sensitive and expressive languages,‌​‌ and identifying the main​​ actors of a biological​​​‌ system within static interaction‌ maps. We first‌​‌ formalize and integrate in​​ a set of logical​​​‌ or grammatical constraints both‌ generic knowledge information (literature-based‌​‌ regulatory pathways, diversity of​​ molecular functions, DNA patterns​​​‌ associated with molecular mechanisms)‌ and species-specific information (physiological‌​‌ response to perturbations, sequencing...).​​ We then rely on​​​‌ symbolic methods (Semantic Web‌ technologies for data integration,‌​‌ querying as well as​​ for reasoning with bio-ontologies,​​​‌ solving combinatorial optimization problems,‌ formal classification) to compute‌​‌ the main features of​​ the space of admissible​​​‌ models.

Computational challenges. The‌ main challenges we face‌​‌ are data incompleteness and​​ heterogeneity, leading to non-identifiability​​​‌. Indeed, we have‌ observed that the biological‌​‌ systems that we consider​​ cannot be uniquely identifiable.​​​‌ Indeed, "omics" technologies have‌ allowed the number of‌​‌ measured compounds in a​​ system to increase tremendously.​​​‌ However, it appears that‌ the theoretical number of‌​‌ different experimental measurements required​​ to integrate these compounds​​​‌ in a single discriminative‌ model has increased exponentially‌​‌ with respect to the​​ number of measured compounds.​​​‌ Therefore, according to the‌ current state of knowledge,‌​‌ there is no possibility​​ to explain the data​​​‌ with a single model.‌ Our rationale is that‌​‌ biological systems will still​​​‌ remain non-identifiable for a​ very long time. In​‌ this context, we favor​​ the construction and the​​​‌ study of a space​ of feasible models or​‌ hypotheses, including known​​ constraints and facts on​​​‌ a living system, rather​ than searching for a​‌ single discriminative optimized model.​​ We develop methods allowing​​​‌ a precise and exhaustive​ investigation of this space​‌ of hypotheses. With this​​ strategy, we are in​​​‌ the position of developing​ experimental strategies to progressively​‌ shrink the space of​​ hypotheses and increase the​​​‌ understanding of the system.​

Bioinformatics challenges. Our objectives​‌ in computer sciences are​​ developed within the team​​​‌ in order to fit​ with three main bioinformatics​‌ challenges (1) data-science and​​ knowledge-science for life sciences​​​‌ (see Section 3.2);​ (2) understanding metabolism (see​‌ Section 3.3); (3)​​ characterizing regulatory and signaling​​​‌ phenotypes (see Section 3.4​).

Implementing methods in​‌ software and platforms. Seven​​ platforms have been developed​​​‌ in the team during​ the last five years:​‌ Askomics, AuReMe, FinGoc, Caspo,​​ Cadbiom, Logol and Protomata.​​​‌ They aim at guiding​ the user to progressively​‌ reduce the space of​​ models (families of sequences​​​‌ of genes or proteins,​ families of keys actors​‌ involved in a system​​ response or dynamical models)​​​‌ which are compatible with​ both the knowledge and​‌ experimental observations. Most of​​ our platforms are developed​​​‌ with the support of​ the GenOuest resource and​‌ data center hosted in​​ the IRISA laboratory, including​​​‌ their computer facilities [More​ info]

3 Research program​‌

3.1 Context: Computer science​​ perspective on symbolic artificial​​​‌ intelligence

We develop methods​ that use an explicit​‌ representation of the relationships​​ between heterogeneous data and​​​‌ knowledge in order to​ construct a space of​‌ hypotheses. Therefore, our objective​​ in computer science is​​​‌ mainly to develop accurate​ representations (oriented graphs, Boolean​‌ networks, automata, or expressive​​ grammars) to iteratively capture​​​‌ the complexity of a​ biological system.

Integrating data​‌ with querying languages: Semantic​​ web for life sciences​​​‌ The first level of​ complexity in the data​‌ integration process consists in​​ confronting heterogeneous datasets. Both​​​‌ the size and the​ heretogeneity of life science​‌ data make their integration​​ and analysis by domain​​​‌ experts impractical and prone​ to the streetlight effect​‌ (they will pick up​​ the models that best​​​‌ match what they know​ or what they would​‌ like to discover). Our​​ first objective involves the​​​‌ formalization and management of​ symbolic knowledge, that is,​‌ the explicitation of relations​​ occurring in structured data.​​​‌ In this setting, our​ main goal is to​‌ facilitate and optimize the​​ integration of Semantic Web​​​‌ resources with local users​ data by relying on​‌ the implicit data scheme​​ contained in biological data​​​‌ and Semantic Web resources.​

Reasoning over structured data​‌ with constraint-based logical paradigms​​ Another level of complexity​​​‌ in life science integration​ is that very few​‌ paradigms exist to model​​ the behavior of a​​​‌ complex biological system. This​ leads biologists to perform​‌ and formulate hypotheses in​​ order to interpret their​​​‌ data. Our strategy is​ to interpret such hypotheses​‌ as combinatorial optimization problems,​​ allowing to reduce the​​ family of models compatible​​​‌ with data. To that‌ goal, we collaborate with‌​‌ Potsdam University in order​​ to use and challenge​​​‌ the most recent developments‌ of Answer Set Programming‌​‌ (ASP) 53, a​​ logical paradigm for solving​​​‌ constraint satisfiability and combinatorial‌ optimization issues.

Our goal‌​‌ is therefore to provide​​ scalable and expressive formal​​​‌ models of queries on‌ biological networks with the‌​‌ focus of integrating dynamical​​ information as explicit logical​​​‌ constraints in the modeling‌ process.

Characterizing biological sequences‌​‌ with formal syntactic models​​ Our last goal is​​​‌ to identify and characterize‌ the function of expressed‌​‌ genes such as transcripts,​​ enzymes or isoforms in​​​‌ non-model species biological networks‌ or specific functional features‌​‌ of metagenomic samples. These​​ are insufficiently precise because​​​‌ of the divergence of‌ biological sequences, the complexity‌​‌ of molecular structures and​​ biological processes, and the​​​‌ weak signals characterizing these‌ elements.

Our goal is‌​‌ therefore to develop accurate​​ formal syntactic models (automata,​​​‌ grammars or abstract gene‌ models) that would enable‌​‌ us to represent sequence​​ conservation, sets of short​​​‌ and degenerated patterns, and‌ crossing or distant dependencies.‌​‌ This requires both to​​ determine the classes of​​​‌ formal syntactic models adequate‌ for handling biological complexity,‌​‌ and to automatically characterize​​ the functional potential embodied​​​‌ in biological sequences with‌ these models.

3.2 Scalable‌​‌ methods to query data​​ heterogenity

Confronted to large​​​‌ and complex data sets‌ (raw data are associated‌​‌ with graphs depicting explicit​​ or implicit links and​​​‌ correlations) almost all scientific‌ fields have been impacted‌​‌ by the big data​​ issue, especially genomics​​​‌ and astronomy 65.‌ In our opinion, life‌​‌ sciences cumulate several features​​ that are very specific​​​‌ and prevent the direct‌ application of big data‌​‌ strategies that proved successful​​ in other domains such​​​‌ as experimental physics: the‌ existence of several scales‌​‌ of granularity (from microscopic​​ to macroscopic) and the​​​‌ associated issue of dependency‌ propagation, datasets incompleteness and‌​‌ uncertainty (including highly heterogeneous​​ responses to a perturbation​​​‌ from one sample to‌ another), and highly fragmented‌​‌ sources of information that​​ lacks interoperability 51.​​​‌ To explore this research‌ field, we use techniques‌​‌ from symbolic data mining​​ (Semantic Web technologies, symbolic​​​‌ clustering, constraint satisfaction, and‌ grammatical modeling) to take‌​‌ into account those life​​ science features in the​​​‌ analysis of biological data.‌

3.2.1 Research topics

Facilitating‌​‌ data integration and querying​​ The quantity and inner​​​‌ complexity of life science‌ data require semantically-rich analysis‌​‌ methods. A major challenge​​ is then to combine​​​‌ data (from local project‌ as well as from‌​‌ reference databases) and symbolic​​ knowledge seamlessly. Semantic Web​​​‌ technologies (RDF for annotating‌ data, OWL for representing‌​‌ symbolic knowledge, and SPARQL​​ for querying) provide a​​​‌ relevant framework, as demonstrated‌ by the success of‌​‌ Linked (Open) Data 33​​. However, life science​​​‌ end users (1) find‌ it difficult to learn‌​‌ the languages for representing​​ and querying Semantic Web​​​‌ data, and consequently (2)‌ miss the possibility they‌​‌ had to interact with​​ their tabulated data (even​​​‌ when doing so was‌ exceedingly slow and tedious).‌​‌ Our first objective in​​​‌ this axis is to​ develop accurate abstractions of​‌ datasets or knowledge repositories​​ to facilitate their exploration​​​‌ with RDF-based technologies.

Scalability​ of semantic web queries.​‌ A bottleneck in data​​ querying is given by​​​‌ the performance of federated​ SPARQL queries, which must​‌ be improved by several​​ orders of magnitude to​​​‌ allow current massive data​ to be analyzed. In​‌ this direction, our research​​ program focuses on the​​​‌ combination of linked data​ fragments  71, query​‌ properties and dataset structure​​ for decomposing federated SPARQL​​​‌ queries.

Building and compressing​ static maps of interacting​‌ compounds A final approach​​ to handle heterogeneity is​​​‌ to gather multi-scale data​ knowledge into a functional​‌ static map of biological​​ models that can be​​​‌ analyzed and/or compressed. This​ requires to link genomics,​‌ metabolomics, expression data and​​ protein measurement of several​​​‌ phenotypes into unified frameworks.​ In this direction, our​‌ main goal is to​​ develop families of constraints,​​​‌ inspired by symbolic dynamical​ systems, to link datasets​‌ together. We currently focus​​ on health (personalized medicine)​​​‌ and environmental (role of​ non-coding regulations, graph compression)​‌ datasets.

3.2.2 Associated software​​ tools

AskOmics platform AskOmics​​​‌ is an integration and​ interrogation software for linked​‌ biological data based on​​ semantic web technologies1​​​‌. AskOmics aims at​ bridging the gap between​‌ end user data and​​ the Linked (Open) Data​​​‌ cloud (LOD cloud). It​ allows heterogeneous bioinformatics data​‌ (formatted as tabular files​​ or directly in RDF)​​​‌ to be loaded into​ a Triple Store system​‌ using a user-friendly web​​ interface. It helps end​​​‌ users (1) to take​ advantage of the information​‌ available in the LOD​​ cloud for analyzing their​​​‌ own data, and (2)​ to contribute back to​‌ the linked data by​​ representing their data and​​​‌ the associated metadata in​ the proper format, as​‌ well as by linking​​ them to other resources.​​​‌ An originality is the​ graphical interface that allows​‌ any dataset to be​​ integrated in a local​​​‌ RDF datawarehouse and SPARQL​ query to be built​‌ transparently and iteratively by​​ a non-expert user.

Pax2graphml​​​‌ aims at easily manipulating​ BioPAX source files as​‌ regulated reaction graphs described​​ in graph format. The​​​‌ goal is to be​ highly flexible and to​‌ integrate graphs of regulated​​ reactions from a single​​​‌ BioPAX source or by​ combining and filtering BioPAX​‌ sources. The output graphs​​ can then be analyzed​​​‌ with additional tools developed​ in the team, such​‌ as KeyRegulatorFinder.

FinGoc-tools The​​ FinGoc tools allow filtering​​​‌ interaction networks with graph-based​ optimization criteria in order​‌ to elucidate the main​​ regulators of an observed​​​‌ phenotype. The main added-value​ of these tools is​‌ the functionality allowing to​​ make explicit the criteria​​​‌ used to highlight the​ role of the main​‌ regulators. (1) The KeyRegulatorFinder​​ package searches key regulators​​​‌ of lists of molecules​ (like metabolites, enzymes or​‌ genes) by taking advantage​​ of knowledge databases in​​​‌ cell metabolism and signaling​2. (2) The​‌ PowerGrasp python package implements​​ graph compression methods oriented​​​‌ toward visualization, and based​ on power graph analysis​‌3. (3) The​​ iggy package enables the​​ repairing of an interaction​​​‌ graph with respect to‌ expression data4.‌​‌

3.3 Metabolism: from protein​​ sequences to systems ecology​​​‌

Our research in bioinformatics‌ in relation with metabolic‌​‌ processes is driven by​​ the need to understand​​​‌ non-model (eukaryote) species. Their‌ metabolism have acquired specific‌​‌ features that we wish​​ to identify with computational​​​‌ methods. To that goal,‌ we combine sequence analysis‌​‌ with metabolic network analysis,​​ with the final goal​​​‌ to understand better the‌ metabolism of communities of‌​‌ organisms.

3.3.1 Research topics​​

Genomic level: characterizing functions​​​‌ of protein sequences Precise‌ characterization of functional proteins,‌​‌ such as enzymes or​​ transporters, is a key​​​‌ to better understand and‌ predict the actors involved‌​‌ in a metabolic process.​​ In order to improve​​​‌ the precision of functional‌ annotations, we develop machine‌​‌ learning approaches that take​​ a sample of functional​​​‌ sequences as input and‌ infer a model representing‌​‌ their key syntactical characteristics,​​ including dependencies between residues.​​​‌

System level: enriching and‌ comparing metabolic networks for‌​‌ non-model organisms

Non-model organisms​​ often lack both complete​​​‌ and reliable annotated sequences,‌ which cause the draft‌​‌ networks of their metabolism​​ to largely suffer from​​​‌ incompleteness. In former studies,‌ the team has developed‌​‌ several methods to improve​​ the quality of eukaryotic​​​‌ metabolic networks, by solving‌ several variants of the‌​‌ so-called Metabolic Network gap-filling​​ problem with logical programming​​​‌ approaches 10, 9‌. The main drawback‌​‌ of these approaches is​​ that they cannot scale​​​‌ to the reconstruction and‌ comparison of families of‌​‌ metabolic networks. Our main​​ objective is therefore to​​​‌ develop new tools for‌ the comparison of species‌​‌ strains at the metabolic​​ level.

Consortium level: exploring​​​‌ the diversity of community‌ consortia The newly emerging‌​‌ field of system ecology​​ aims at building predictive​​​‌ models of species interactions‌ within an ecosystem, with‌​‌ the goal of deciphering​​ cooperative and competitive relationships​​​‌ between species 50.‌ This field raises two‌​‌ new issues: (1) uncertainty​​ on the species present​​​‌ in the ecosystem and‌ (2) uncertainty about the‌​‌ global objective governing an​​ ecosystem. To address these​​​‌ challenges, our first research‌ focus is the inference‌​‌ of metabolic exchanges and​​ relationships for transporter identification,​​​‌ based on our expertise‌ in metabolic network gap-filling.‌​‌ The second challenging focus​​ is the prediction of​​​‌ transporters families via refined‌ characterization of transporters, which‌​‌ are quite unexplored apart​​ from specific databases 63​​​‌.

3.3.2 Associated software‌ tools

Protomata5 is‌​‌ a machine learning suite​​ for the inference of​​​‌ automata characterizing (functional) families‌ of proteins at the‌​‌ sequence level. It provides​​ programs to build a​​​‌ new kind of sequence‌ alignments (characterized as partial‌​‌ and local), learn automata,​​ and search for new​​​‌ family members in sequence‌ databases. By enabling to‌​‌ model local dependencies between​​ positions, automata are more​​​‌ expressive than classical tools‌ (PSSMs, Profile HMMs, or‌​‌ Prosite Patterns) and are​​ well suited to predict​​​‌ new family members with‌ a high specificity. This‌​‌ suite is for instance​​ embedded in the cyanolase​​​‌ database 40 to automate‌ its updade and was‌​‌ used for refining the​​​‌ classification of HAD enzymes​ 6 or identify shared​‌ conservations in the core​​ proteome of extracellular vesicles​​​‌ produced by human and​ animal S. aureus strains​‌ 68.

PPSuite6​​ is one of the​​​‌ first frameworks taking into​ account coevolutionary dependencies between​‌ residues for the comparison​​ of protein sequences. It​​​‌ proposes a complete workflow​ enabling to infer direct​‌ couplings between the positions​​ of a sequence of​​​‌ interest by a Potts​ model with the help​‌ of the sequence close​​ homologs and to score​​​‌ the similarity of the​ sequences by alignment of​‌ the inferred Potts models,​​ as well as tools​​​‌ to visualize the models​ and their alignments 67​‌, 66.

AuReMe​​ and AuCoMe workspaces is​​​‌ designed for tractable reconstruction​ of metabolic networks7​‌. The toolbox allows​​ for the Automatic Reconstruction​​​‌ of Metabolic networks based​ on the combination of​‌ multiple heterogeneous data and​​ knowledge sources 1.​​​‌ The main added values​ are the inclusion of​‌ graph-based tools relevant for​​ the study of non-model​​​‌ organisms (Meneco and Menetools​ packages), the possibility to​‌ trace the reconstruction and​​ curation procedures (Padmet package),​​​‌ and the exploration of​ reconstructed metabolic networks with​‌ wikis (wiki-export package, see:​​ aureme.genouest.org/wiki.html32.​​​‌ It also generates outputs​ to explore the resulting​‌ networks with Askomics. It​​ has been used for​​​‌ reconstructing metabolic networks of​ micro and macro-algae 61​‌, extremophile bacteria 43​​ and communities of organisms​​​‌ 4.

Mpwt, emmapper2gbk​ is a Python package​‌ for running Pathway Tools​​8 on multiple genomes​​​‌ using multiprocessing. Pathway Tools​ is a comprehensive systems​‌ biology software system that​​ is associated with the​​​‌ BioCyc database collection9​. Pathway Tools is​‌ frequently used for reconstructing​​ metabolic networks. In order​​​‌ to allow the output​ of the eggnoggmapper annotation​‌ tool to be used​​ by Mpwt, we also​​​‌ developed emmaper2gbk to create​ relevant genome files.

Metage2metabo​‌ is a Python tool​​ to perform graph-based metabolic​​​‌ analysis starting from annotated​ genomes (reference genomes or​‌ metagenome-assembled genomes) 30.​​ It uses Mpwt to​​​‌ reconstruct metabolic networks for​ a large number of​‌ genomes. The obtained metabolic​​ networks are then analyzed​​​‌ individually and collectively in​ order to get the​‌ added value of metabolic​​ cooperation in microbiota over​​​‌ individual metabolism and to​ identify and screen interesting​‌ organisms among all.

3.4​​ Regulation and signaling: detecting​​​‌ complex and discriminant signatures​ of phenotypes

On the​‌ contrary to metabolic networks,​​ regulatory and signaling processes​​​‌ in biological systems involve​ agents interacting at different​‌ granularity levels (from genes,​​ non-coding RNAs to protein​​​‌ complexes) and different time-scales.​ Our focus is on​‌ the reconstruction of large-scale​​ networks involving multiple scales​​​‌ processes, from which controllers​ can be extracted with​‌ symbolic dynamical systems methods.​​ Particular attention is paid​​​‌ to the characterization of​ products of genes (such​‌ as isoform) and of​​ perturbations to identify discriminant​​​‌ signature of pathologies.

3.4.1​ Research topics

Genomic level:​‌ characterizing gene structure with​​ grammatical languages and conservation​​​‌ information The goal here​ is to accurately represent​‌ gene structure, including intron/exon​​ structure, for predicting the​​ products of genes, such​​​‌ as isoform transcripts, and‌ comparing the expression potential‌​‌ of a eukaryotic gene​​ according to its context​​​‌ (e.g. tissue) or according‌ to the species. Our‌​‌ approach consists in designing​​ grammatical and comparative-genomics based​​​‌ models for gene structures‌ able to detect heterogeneous‌​‌ functional sites (splicing sites,​​ regulatory binding sites...), functional​​​‌ regions (exons, promotors...) and‌ global constraints (translation into‌​‌ proteins) 35. Accurate​​ gene models are defined​​​‌ by identifying general constraints‌ shaping gene families and‌​‌ their structures conserved over​​ evolution. Syntactic elements controlling​​​‌ gene expression (transcription factor‌ binding sites controlling transcription;‌​‌ enhancers and silencers controlling​​ splicing events...), i.e. short,​​​‌ degenerated and overlapping functional‌ sequences, are modeled by‌​‌ relying on the high​​ capability of SVG grammars​​​‌ to deal with structure‌ and ambiguity 64.‌​‌

System level: extracting causal​​ signatures of complex phenotypes​​​‌ with systems biology frameworks‌ Our main challenge is‌​‌ to set up a​​ generic formalism to model​​​‌ inter-layer interactions in large-scale‌ biological networks. To that‌​‌ goal, we have developed​​ several types of abstractions:​​​‌ multi-experiments framework to learn‌ and control signaling networks‌​‌ 11, multi-layer reactions​​ in interaction graphs 36​​​‌, and multi-layer information‌ in large-scale Petri nets‌​‌ 29. Our main​​ issues are to scale​​​‌ these approaches to standardized‌ large-scale repositories by relying‌​‌ on the interoperable Linked​​ Open Data (LOD) resources​​​‌ and to enrich them‌ with ad-hoc regulations extracted‌​‌ from sequence-based analysis. This​​ will allow us to​​​‌ characterize changes in system‌ attractors induced by mutations‌​‌ and how they may​​ be included in pathology​​​‌ signatures.

3.4.2 Associated software‌ tools

Logol software is‌​‌ designed for complex pattern​​ modeling and matching10​​​‌. It is a‌ swiss-army-knife for pattern matching‌​‌ on DNA/RNA/Protein sequences, based​​ on expressive patterns which​​​‌ consist in a complex‌ combination of motifs (such‌​‌ as degenerated strings) and​​ structures (such as imperfect​​​‌ stem-loop ou repeats) 2‌. Logol key features‌​‌ are the possibilities (i)​​ to divide a pattern​​​‌ description into several sub-patterns,‌ (ii) to model long‌​‌ range dependencies, and (iii)​​ to enable the use​​​‌ of ambiguous models or‌ to permit the inclusion‌​‌ of negative conditions in​​ a pattern definition. Therefore,​​​‌ Logol encompasses most of‌ the features of specialized‌​‌ tools (Vmatch, Patmatch, Cutadapt,​​ HMM) and enables interplays​​​‌ between several classes of‌ patterns (motifs and structures),‌​‌ including stem-loop identification in​​ CRISPR.

Caspo Cell ASP​​​‌ Optimizer (Caspo)‌ software constitutes a pipeline‌​‌ for automated reasoning on​​ logical signaling networks (learning,​​​‌ classifying, designing experimental perturbations,‌ identifying controllers, take time-series‌​‌ into account)11.​​ The software handles inherent​​​‌ experimental noise by enumerating‌ all different logical networks‌​‌ which are compatible with​​ a set of experimental​​​‌ observations 11. The‌ main advantage is that‌​‌ it enables a complete​​ study of logical network​​​‌ without requiring any linear‌ constraint programs.

Cadbiom package‌​‌ aims at building and​​ analyzing the asynchronous dynamics​​​‌ of enriched logical networks‌12. It is‌​‌ based on Guarded transition​​ semantic and allows synchronization​​​‌ events to be investigated‌ in large-scale biological networks‌​‌ 29. For example,​​​‌ it allowed to analyze​ controler of phenotypes in​‌ a large-scale knowledge database​​ (PID) 5.

Recently,​​​‌ we have significantly refactored​ Cadbiom package towards a​‌ framework that allows the​​ identification of causal regulators​​​‌ in large-scale models, formalized​ in the BioPAX language​‌ and automatically interpreted as​​ guarded transitions. The Cadbiom​​​‌ framework was applied to​ the BioPAX version of​‌ two ressources (PID, KEGG)​​ of the PathwayCommons database​​​‌ and to the Atlas​ of Cancer Signalling Network​‌ (ACSN). As a case-study,​​ it was used to​​​‌ characterize the causal signatures​ of markers of the​‌ epithelial-mesenchymal transition.

4 Application​​ domains

In terms of​​​‌ transfer and societal impact,​ we consider that our​‌ role is to develop​​ fruitful collaborations with biology​​​‌ laboratories in order to​ consolidate their studies by​‌ a smart use of​​ our tools and prototypes​​​‌ and to generate new​ biological hypotheses to be​‌ tested experimentally.

Marine Biology:​​ seaweed enzymes and metabolism​​​‌ An important field of​ study is marine biology​‌, as it is​​ a transversal field covering​​​‌ challenges in integrative biology,​ dynamical systems and sequence​‌ analysis.

  • Protein functions in​​ seaweed metabolism Several years​​​‌ ago, our methods based​ on combinatorial optimization for​‌ the reconstruction of genome-scale​​ metabolic networks and on​​​‌ classification of enzyme families​ based on local and​‌ partial alignments allowed the​​ seaweed E. siliculosus metabolism​​​‌ to be deciphered 61​, 44. The​‌ study of the HAD​​ superfamily of proteins thanks​​​‌ to partial local alignments​ produced by Protomata tools,​‌ allowed sub-families to be​​ deciphered and classified. Additionally,​​​‌ the metabolic map reconstructed​ with Meneco enabled the​‌ reannotation of 56 genes​​ within the E. siliculosus​​​‌ genome. These approaches also​ shed light on evolution​‌ of metabolic processes.
  • Elucidating​​ algal metabolism thanks to​​​‌ large-scale metabolic network reconstructions​ More recently, the tools​‌ developed by Dyliss (based​​ on the AuReMe toolbox)​​​‌ allowed us to participate​ in the reconstruction of​‌ a metabolic network for​​ the brown algae Saccharina​​​‌ japonica and Cladosiphon okamuranus​ in order to identify​‌ these species specificities on​​ the synthesis of carotenoids​​​‌ biosynthesis 59. We​ also participated in the​‌ study of the genome​​ of Ectocarpus subulatus,​​​‌ a highly stress-tolerant algal​ strain 49. Finally,​‌ AuReMe has been used​​ to analyze the metabolic​​​‌ capacity of several strains​ of cyanobacteria, with results​‌ integrated in the Cyanorak​​ database 52 and to​​​‌ characterize synergistic effects of​ the synechococcus strain WH7803​‌ 55.
  • Metabolic pathway​​ drift theory Genome annotations​​​‌ can contribute to understanding​ algal metabolism. The tool​‌ PathModel was developed to​​ add support for biochemical​​​‌ reactions and metabolite structures​ to the theory of​‌ metabolic pathway drift with​​ an approach combining chemoinformatics​​​‌ knowledge reasoning and modeling.​ This approach was applied​‌ to the study of​​ the red alga Chondrus​​​‌ crispus, which allowed​ to show that even​‌ for metabolic pathways supposed​​ to be conserved between​​​‌ species (sterols, mycrosporins synthesis),​ we can see an​‌ important turnover in the​​ order of reactions appearing​​​‌ in a metabolic pathway.​ This work lays the​‌ foundations for the concept​​ of "metabolic drift" analogous​​ to the same concept​​​‌ in genomics. 31.‌
  • Algal-bacteria interactions We reconstructed‌​‌ the metabolic network of​​ a symbiot bacterium Ca.​​​‌ P. ectocarpi 48 and‌ used this reconstructed network‌​‌ to decipher interactions within​​ the algal-bacteria holobiont, revealing​​​‌ several candidates metabolic pathways‌ for algal-bacterial interactions. Similarily,‌​‌ our analyses suggested that​​ the bacterium Ca. P.​​​‌ ectocarpi is able to‌ provide both beta-alanine and‌​‌ vitamin B5 to the​​ seaweed via the phosphopantothenate​​​‌ biosynthesis pathway 62.‌

    These works paved the‌​‌ way to the study​​ of host-microbial interactions, as​​​‌ shown in 41 where‌ we evidenced the role‌​‌ of tools such as​​ miscoto and metage2metabo to​​​‌ predict synthetic communities allowing‌ to restore algal metabolic‌​‌ pathways. To validate these​​ approaches experimentally, we worked​​​‌ with S. Dittami, researcher‌ at the Roscoff biological‌​‌ station. We applied these​​ methods on a set​​​‌ of about fifteen cultivable‌ bacteria identified on the‌​‌ wall membrane of Ectocarpus​​ siliculosus. Our approaches​​​‌ predicted that three bacteria‌ were necessary to facilitate‌​‌ the growth of this​​ alga in an axenic​​​‌ medium. The experiments were‌ carried out, and indeed‌​‌ allowed the alga to​​ grow in an axenic​​​‌ medium. This is therefore‌ a proof of concept‌​‌ of the relevance of​​ our approaches. More recently,​​​‌ the study of the‌ freshwater strain of Ectocarpus‌​‌ subulatus evidenced the role​​ of metabolism in adaptation,​​​‌ paving the way to‌ biotechnological applications 57.‌​‌

Microbiology: elucidating the functioning​​ of extremophile consortiums of​​​‌ bacteria. Our main issue‌ is the understanding of‌​‌ bacteria living in extreme​​ environments. The context is​​​‌ mainly a collaboration with‌ the group of bioinformatics‌​‌ at Universidad de Chile​​ (co-funded by the Center​​​‌ of Mathematical Modeling, the‌ Center of Regulation Genomics‌​‌ and Inria-Chile). In order​​ to elucidate the main​​​‌ characteristics of these bacteria,‌ our integrative methods were‌​‌ developed to identify the​​ main groups of regulators​​​‌ for their specific response‌ in their living environment.‌​‌ The integrative biology tools​​ Meneco, Lombarde and​​​‌ Shogen have been designed‌ in this context. In‌​‌ particular, genome-scale metabolic network​​ been recently reconstructed and​​​‌ studied with the Meneco‌ and Shogen approaches, especially‌​‌ on bacteria involved in​​ biomining processes 37 and​​​‌ in Salmon pathogenicity 43‌. We have also‌​‌ studied the specificities of​​ two Microbacterium strains, CGR1​​​‌ and CGR2, isolated in‌ different soils of the‌​‌ Atacama Desert in Chile,​​ showing significant differences on​​​‌ the connectivity of metabolite‌ production in relation to‌​‌ pH tolerance and CO2​​ production 58.

Agriculture​​​‌ and environmental sciences: upstream‌ controllers of cow, pork‌​‌ and pea-aphid metabolism and​​ regulation. Our goal is​​​‌ to propose methods to‌ identify regulators of complex‌​‌ phenotypes related to environmental​​ issues. Our work on​​​‌ the identification of upstream‌ regulators within large-scale knowledge‌​‌ databases (tool KeyRegulatorFinder)​​ 36 and on semantic-based​​​‌ analysis of metabolic networks‌ 34 was very valuable‌​‌ for interpreting the differences​​ of gene expression in​​​‌ pork meat 56 and‌ figure out the main‌​‌ gene-regulators of the response​​ of porks to several​​​‌ diets 54. Our‌ expertise in microbiota analysis‌​‌ is also currently being​​​‌ applied to rumen microbial​ genomics 60.

Health:​‌ Dynamics of microenvironment in​​ chronic liver diseases We​​​‌ develop methods and models​ to understand the dynamics​‌ of the microenvironment in​​ order to propose evolutionary​​​‌ markers and effective therapeutic​ targets. The matrix microenvironment​‌ is the major regulator​​ of events related to​​​‌ fibrosis-cirrhosis-cancer progression and Hepatic​ Stellate Cells (HSC) are​‌ the main actors of​​ microenvironment remodeling. At molecular​​​‌ level, the transforming growth​ factor TGF-β plays​‌ a central role by​​ promoting HSC activation, extracellular​​​‌ matrix remodeling and epithelial-mesenchymal​ transition. In that context​‌ we have developed three​​ programs :

  • TGF-β​​​‌ signaling networks. TGF-​β is a multifunctional​‌ cytokine that binds to​​ specific receptors and induce​​​‌ numerous signaling pathways depending​ on the context. Deciphering​‌ TGF-β signaling networks​​ requires to take into​​​‌ account a system-wide view​ and develop predictive models​‌ for therapeutic benefit. For​​ that purpose we developed​​​‌ Cadbiom and identified gene​ networks associated with innate​‌ immune response to viral​​ infection that combine TGF-​​​‌β and interleukin signaling​ pathways 29, 42​‌. More recently we​​ have very significantly refactored​​​‌ Cadbiom package towards a​ framework that allows the​‌ identification of causal regulators​​ in large-scale models, formalized​​​‌ in the BioPAX language​ and automatically interpreted as​‌ guarded transitions13.The​​ Cadbiom framework was applied​​​‌ to the BioPAX version​ of two resources (PID,KEGG)​‌ of the Pathway Commons​​ database and to the​​​‌ Atlas of Cancer Signalling​ Network (ACSN). As a​‌ case-study, it was used​​ to characterize the causal​​​‌ signatures of markers of​ the epithelial-mesenchymal transition.
  • Functional​‌ signature for ADAMTS.​​ Hepatic Stellate Cells produce​​​‌ a wide variety of​ molecules involved in ECM​‌ remodeling, such as adamalysins​​ 69. However, the​​​‌ limitations of discovering new​ functions of these proteins​‌ stem from the experimental​​ approaches that are difficult​​​‌ to implement due to​ their structure and biochemical​‌ features. In that context​​ we developed an original​​​‌ framework combining the identification​ of small modules in​‌ conserved regions independent of​​ known domains and the​​​‌ concepts of phylogenomics (association​ of conservation and phenotype​‌ gained concurrently during evolution).​​ The resulting evolutionary model​​​‌ of motif signatures and​ protein-protein interaction signatures of​‌ the ADAMTS family is​​ validated by data from​​​‌ literature and provides biologists​ with many new potential​‌ functional motifs 46,​​ 4547.​​​‌
  • Dynamic model of hepatic​ stellate cells. To​‌ characterize the dynamics of​​ HSC activation upon TGFB1​​​‌ stimulation, we developed a​ model using Kappa, a​‌ site graph rewriting language​​ and its static analyzer​​​‌ Kasa 39. We​ previously demonstrated the advantages​‌ of Kappa language for​​ modeling TGF-β signaling​​​‌ and extracellular matrix 70​. Unlike previous model​‌ based on a population​​ of interacting proteins, we​​​‌ now develop an original​ Kappa model based on​‌ a population of cells​​ interacting with TGF-β​​​‌ 38. The model​ recapitulates the dynamics of​‌ activation of HSC towards​​ myofibroblast states and the​​​‌ reversion processes. Current work​ aims to identify the​‌ regulators of the repair​​ likely to promote the​​ resolution of fibrosis at​​​‌ the expense of its‌ progression.

5 Social and‌​‌ environmental responsibility

5.1 Footprint​​ of research activities

Our​​​‌ footprint for 2025 is‌ 6.8T CO2 for the‌​‌ entire team. This is​​ mainly driven by 3​​​‌ transatlantic missions (2 long‌ missions 2-3 weeks to‌​‌ see our collaborators in​​ Chile, and 1 mission​​​‌ of 1 week in‌ Chicago). For other missions‌​‌ in France and Switzerland​​ (between 40 and 50),​​​‌ we favored train (0T‌ CO2), except for one‌​‌ mission to Paris and​​ another to Nantes by​​​‌ car (0.2T CO2, calculated‌ on the ADEME website).‌​‌ For PhD juries ouside​​ France (Canada), we opted​​​‌ for videoconferencing.

Outside missions,‌ Dyliss research activities have‌​‌ low environmental footprints. Most​​ of our software solution​​​‌ run on off-the-shelf computers‌ and are not computationally‌​‌ intensive. Indirectly, the analyses​​ and predictions we make​​​‌ intend to reduce the‌ need for long, costly‌​‌ technically or ethically difficult​​ biological experiments.

5.2 Impact​​​‌ of research results

Through‌ our ongoing collaborations with‌​‌ INSERM and Rennes' Hospital,​​ Dyliss research activities have​​​‌ a social impact on‌ human health. Our collaborations‌​‌ with INRAe have a​​ direct impact on vegetal​​​‌ and animal health, and‌ an indirect impact in‌​‌ environment as these projects​​ original motivation is to​​​‌ reduce fertilizers or pesticides.‌

6 Highlights of the‌​‌ year

In 2025, in​​ accordance with the operating​​​‌ principle of INRIA project‌ teams, which have a‌​‌ limited lifespan, the DYLISS​​ team actively prepared for​​​‌ its future evolution. A‌ request to create a‌​‌ future team was submitted​​ and accepted (future BioGraphs​​​‌ team).

6.1 Members

  • Yann‌ Le Cunff successfully defended‌​‌ his habilitation, entitled “From​​ Data to Phenotype: Integrating​​​‌ Data Structure and Prior‌ Knowledge to Model Biological‌​‌ Systems” in May 2025.​​
  • Samuel Blanquart was promoted​​​‌ to CRHC.
  • Jeanne Got‌ was promoted to IEHC.‌​‌

6.2 Broadening International Visibility​​

Yaël Tirlet , PhD​​​‌ student in the DYLISS‌ team, has been awarded‌​‌ by the doctoral school​​ a fellowship for a​​​‌ mobility in Switzerland (3‌ months), to start a‌​‌ collaboration with the Swiss​​ Institute of Bioinformatics. The​​​‌ mobility allowed to start‌ a fruitful collaboration with‌​‌ Jerven Bolleman involving other​​ members of the DYLISS​​​‌ team Olivier Dameron ,‌ Emmanuelle Becker (publications submitted).‌​‌

Cécile Beust , PhD​​ student in the DYLISS​​​‌ team, has been awarded‌ by the doctoral school‌​‌ a fellowship for a​​ mobility in the U.S.​​​‌ (UC San Diego, California)‌ to start a collaboration‌​‌ with the Cytoscape team​​ (2 months), but was​​​‌ unable to move to‌ the U.S. at the‌​‌ proposed period because of​​ the U.S. administration's visa​​​‌ blocking policy in June‌ 2025. The visit was‌​‌ thus replaced by a​​ remote collaboration involving other​​​‌ members of the DYLISS‌ team Emmanuelle Becker ,‌​‌ Olivier Dameron and Nathalie​​ Theret .

7 Latest​​​‌ software developments, platforms, open‌ data

7.1 Latest software‌​‌ developments

7.1.1 AskOmics

  • Name:​​
    Convert tabulated data into​​​‌ RDF and create SPARQL‌ queries intuitively and "on‌​‌ the fly".
  • Keywords:
    RDF,​​ SPARQL, Querying, Graph, LOD​​​‌ - Linked open data‌
  • Functional Description:
    AskOmics aims‌​‌ at bridging the gap​​​‌ between end user data​ and the Linked (Open)​‌ Data cloud. It allows​​ heterogeneous bioinformatics data (formatted​​​‌ as tabular files) to​ be loaded in a​‌ RDF triplestore and then​​ be transparently and interactively​​​‌ queried. AskOmics is made​ of three software blocks:​‌ (1) a web interface​​ for data import, allowing​​​‌ the creation of a​ local triplestore from user's​‌ datasheets and standard data,​​ (2) an interactive web​​​‌ interface allowing "à la​ carte" query-building, (3) a​‌ server performing interactions with​​ local and distant triplestores​​​‌ (queries execution, management of​ users parameters).
  • URL:
  • Contact:
    Olivier Dameron
  • Partners:​​
    Université de Rennes 1,​​​‌ CNRS, INRA

7.1.2 Metage2Metabo​

  • Keywords:
    Metabolic networks, Microbiota,​‌ Metagenomics, Workflow
  • Scientific Description:​​
    Flexible pipeline for the​​​‌ metabolic screening of large​ scale microbial communities described​‌ by reference genomes or​​ metagenome-assembled genomes. The pipeline​​​‌ comprises several main steps.​ (1) Automatic and parallel​‌ reconstruction of metabolic networks.​​ (2) Computation of individual​​​‌ metabolic potentials (3) Computation​ of collective metabolic potential​‌ (4) Calculation of the​​ cooperation potential described as​​​‌ the set of metabolites​ producible by species only​‌ in a cooperative context​​ (5) Computation of minimal-sized​​​‌ communities sastifying a metabolic​ objective (6) Extraction of​‌ key species (essential and​​ alternative symbionts) associated to​​​‌ a metabolic function
  • Functional​ Description:
    Metabolic networks are​‌ graphs which nodes are​​ compounds and edges are​​​‌ biochemical reactions. To study​ the metabolic capabilities of​‌ microbiota, Metage2Metabo uses multiprocessing​​ to reconstruct metabolic networks​​​‌ at large-scale. The individual​ and collective metabolic capabilities​‌ (number of compounds producible)​​ are computed and compared.​​​‌ From these comparisons, a​ set of compounds only​‌ producible by the community​​ is created. These newly​​​‌ producible compounds are used​ to find minimal communities​‌ that can produce them.​​ From these communities, the​​​‌ keystone species in the​ production of these compounds​‌ are identified.
  • URL:
  • Publication:
  • Contact:
    Clemence​​​‌ Frioux
  • Participants:
    Clemence Frioux,​ Arnaud Belcour, Anne Siegel​‌

7.1.3 AuCoMe

  • Name:
    Automatic​​ Comparison of Metabolisms
  • Keywords:​​​‌
    Bioinformatics, Workflow, Metabolic networks,​ Omic data, Data analysis​‌
  • Functional Description:
    AuCoMe is​​ a Python package that​​​‌ aims at reconstructing homogeneous​ metabolic networks and pan-metabolism​‌ starting from genomes with​​ heterogeneous levels of annotations.​​​‌ Four steps are composing​ AuCoMe. 1) It automatically​‌ infers annotated genomes from​​ draft metabolic networks thanks​​​‌ to Pathway Tools and​ MPWT. 2) The Gene-Protein-Reaction​‌ (GPR) associations previously obtained​​ are propagated to protein​​​‌ orthogroups in using Orthofinder​ and, an additional robustness​‌ criteria. 3) AuCoMe checking​​ the presence of supplementary​​​‌ GPR associations by finding​ missing annotation in all​‌ genomes. In this step,​​ the tools BlastP, TblastN​​​‌ and, Exonerate are called.​ 4) It adding spontaneous​‌ reactions to metabolic pathways​​ that were completed by​​​‌ the previous steps. AuCoMe​ generates several outputs to​‌ facilitate the analysis of​​ results: tabuled files, SBML​​​‌ files, PADMET files, supervenn​ and a dendogram of​‌ reactions.
  • URL:
  • Publication:​​
  • Contact:
    Anne Siegel​​​‌
  • Participants:
    Arnaud Belcour, Jeanne​ Got, Meziane Aite, Ludovic​‌ Delage, Jonas Collen, Clemence​​ Frioux, Catherine Leblanc, Simon​​​‌ M. Dittami, Samuel Blanquart,​ Gabriel V. Markov, Anne​‌ Siegel

7.1.4 prolipipe

  • Keywords:​​
    Metabolic networks, Workflow, Bacterial​​ strains
  • Scientific Description:
    This​​​‌ pipeline evaluates in silico‌ the ability of several‌​‌ thousand bacteria to produce​​ specific metabolites. (1) Reconstruction​​​‌ of large-scale metabolic networks‌ using three annotation software‌​‌ programs, thanks to the​​ AuFAMe tool (https://github.com/AuReMe/AuFAMe). (2)​​​‌ Analysis of the synthesis‌ pathways producing specific metabolites‌​‌ in the bacterial metabolic​​ networks created. (3) Generation​​​‌ of a heatmap for‌ each synthesis pathway studied.‌​‌ (4) Production of a​​ SPARQL-queryable file to easily​​​‌ exploit the results produced.‌
  • Functional Description:
    This pipeline‌​‌ evaluates in silico the​​ ability of several thousand​​​‌ bacteria to produce specific‌ compounds. Prolipipe generates bacterial‌​‌ metabolic networks from their​​ genomes. By focusing on​​​‌ certain synthesis pathways chosen‌ by the user, it‌​‌ will create as many​​ heatmaps as there are​​​‌ synthesis pathways studied. The‌ metabolic specifications of each‌​‌ bacterium will be visualized​​ on these heatmaps. Prolipipe​​​‌ also generates an easily‌ queryable file.
  • News of‌​‌ the Year:
    With this​​ software, we obtained a​​​‌ PCI recommendation in 2025‌ and are currently in‌​‌ the process of publishing​​ it.
  • URL:
  • Publication:​​​‌
  • Contact:
    Noe Robert‌
  • Participants:
    Noe Robert, Jeanne‌​‌ Got, Pauline Giraud, Hélène​​ Falentin, Anne Siegel
  • Partner:​​​‌
    INRAE

7.1.5 EnzBert-GO

  • Keywords:‌
    Proteins, Biological sequences, Functional‌​‌ annotation, Deep learning, Ontologies​​
  • Scientific Description:
    Code for​​​‌ learning and using BERT‌ deep neural architectures for‌​‌ the prediction of multi-level​​ and multi-class functional enzymatic​​​‌ GO (Gene Ontology) annotations‌ of protein sequences.
  • Functional‌​‌ Description:
    Prediction of the​​ functional enzymatic GO annotations​​​‌ of protein sequences
  • News‌ of the Year:
    EnzBert-GO‌​‌ has been generalized to​​ support hierarchical labels beyond​​​‌ those from Gene Ontology.‌ This includes expert refinements‌​‌ of Gene Ontology, Enzyme​​ Commission numbers, and others.​​​‌
  • URL:
  • Contact:
    François‌ Coste
  • Participant:
    François Coste‌​‌

7.1.6 FUSE-PhyloTree

  • Name:
    FUnctions​​ and SEquence conservations on​​​‌ a Phylogenetic Tree
  • Keywords:‌
    Bioinformatics, Biological sequences, Sequence‌​‌ alignment, Phylogenomics, Proteins
  • Scientific​​ Description:
    FUSE-PhyloTree is dedicated​​​‌ to estimate the sequence‌ regions which are potentially‌​‌ associated to functions of​​ interest in a multi-functional​​​‌ protein families, such as‌ paralogous and multi-domain protein‌​‌ families. The method uses​​ state-of -the-art programs to​​​‌ estimate a mapping of‌ both the ancestral functions‌​‌ and the ancestral sequence​​ content at each node​​​‌ in the phylogenetic family‌ tree. It enables the‌​‌ association of functions with​​ local sequence conservations through​​​‌ the inference of their‌ co-appearance along the evolutionary‌​‌ gene tree, and it​​ generates interactive Itol representations​​​‌ allowing to explore the‌ annotated tree.
  • Functional Description:‌​‌
    FUSE-PhyloTree takes as input:​​ 1) protein sequences of​​​‌ the target family (including‌ both paralogs and orthologs),‌​‌ 2) a gene tree​​ corresponding to these sequences,​​​‌ and 3) functional annotations‌ of interest of proteins,‌​‌ for instance their identified​​ protein-protein interactions (PPI). As​​​‌ a result, FUSE-PhyloTree provides‌ a gene tree annotated‌​‌ with both predicted conserved​​ sequence modules and functions​​​‌ of ancestral genes, enabling‌ the association of functions‌​‌ with specific sequence regions​​ based on their co-emergence​​​‌ during gene evolution.
  • News‌ of the Year:
    The‌​‌ primary improvement in the​​ software is the introduction​​​‌ of an estimate for‌ the robustness of predictions‌​‌ regarding the appearance of​​​‌ modules in ancestral genes.​ This allows users to​‌ prioritize stronger predictions while​​ still retaining weaker ones​​​‌ for consideration. In addition,​ the update includes general​‌ improvements to the user​​ experience, enhanced documentation, and​​​‌ has been published as​ an Application Note in​‌ Bioinformatics.
  • URL:
  • Publications:​​
  • Contact:​​​‌
    François Coste
  • Participants:
    Olivier​ Dennler, Elisa Chenel, François​‌ Coste, Samuel Blanquart, Catherine​​ Belleannée, Nathalie Theret

8​​​‌ New results

8.1 Scalable​ methods to query data​‌ heterogeneity

Participants: Emmanuelle Becker​​, Cécile Beust,​​​‌ Océane Carpentier, Olivier​ Dameron, Ulysse Le​‌ Clanche, Yann Le​​ Cunff, Alice Mataigne​​​‌, Anne Siegel,​ Nathalie Théret, Yael​‌ Tirlet.

ACUITEE: A​​ Comprehensive Tool for Visualization,​​​‌ Editing and Curating textual​ Annotations in Clinical Data​‌ [Olivier Dameron ]​​ 18 Annotation and management​​​‌ of clinical data remains​ a critical but challenging​‌ task due to the​​ complexity and diversity of​​​‌ medical records. We developed​ ACUITEE (Annotation and Curation​‌ User Interface for Terms​​ Extraction Engines), a web​​​‌ application that offers a​ simple way to improve​‌ clinical data annotation workflows​​ by integrating automatic analysis,​​​‌ manual processing, and real-time​ visualization of medical notes.​‌ Using advanced natural language​​ processing (NLP) techniques for​​​‌ phenotypes extraction such as​ PhenoBERT and efficient string-matching​‌ algorithms, ACUITEE maps free-text​​ medical notes to ontology​​​‌ terms and enables clinicians​ to validate or refine​‌ these annotations through a​​ user-friendly interface. The system​​​‌ supports fully automated, semi-automated​ and manual annotation modes,​‌ providing flexibility for different​​ use cases. A key​​​‌ feature of ACUITEE is​ its interactive annotation interface,​‌ which enables clinicians to​​ validate, edit, and curate​​​‌ ontology terms with precision,​ thereby speeding up the​‌ annotation process while maintaining​​ high accuracy.

Biological Knowledge​​​‌ Extraction from BioPAX Graphs​ [Emmanuelle Becker ,​‌ Cécile Beust , Olivier​​ Dameron , Nathalie Théret​​​‌ ] 25 In systems​ biology, the study of​‌ biological pathways is a​​ key to understand the​​​‌ complexity of biological systems.​ The recent massification of​‌ biological pathway data available​​ online through various databases​​​‌ raised an important need​ of standardization of these​‌ data. The BioPAX format​​ (Biological Pathway Exchange), created​​​‌ in 2010, is a​ semantic web format designed​‌ for the standardization and​​ exchange of pathway data.​​​‌ BioPAX is highly expressive​ but intrinsically complex, limiting​‌ its wider adoption. We​​ reported on the use​​​‌ of the BioPAX format​ in 2024 and present​‌ abstraction methods to simplify​​ knowledge extraction from BioPAX​​​‌ graphs.

Assessing bioinformatics software​ annotations: bio.tools case-study [​‌Olivier Dameron , Ulysse​​ Le Clanche , Yann​​​‌ Le Cunff ] 20​ Reproducibility and reuse of​‌ digital bioinformatics resources are​​ essential for the development​​​‌ of open and cumulative​ science, in line with​‌ FAIR principles. To search​​ and reuse bioinformatics tools,​​​‌ scientists need to be​ confident enough with the​‌ reliability of their annotations.​​ Our study focuses on​​​‌ the quantitative and qualitative​ evaluation of semantic annotations​‌ in the bio.tools registry,​​ which serves more than​​​‌ 30,000 bioinformatics tool descriptions,​ annotated with the EDAM​‌ ontology. In this work​​ we propose to study​​ how the EDAM ontology​​​‌ is used to categorize‌ software based on scientific‌​‌ disciplines and the kind​​ of data processing they​​​‌ allow. We also evaluate‌ how qualitative are the‌​‌ annotations based on Shannon​​ entropy. We emphasize that​​​‌ a particular attention should‌ be given to the‌​‌ whole set of inherited​​ annotations, from the used​​​‌ ontology. Our results underline‌ the need for automatic‌​‌ tools to support annotation​​ curation, reducing the annotation​​​‌ cost for domain experts.‌ This study is a‌​‌ preliminary work aimed at​​ designing novel annotation approaches​​​‌ based on the combination‌ of knowledge graphs and‌​‌ large language models towards​​ more findable and reusable​​​‌ bioinformatics tools.

MLOps best‌ practices for bioinformatics [‌​‌Yann Le Cunff ]​​ 27 Machine learning is​​​‌ increasingly used in bioinformatics‌ for various applications. Developing‌​‌ and maintaining machine learning​​ models requires methods to​​​‌ ensure reproducibility and facilitate‌ the deployment. Unfortunately, these‌​‌ methods are until now​​ rarely used in bioinformatics,​​​‌ and there is a‌ critical need for the‌​‌ adoption of good practices​​ in this field, just​​​‌ as was done in‌ the last years for‌​‌ FAIR management of data,​​ tools or workflows. Machine​​​‌ Learning Operations (MLOps) is‌ a set of practices‌​‌ and tools that offer​​ a very good framework​​​‌ for optimizing machine learning‌ lifecycle management.

8.2 Metabolism:‌​‌ from protein sequences to​​ systems ecology

Participants: Moana​​​‌ Aulagner, Emmanuelle Becker‌, Catherine Belleannée,‌​‌ Samuel Blanquart, Myriam​​ Bontonou, Elisa Chenel​​​‌, François Coste,‌ Pablo Espana Gutierrez,‌​‌ Pauline Giraud, Jeanne​​ Got, Yann Le​​​‌ Cunff, Alice Mataigne‌, Noé Robert,‌​‌ Anne Siegel, Nathalie​​ Théret.

Modeling the​​​‌ emergent metabolic potential of‌ soil microbiomes in Atacama‌​‌ landscapes [Pauline Giraud​​ , Yann Le Cunff​​​‌ , Anne Siegel ]‌ 12 The Atacama Desert’s‌​‌ extreme Talabre Lejía transect​​ serves as a natural​​​‌ lab to study how‌ microbial communities adapt through‌​‌ metabolic interactions. A new​​ computational framework—combining taxonomic/functional profiling,​​​‌ metabolic modeling, and regression—identifies‌ key species and metabolites‌​‌ across six soil samples.​​ Results reveal functional redundancy​​​‌ in metagenomes and site-specific‌ adaptations, linking environmental stressors‌​‌ to microbial survival strategies.​​ The approach is scalable​​​‌ for any (meta)genomic dataset‌ with robust environmental data,‌​‌ offering insights into metabolism-driven​​ resilience in extreme ecosystems.​​​‌

Evolutionary history and association‌ with seaweeds shape the‌​‌ genomes and metabolisms of​​ marine bacteria [Pauline​​​‌ Giraud , Anne Siegel‌ ] 15 Seaweeds support‌​‌ a rich diversity of​​ bacteria, offering metabolic resources​​​‌ and surfaces for biofilm‌ development. To determine whether‌​‌ seaweed-associated bacteria possess unique​​ genetic and metabolic traits​​​‌ compared to their free-living‌ counterparts in seawater, we‌​‌ analyzed genomes from 72​​ bacterial genera across 16​​​‌ different seaweed hosts. The‌ study revealed that taxonomic‌​‌ classification plays a major​​ role in shaping genomic​​​‌ features like GC content,‌ gene number, and genome‌​‌ size. Their genomes reveal​​ metabolic adaptations: enriched pathways​​​‌ for B vitamin synthesis,‌ complex carbohydrate breakdown, and‌​‌ amino acid production—especially in​​ Flavobacteriia. No evidence of​​​‌ host-metabolism complementarity was found‌ in Ectocarpus subulatus and‌​‌ its bacteria. These adaptations​​​‌ may impact coastal carbon,​ nitrogen, and sulfur cycling.​‌

A duo of fungi​​ and complex and dynamic​​​‌ bacterial community networks contribute​ to shape the Ascophyllum​‌ nodosum holobiont [Samuel​​ Blanquart ] 16 The​​​‌ brown alga Ascophyllum nodosum​ and its microbiota form​‌ a dynamic functional entity​​ named holobiont. Some microbial​​​‌ partners may play a​ role in seaweed health​‌ through bioactive compounds crucial​​ for normal morphology, development,​​​‌ and physiological acclimation. However,​ the full spectrum of​‌ the microbial diversity and​​ its variations according to​​​‌ algal life stage, season,​ and location have not​‌ been comprehensively studied. This​​ study uses 208 short-read​​​‌ metabarcoding samples to characterize​ the bacterial, archaeal, and​‌ microeukaryotic communities of A.​​ nodosum across three nearby​​​‌ sites, four thallus parts,​ and a monthly survey,​‌ aiming to explore the​​ dynamics of ecological interactions​​​‌ within the holobiont. Our​ results revealed that A.​‌ nodosum harbors a predominantly​​ bacterial microbiota, varying significantly​​​‌ across all covariables, while​ archaea were virtually absent.​‌ An innovative normalization using​​ the co-amplified host reads​​​‌ provided an estimation of​ bacterial abundance, revealing a​‌ drastic decline in May,​​ potentially linked to epidermal​​​‌ shedding. In contrast, fungal​ communities were stable, dominated​‌ by Mycophycias ascophylli and​​ Moheitospora sp., which​​​‌ remained closely associated with​ the host year-round. We​‌ identified a core microbiome​​ of 22 ASVs, consistently​​​‌ found in all samples,​ including Granulosicoccus, a genus​‌ consistently abundant in other​​ brown algal microbiota. Sequence​​​‌ clustering revealed multiple species​ which vary according to​‌ seasons, even in the​​ overall stable Granulosicoccus genus.​​​‌ Co-occurrence network analysis revealed​ putative interactions between microbial​‌ groups in response to​​ ecological niches. Overall, these​​​‌ findings highlight the dynamic​ of bacterial interactions and​‌ stable fungal associations within​​ the A. nodosum holobiont,​​​‌ providing new insights into​ the ecology of its​‌ microbiota.

Methods for a​​ species-specific genome-scale metabolic model​​​‌ designed for eukaryotes and​ applied to the Ascophyllum​‌ nodosum macroalga [Pauline​​ Giraud , Jeanne Got​​​‌ , Anne Siegel ]​ 19 The Prolipipe pipeline​‌ addresses the challenge of​​ assessing functional variability in​​​‌ food industry-relevant bacteria by​ enabling large-scale metabolic potential​‌ evaluation from genomic data.​​ Leveraging public genome repositories,​​​‌ it automates the construction​ of metabolic networks, with​‌ enzyme identification as a​​ key focus. For hundreds​​​‌ to thousands of bacterial​ genomes, Prolipipe integrates triple-tool​‌ annotation to predict gene​​ functions, builds genome-scale metabolic​​​‌ networks, and maps the​ presence/absence of pathway-specific reactions.​‌ Applied to 1,494 lactic​​ acid bacteria genomes, it​​​‌ evaluated 761 pathways, revealing​ 137 pathways operational in​‌ at least one strain,​​ while four Metacyc functional​​​‌ classes remained unrepresented. The​ pipeline also uncovered infraspecific​‌ variability, highlighting strain-dependent phenotypic​​ differences within species, which​​​‌ underscores the functional diversity​ critical for industrial applications.​‌

Studying metabolic cross-feedings insides​​ phycospheres during cyanobacterial harmful​​​‌ blooms (HCBs) [Jeanne​ Got ] 22 Using​‌ metagenomic, metabolomic and metabolic​​ modelling, we characterised 12​​​‌ Microcystis cyanobacteria and 97​ MAGs from the phycosphere​‌ cultured after isolation from​​ a pond near Paris.​​​‌ Metabolic modelling, identification of​ biosynthetic gene clusters, and​‌ secondary metabolites highlighted differences​​ between the metabolic capacities​​ of the phycosphere and​​​‌ the importance of manual‌ curation of secondary metabolism‌​‌ in metabolic networks. These​​ results deepen our understanding​​​‌ of Microcystis’ phycosphere functioning,‌ demonstrate the relevance of‌​‌ multi-omics systems biology approaches,​​ and lay the fundation​​​‌ for further characterisation of‌ freshwater HCB’s microbial interactions‌​‌ and inter-species complementarity.

Carbon​​ substrates utilization determine antagonistic​​​‌ fungal-fungal interactions among root-associated‌ fungi [Alice Mataigne‌​‌ ] 14 This study​​ explores how fungal metabolism​​​‌ shapes fungal-fungal interactions in‌ the plant microbiome, an‌​‌ area far less understood​​ than bacterial competition. By​​​‌ profiling carbon substrate utilization‌ in 91 root-associated fungal‌​‌ isolates, the authors reveal​​ that fungal carbon usage​​​‌ strategies vary widely—independent of‌ host plant species, root‌​‌ compartment, or geography. Notably,​​ fungi with antifungal-mediated antagonism​​​‌ exhibit broader, faster carbon‌ utilization, while those relying‌​‌ on direct competition use​​ fewer substrates at slower​​​‌ rates. Combined with taxonomy-based‌ enzyme predictions, these findings‌​‌ suggest that carbon utilization​​ profiles and enzymatic reactions​​​‌ could serve as markers‌ of fungal antagonistic potential.‌​‌ Ecologically, this highlights how​​ metabolic diversity among root​​​‌ fungi drives their competitive‌ dynamics, offering new insights‌​‌ into microbiome assembly and​​ fungal interaction networks.

Metagenomic​​​‌ taxonomic assignment using Nanopore‌ reads, reconstruction of metabolic‌​‌ networks and prediction of​​ metabolite production [Jeanne​​​‌ Got , Anne Siegel‌ ] 21 The intestinal‌​‌ microbiota shapes the early-life​​ gut barrier through metabolite​​​‌ production. Using INRAE’s Holopig‌ program, colonic samples from‌​‌ control and colistin-treated piglets​​ were analyzed. The AuCoMe​​​‌ and MeneTools pipelines reconstructed‌ bacterial metabolic networks, revealing‌​‌ strain-level metabolic diversity—shared and​​ unique pathways—within species. Gram-negative​​​‌ bacteria emerged as key‌ producers of metabolites critical‌​‌ for intestinal immunity, permeability,​​ inflammation, and gut-brain signaling.​​​‌ Future work aims to‌ scale this approach for‌​‌ broader microbiota metabolite predictions.​​

FUSE-PhyloTree: Linking functions and​​​‌ sequence conservation modules of‌ a protein family through‌​‌ phylogenomic analysis [Catherine​​ Belleannée , Samuel Blanquart​​​‌ , Elisa Chenel ,‌ François Coste , Nathalie‌​‌ Theret ] 13 FUSE-PhyloTree​​ is a phylogenomic analysis​​​‌ software for identifying local‌ sequence conservation associated with‌​‌ the different functions of​​ a multi-functional (e.g., paralogous​​​‌ or multi-domain) protein family.‌ FUSE-PhyloTree introduces an original‌​‌ approach that combines advanced​​ sequence analysis with phylogenetic​​​‌ methods. First, local sequence‌ conservation modules within the‌​‌ family are identified using​​ partial local multiple sequence​​​‌ alignment. Next, the evolution‌ of the detected modules‌​‌ and known protein functions​​ is inferred within the​​​‌ family's phylogenetic tree using‌ three-level phylogenetic reconciliation and‌​‌ ancestral state reconstruction. As​​ a result, FUSE-PhyloTree provides​​​‌ a gene tree annotated‌ with both predicted sequence‌​‌ modules and ancestral gene​​ functions, enabling the association​​​‌ of functions with specific‌ sequence regions based on‌​‌ their co-emergence. FUSE-PhyloTree is​​ provided as Docker and​​​‌ Singularity images including all‌ the required software tools.‌​‌

8.3 Regulation and signaling:​​ detecting complex and discriminant​​​‌ signatures of phenotypes

Participants:‌ Emmanuelle Becker, Catherine‌​‌ Belleannée, Samuel Blanquart​​, Myriam Bontonou,​​​‌ Olivier Dameron, Juliette‌ Francis, Yann Le‌​‌ Cunff, Corentin Lucas​​, Noryah Safla,​​​‌ Anne Siegel, Nathalie‌ Théret.

Pervasive formation‌​‌ of double-stranded RNAs by​​​‌ overlapping sense/antisense transcripts in​ budding yeast mitosis and​‌ meiosis [Emmanuelle Becker​​ ] 17 Previous RNA​​​‌ profiling studies revealed co-expression​ of overlapping sense/antisense (s/a)​‌ transcripts in pro- and​​ eukaryotic organisms. Functional analyses​​​‌ in yeast have shown​ that certain s/a mRNA/mRNA​‌ and mRNA/lncRNA pairs form​​ stable double-stranded RNAs (dsRNAs)​​​‌ that affect transcript stability.​ Little is known, however,​‌ about the genome-wide prevalence​​ of dsRNA formation and​​​‌ its potential functional implications​ during growth and development​‌ in diploid budding yeast.​​ To address this question,​​​‌ we monitored dsRNAs in​ a Saccharomyces cerevisiae strain​‌ expressing the ribonuclease DCR1​​ and the RNA binding​​​‌ protein AGO1 from Naumovozyma​ castellii. We identify dsRNAs​‌ at 347 s/a loci​​ that express partially or​​​‌ completely overlapping transcripts during​ mitosis, meiosis or both​‌ stages of the diploid​​ life cycle. The data​​​‌ are interesting from an​ evolutionary perspective, since natural​‌ antisense transcripts that form​​ stable dsRNAs have been​​​‌ detected in many species​ from bacteria to humans.​‌ This work was driven​​ by Michaël Primig, collaborator​​​‌ at IRSET (Rennes).

Identifying​ coevolving residues by factoring​‌ out the evolutionary distance​​ covariance matrix [François​​​‌ Coste , Pablo Espana​ Gutierrez ] 26 The​‌ identification of coevolving residues​​ in protein families underlies​​​‌ recent breakthroughs in predicting​ protein structure from sequence,​‌ from early Direct Coupling​​ Analysis (DCA) methods to​​​‌ modern tools like AlphaFold.​ However, as shown by​‌ Qin and Colwell (2018),​​ residue covariations in multiple​​​‌ sequence alignments are heavily​ influenced by phylogenetic relationships.​‌ A key challenge remains:​​ distinguishing covariations due to​​​‌ shared evolutionary history from​ those driven by structural​‌ or functional constraints. Some​​ deep learning architectures, such​​​‌ as MSA Transformers, have​ been introduced to handle​‌ these two sources of​​ signal separately. Here, we​​​‌ investigate a more direct​ approach: explicitly analyzing this​‌ separation within the classical​​ DCA covariance framework. To​​​‌ handle this two-source signal,​ we introduce a novel​‌ method based on a​​ matrix normal law that​​​‌ explicitly separates sequence-level and​ residue-level dependencies via two​‌ covariance matrices instead of​​ one: one for coevolution​​​‌ among residue positions and​ the other for evolutionary​‌ distances between sequences. From​​ this theoretical framework, we​​​‌ derive an estimator of​ the residue-residue covariance matrix​‌ by factoring out the​​ contribution of evolutionary relationships,​​​‌ encoded in the sequence​ distance covariance matrix, from​‌ the observed dependencies. We​​ perform a spectral analysis​​​‌ of this estimator, revealing​ the need for more​‌ refined strategies to estimate​​ the covariance of sequence​​​‌ evolutionary distances. We then​ present two alternative approaches​‌ that better incorporate the​​ phylogenetic history of sequences​​​‌ for improved practical estimation​ of evolutionary distances and​‌ more accurate identification of​​ coevolving residues through their​​​‌ removal in covariance-based Direct​ Coupling Analysis.

9 Bilateral​‌ contracts and grants with​​ industry

9.1 Bilateral Grants​​​‌ with Industry

BeCycle

Participants:​ Jeanne Got, Noé​‌ Robert, Anne Siegel​​.

In the context​​​‌ of the Grand Défi​ "Ferment du futur", this​‌ private-public project aims at​​ scanning thousands of bacterial​​​‌ genomes to identify the​ best consortium of strains​‌ capable of producing metabolites​​ of interest. Duration: 2024-2026,​​ total of the grant​​​‌ 400k€.

10 Partnerships and‌ cooperations

10.1 International initiatives‌​‌

10.1.1 Visits of international​​ scientists

Other international visits​​​‌ to the team
Cathy‌ Pfiser
  • Status
    (researcher, PhD,‌​‌ post-Doc, intern (master/eng))
  • Institution​​ of origin:
    Univ. Chicago​​​‌
  • Country:
    USA
  • Dates:
    December‌ 2025
  • Context of the‌​‌ visit:
    Meeting algometabionte, Rennes,​​ December 2025, 30 participants​​​‌ [Anne Siegel ]‌
  • Mobility program/type of mobility:‌​‌
    research stay
Domenico Palladino​​
  • Status
    PhD student
  • Institution​​​‌ of origin:
    Univ. Salerno‌
  • Country:
    Italy
  • Dates:
    November‌​‌ 2025 - January 2026​​
  • Context of the visit:​​​‌
    Erasmus+ [Olivier Dameron‌ ]
  • Mobility program/type of‌​‌ mobility:
    internship

10.1.2 Visits​​ to international teams

Research​​​‌ stays abroad
Anne Siegel‌
  • Visited institution:
    University of‌​‌ Chile
  • Country:
    Chile
  • Dates:​​
    January 2025
  • Context of​​​‌ the visit:
    Cloture of‌ the associated team biointegrative-chile.‌​‌ Organisation of the workshop​​ metabolic'lub.
  • Mobility program/type of​​​‌ mobility:
    associated team Inria.‌
Anne Siegel
  • Visited institution:‌​‌
    University of Chicago
  • Country:​​
    United States
  • Dates:
    March​​​‌ 2025
  • Context of the‌ visit:
    Visit of the‌​‌ department of environment
  • Mobility​​ program/type of mobility:
    Invitation​​​‌ from the AI Schmidt‌ program.
Anne Siegel
  • Visited‌​‌ institution:
    University of Chile​​
  • Country:
    Chile
  • Dates:
    December​​​‌ 2025
  • Context of the‌ visit:
    Collaboration with CMM‌​‌ and CRG.
  • Mobility program/type​​ of mobility:
    Local invitation​​​‌
Yael Tirlet
  • Visited institution:‌
    Swiss Institute for Bioinformatics‌​‌
  • Country:
    Switzerland
  • Dates:
    May​​ 2025 – July 2025​​​‌
  • Context of the visit:‌
    Starting collaboration
  • Mobility program/type‌​‌ of mobility:
    Doctoral school​​ fellowship

10.2 European initiatives​​​‌

10.2.1 Other european programs/initiatives‌

ERC HoloE2Plant, Exploring the‌​‌ Holobiont concept through a​​ Plant Evolutionary Experiment study​​​‌

Participants: Moana Aulagner,‌ Samuel Blanquart, Anne‌​‌ Siegel.

Exploring the​​ Holobiont concept through a​​​‌ Plant Experimental Evolution study.‌ In her ERC project,‌​‌ Claudia Bartoli aims at​​ validating the holobiont concept,​​​‌ highlighting how the interactions‌ with its microbiota influence‌​‌ a species evolution. The​​ study will apply to​​​‌ a host/pathogen system, Brassica‌ rapa / Rhizoctonia solani,‌​‌ associated with bacterial and​​ fungal synthetic communities. Examining​​​‌ nine plant generations in‌ an experimental-evolution apparatus should‌​‌ reveal the molecular outcomes​​ of the applied selective​​​‌ pressures. 2022-2027, total of‌ the grant 1500k€.

10.3‌​‌ National initiatives

SEABIOZ :​​ Potential microbial origins of​​​‌ the biostimulant properties of‌ extracts from a brown‌​‌ algae holobinte

Participants: Samuel​​ Blanquart, Olivier Dameron​​​‌, Jeanne Got,‌ Anne Siegel.

For‌​‌ sustainable agriculture, new bio-based​​ solutions include biocontrol and​​​‌ the use of plant‌ biostimulants such as aqueous‌​‌ seaweed extracts. The most​​ widely exploited biomass for​​​‌ biostimulant production is the‌ brown seaweed Ascophyllum nodosum‌​‌ and its commercial extracts,​​ including products from the​​​‌ Roullier Group, have demonstrated‌ their ability to improve‌​‌ plant growth and mitigate​​ certain abiotic and biotic​​​‌ stresses. A unique feature‌ of the alga is‌​‌ its mutualistic association with​​ the fungal endophyte Mycophycias​​​‌ ascophylli and other microbes‌ constituting an holobiont. Many‌​‌ questions remain as to​​ the nature and origin​​​‌ of the active compounds‌ in algal extracts. Are‌​‌ these bioactive metabolites produced​​ by the host or​​​‌ by its microbiota? The‌ main objective of SEABIOZ‌​‌ is to answer these​​​‌ questions by combining a​ multi-omics approach and systems​‌ biology. 2021–2025. Dyliss grant:​​ 120k€.

DeepImpact : Deciphering​​​‌ plant-microbiome interactions to enhance​ crop defense to bioagressors​‌

Participants: Samuel Blanquart,​​ Olivier Dameron, Jeanne​​​‌ Got, Alice Mataigne​, Pauline Giraud,​‌ Anne Siegel.

DEEP​​ IMPACT is a multidisciplinary​​​‌ consortium-based project that aims​ at combining ecology, biology,​‌ plant genetics and mathematics​​ to identify, characterize and​​​‌ validate the microbial communities,​ plant communities and abiotic​‌ factors (including agricultural managements)​​ explaining variation in Brassica​​​‌ napus and Triticum aestivum​ resistance to several pests.​‌ For this, we will​​ start from an in​​​‌ situ approach by characterizing​ 100 fields (50 for​‌ each crop species) for​​ both habitat (climatic and​​​‌ edaphic variables) and biotic​ (microbiota, virome, weed communities,​‌ pest attacks and pathobiota​​ prevalence) features. Information from​​​‌ this broad characterization will​ be integrated into sparse​‌ and correlative statistical models​​ to describe the relative​​​‌ part of the variance​ explained by both habitat​‌ and biotic features and​​ correlated with a reduction​​​‌ of pest's attacks. This​ analysis will allow us​‌ to identify a combination​​ of microbial species and​​​‌ soils, correlated with an​ increase of crop's resistance​‌ to pests. These microbial​​ consortia will be isolated​​​‌ by taking advantages of​ newly developed culturomics methods​‌ and characterized by both​​ whole genome sequencing and​​​‌ biochemical assays. Synthetic Consortia​ (SynComs) will be reconstructed​‌ to test their efficacy​​ on a broad range​​​‌ of pests attacking both​ crops. 2021–2026. Dyliss grant:​‌ 176k€.

ENDOVIRE (ANR)

Participants:​​ Emmanuelle Becker, Olivier​​​‌ Dameron, Yael Tirlet​.

The whole ANR​‌ project gathers 4 partners​​ : the BIPAA platform​​​‌ (INRAe), the DGIMI laboratory,​ the BF2I laboratory and​‌ the Dyliss team of​​ IRISA. The project is​​​‌ focused about the understanding​ of how genes of​‌ a endogeneized viral genome​​ in a parasitoid wasp​​​‌ are the activated and​ regulated. The available data​‌ produced by the consortium​​ will cover genomics, epigenomics,​​​‌ pathways, regulation and orthology.​ We will contribute to​‌ identify the key actors​​ involved in the activation​​​‌ of parasitoids genes, to​ propose a data and​‌ knowledge integration framework for​​ the data of the​​​‌ global project, and to​ develop integrative data analysis​‌ methods for elucidating the​​ mechanism involving the key​​​‌ actors identified in the​ first point. It will​‌ consist in proposing a​​ library of queries (which​​​‌ contains a reasoning part),​ and further to propose​‌ regulation mechanisms based on​​ heterogeneous -omics data across​​​‌ interacting organisms. To tackle​ the different challenges, our​‌ appoach will be based​​ on (1) adequate statistical​​​‌ analysis workflows or methods,​ (2) Semantic Web technologies​‌ and AskOmics developed within​​ the team, (3) knowledge-guided​​​‌ traversal strategies across multiplex​ graphs. 2023–2026. Dyliss grant:​‌ 176k€.

PEPR Digital health​​ : ShareFAIR

Participants: Olivier​​​‌ Dameron, Ulysse Le​ Clanche, Yann Le​‌ Cunff.

The increasing​​ availability of life science​​​‌ data offers unprecedented opportunities​ for healthcare research, it​‌ has the potential to​​ revolutionize the way we​​​‌ understand and treat diseases,​ as it allows researchers​‌ to identify trends and​​ patterns that may not​​ have been apparent with​​​‌ smaller data sets. However,‌ exploiting this potential requires‌​‌ innovative solutions for the​​ annotation of biomedical and​​​‌ clinical datasets and extraction‌ of provenance. Challenges thus‌​‌ include standardization and annotation​​ for datasets and protocols,​​​‌ extracting protocols from text‌ and datasets, and synthesizing‌​‌ them into interoperable, yet​​ shareable protocols. ShareFAIR will​​​‌ provide (i) standards to‌ uniformly annotate datasets and‌​‌ protocols with ontologies/common vocabularies​​ and provenance to trace​​​‌ their origin, (ii) an‌ interoperable framework to index,‌​‌ design and annotate reliable​​ and shareable analysis protocols,​​​‌ (iii) approaches to extract‌ new protocols, based on‌​‌ the literature, learned from​​ biomedical and clinical datasets,​​​‌ and from international data‌ challenges in neuroimaging. Dyliss‌​‌ contribution consists in designing​​ a semi-automated dataset FAIRification​​​‌ method that will extend‌ low-level metadata by higher‌​‌ level descriptions inferred from​​ the workflow specification and​​​‌ execution. These descriptions will‌ provide a summary focusing‌​‌ on the “what" rather​​ than the “how", that​​​‌ will be instrumental to‌ workflow recommendation as well‌​‌ as improved reusability of​​ data analysis results. To​​​‌ this end, we will‌ leverage domain-specific knowledge associated‌​‌ to biomedical datasets, as​​ well as fine-grained workflow​​​‌ execution provenance traces so‌ that data analysis results‌​‌ can be more easily​​ understood, explained and shared,​​​‌ in line with critical‌ open and reproducible sciences‌​‌ initiatives. The PhD of​​ Ulysse Le Clanche is​​​‌ co-supervized by Olivier Dameron‌ at Dyliss and Alban‌​‌ Gaignard at Institut du​​ Thorax, INSERM and Univ.​​​‌ Nantes. 2023–2027. Dyliss grant:‌ 185k€.

PEPR Digital agro-ecology‌​‌ : HOLOBIONT

Participants: Juliette​​ Francis, Yann Le​​​‌ Cunff.

Animals and‌ their microbiota form a‌​‌ composite organism, called a​​ holobiont, which can be​​​‌ considered the ultimate unit‌ on which evolution and‌​‌ selection act. Host genes​​ and the environment influence​​​‌ the colonization, development, and‌ function of the various‌​‌ microbiota, which in turn​​ help shape the host's​​​‌ phenotypes. The phenotypes of‌ the holobiont thus result‌​‌ from the combined action​​ of the host genes​​​‌ and those of its‌ microbiota, and their determinism‌​‌ can be explored by​​ implementing hologenetic approaches capable​​​‌ of considering host genomes‌ and metagenomes jointly. The‌​‌ overall objective of this​​ PEPR is to develop​​​‌ integrative hologenetic approaches for‌ animal breeding, using state-of-the-art‌​‌ technologies to generate, process​​ and analyze genetic and​​​‌ genomic datasets of the‌ host and its microbiota‌​‌ as well as the​​ phenotypes and environmental parameters​​​‌ in which the holobionts‌ evolve. To this end,‌​‌ the project aims to​​ develop methods for the​​​‌ analysis of new-generation phenotyping‌ data of the holobiont‌​‌ (mainly high-throughput and continuous),​​ for their modeling and​​​‌ for the analysis of‌ their interrelationships with the‌​‌ microbiota data. Juliette Francis​​ 's Ph.D, co-supervised by​​​‌ Yann Le Cunff (Dyliss)‌ and Mahendra Mariadassou (INRAe,‌​‌ MaIAGe), focuses on co-analyzing​​ genomic data, microbiota data​​​‌ and metabolomic data to‌ efficiently predict a phenotype‌​‌ of interest (food intake​​ efficiency in this case).​​​‌ 2024–2028. Dyliss grant :‌ 178k€.

PEPR Digital health‌​‌ : M4DI

Participants: Emmanuelle​​ Becker, Océane Carpentier​​​‌, Yann Le Cunff‌.

The main objective‌​‌ of the Methods and​​​‌ Models for Multimodal and​ Multiscale Data Integration (M4DI)​‌ project is to develop​​ innovative methodological frameworks for​​​‌ the integration of biomedical​ datasets. In particular, the​‌ team is involved in​​ designing robust machine learning​​​‌ approaches enhanced by prior​ knowledge. In particular, Océane​‌ Carpentier 's Ph.D, co-supervised​​ by Emmanuelle Becker ,​​​‌ Yann Le Cunff (Dyliss),​ Nicolas Jay and Aurélie​‌ Bannay (LORIA, Nancy) is​​ dedicated to exploiting the​​​‌ ontology structure of the​ Gene Ontology database in​‌ machine learning algorithms. One​​ key application will be​​​‌ carried out on a​ local cohort of Crohn's​‌ patients with the CHU​​ of Rennes. 2024–2028. DYLISS​​​‌ grant: 169k€.

CRLnet (ANR)​

Participants: Emmanuelle Becker,​‌ Olivier Dameron.

The​​ whole ANR aims at​​​‌ better understanding the ubiquitin​ system, a vital regulatory​‌ network that controls many​​ different proteins in our​​​‌ cells. It works by​ attaching a small protein​‌ called ubiquitin to other​​ proteins, which either adjusts​​​‌ their activity or marks​ them for degradation. This​‌ system plays a key​​ role in various diseases,​​​‌ including cancer, neurodegenerative disorders,​ and infections. Cullin RING​‌ ligases (CRLs) are crucial​​ components of the ubiquitin​​​‌ system, found in organisms​ ranging from yeast to​‌ humans. They are made​​ up of several interchangeable​​​‌ subunits. Despite two decades​ of research, the different​‌ ways they operate and​​ the cellular proteins they​​​‌ target is still poorly​ understood. The whole ANR​‌ will use budding yeast​​ as a model organism​​​‌ and employ a cutting-edge​ technique called NanoBiT for​‌ identifying CRL interaction partners​​ and create a comprehensive​​​‌ catalog of CRL interaction​ partners. Our contribution to​‌ the ANR aims at​​ priorizing the potential targets​​​‌ identified with the NanoBit​ experiments, by leveraging knowledgebases​‌ about biological interactions (protein-protein​​ interaction, metabolic networks, genetic​​​‌ interactions...). 2025–2029. Dyliss grant:​ 144k€.

10.3.1 Programs funded​‌ by Inria

Exploratory Action​​ ECxit: Exiting the EC​​​‌ Classification for Better Enzyme​ Annotation by Deep Learning​‌

Participants: François Coste.​​

  • Scientific leader: François Coste​​​‌
  • Duration: 2025–2029
  • Description: Deep​ language models, such as​‌ those behind ChatGPT, have​​ revolutionized natural language processing.​​​‌ By treating protein sequences​ as a language, the​‌ ECxit project aims to​​ transfer these advances to​​​‌ the field of biology.​ Its goal is to​‌ develop a novel method​​ and a redesigned classification​​​‌ of enzymes, enabling their​ identification and the precise​‌ prediction of their functions​​ from amino acid sequences,​​​‌ ultimately improving genome annotation.​

11 Dissemination

11.1 Promoting​‌ scientific activities

11.1.1 Scientific​​ events: organisation

Member of​​​‌ the organizing committees
  • Meeting​ algometabionte, Rennes, December 2025,​‌ 30 participants [Anne​​ Siegel ]

11.1.2 Scientific​​​‌ events: selection

Member of​ the conference program committees​‌
  • ISMB-ECCB 2025 (International Symposium​​ on Molecular Biology) [​​​‌Anne Siegel ]
  • Jobim​ 2025 (Journées Ouvertes Biologie​‌ Informatique Mathématiques), France [​​Olivier Dameron ]
  • Journée​​​‌ Santé et IA 2025​ (plateforme IA, Dijon) [​‌Olivier Dameron ]
  • Journées​​ de Biologie In Silico​​​‌ Rennes, France [François​ Coste ]
Reviewer
  • ISMB/ECCB​‌ 2025 [Yann Le​​ Cunff , Emmanuelle Becker​​​‌ ]
  • Jobim 2025 [​Olivier Dameron , Yann​‌ Le Cunff ]
  • Santé​​ et IA 2025 [​​Olivier Dameron ]

11.1.3​​​‌ Journal

Reviewer - reviewing‌ activities
  • Matrix Biology [‌​‌Nathalie Théret ]

11.1.4​​ Invited talks

  • AI Schmidt​​​‌ seminar series, Chicago university,‌ Discovering Functions in Taxonomic‌​‌ Characterization of Environmental Samples:​​ Combining Symbolic Data Science​​​‌ and Machine Learning,‌ Chicago, US, March 2025‌​‌ [Anne Siegel ]​​
  • Metaboliclub, What can we​​​‌ say from taxonomic affiliation‌ : from metabolic functions‌​‌ to classification, Chile,​​ January 2025 [Anne​​​‌ Siegel ]
  • Dynamics in‌ Patagonia, Symbiosis in Environmental‌​‌ Biology, Discretization of Dynamical​​ Systems, Puerto Natales,​​​‌ Chile, Decembre 2025 [‌Anne Siegel ]
  • "Data‌​‌ and knowledge integration, analysis,​​ life cycle and reproducibility​​​‌ in life sciences" INRAe‌ PEPI IBIS, Rennes October‌​‌ 2025 [Olivier Dameron​​ ]
  • Algometabiont days, Rennes​​​‌ December 2025. Beyond EC‌ annotation of enzymes [‌​‌François Coste ]

11.1.5​​ Leadership within the scientific​​​‌ community

National responsibilities
  • Deputy‌ Scientific Directory (CNRS Informatics),‌​‌ in charge of interdisciplinarity​​ between numerical sciences and​​​‌ other disciplines, gender equality‌ in computer sciences, groupements‌​‌ de recherches (GDR), until​​ 01/10/2025 [Anne Siegel​​​‌ ]
  • Scientific officer (CNRS‌ Informatics, gender equality in‌​‌ computer sciences, since 01/10/2025​​ [Anne Siegel ]​​​‌
  • Mediator and Member of‌ the steering committee of‌​‌ the programme LORIER: The​​ Organization for Ethical and​​​‌ Responsible Research at Inserm‌ [Nathalie Théret ]‌​‌
Local responsibilities
  • Scientific Director​​ of the GenOuest platform​​​‌ [Yann Le Cunff‌ ]
  • Responsability of the‌​‌ cross-cutting axis "Health-biology" at​​ IRISA [Yann Le​​​‌ Cunff ]
  • Full member‌ of the Sciences Faculty‌​‌ Counsil at University of​​ Rennes [Emmanuelle Becker​​​‌ ]
  • Head of the‌ Master degree "Bioinformatics" [‌​‌Emmanuelle Becker ]
  • Head​​ of the double-diploma Licence​​​‌ degree "Life Science, Maths‌ and Artificial Intelligence" [‌​‌Yann Le Cunff ]​​
  • Responsability of the 2nd​​​‌ and 3rd years of‌ the "Yes-if" ISTN licence‌​‌ program, Univ. Rennes, France​​ [Catherine Belleannée ]​​​‌
  • In charge of the‌ "Open Day and student‌​‌ fair" for Istic, Univ.​​ Rennes, France [Catherine​​​‌ Belleannée ]
  • Referent teacher,‌ 15h, L1 informatique, Univ.‌​‌ Rennes, France [Catherine​​ Belleannée ]
  • Member of​​​‌ the Parcoursup jury for‌ the Life Science Licence,‌​‌ Univ. Rennes, France [​​Yann Le Cunff ,​​​‌ Emmanuelle Becker ]

11.1.6‌ Scientific expertise

Evaluation of‌​‌ national projects

  • Full member​​ of the Evaluation Committee​​​‌ for ANR section "Interfaces:‌ mathematics, numerical sciences for‌​‌ health and biology" [​​Emmanuelle Becker ]
  • ANRT​​​‌ CIFRE [Olivier Dameron‌ ]

11.1.7 Research administration‌​‌

Institutional boards for the​​ recruitment and evaluation of​​​‌ researchers
  • Professor selection committee‌ University of Rennes (internal‌​‌ promotion, CNU 64) [​​Emmanuelle Becker ]
  • Junior​​​‌ professor selection committee University‌ of Poitiers (CNU 27)‌​‌ [Emmanuelle Becker ]​​
  • Junior professor in Biology​​​‌ and computer sciences selection‌ committee, CNRS [Anne‌​‌ Siegel ]
  • Associate professor​​ selection committee University of​​​‌ Marseille (CNU 26/27)[Emmanuelle‌ Becker ]
  • Associate professor‌​‌ selection committee, Paris City​​ University [Yann Le​​​‌ Cunff ]
  • Non-permanent Associate‌ professor selection committee University‌​‌ of Rennes [Emmanuelle​​ Becker ]
  • Research Engineer​​​‌ selection committee INRAe IGEPP‌ [Emmanuelle Becker ]‌​‌
Scientific councils
  • Scientific referent​​​‌ (for CNRS) of the​ PEPR exploratoire Molecularxiv [​‌Anne Siegel ]
  • Comité​​ de pilotage of the​​​‌ Mission for Interdisciplinarity (MITI)​ at CNRS [Anne​‌ Siegel ]
  • Scientific advisory​​ Board of the LPHI​​​‌ lab [Anne Siegel​ ]
  • Scientific Advisory Board​‌ of the BioGenOuest network​​ (37 platforms) [Emmanuelle​​​‌ Becker ]
  • Scientific Advisory​ Board of the GenOuest​‌ platform [Olivier Dameron​​ ]
Local responsibilities
  • Member​​​‌ of the social committee​ of Univ. Rennes [​‌Catherine Belleannée ]
  • Member​​ of the emergency aid​​​‌ commission of Univ. Rennes​ and Rennes 2 [​‌Catherine Belleannée ]
  • Member​​ of CUMI (Commission des​​​‌ utilisateurs des moyens informatiques)​ of Inria Rennes [​‌François Coste ]
  • Member​​ of the thesis committee​​​‌ of the Matisse doctoral​ school [Olivier Dameron​‌ ]
  • Member of the​​ Inria Rennes center council​​​‌ [Jeanne Got ]​

11.2 Teaching - Supervision​‌ - Juries

11.2.1 Teaching​​

  • Master : Emmanuelle Becker​​​‌ , "R, Data, and​ Visualisation (SIR + PAR​‌ + DVI)", 50h, Master​​ 1 in Bioinformatics, Master​​​‌ 1 in Ecology and​ Environment, Univ. Rennes, France​‌
  • Master : Emmanuelle Becker​​ , "Object oriented programming​​​‌ (OOP)", 60h, Master in​ Bioinformatics, Univ. Rennes, France​‌
  • Licence : Emmanuelle Becker​​ , "Manipulate and Visualize​​​‌ Data (MVD)", 40h, double-diploma​ Licence degree "Life Science,​‌ Maths and Artificial Intelligence"​​ , Univ. Rennes, France​​​‌
  • Master : Emmanuelle Becker​ , "Method (METH)", 15h,​‌ Master 2 in Computer​​ Sciences, Univ. Rennes, France​​​‌
  • Master : Emmanuelle Becker​ , "Manipulate Data with​‌ R (MDR)", 30h, Bioinformatics​​ Minor for Master Students,​​​‌ Univ. Rennes, France
  • Licence​ : Emmanuelle Becker ,​‌ "Biostatistics with R", 12h,​​ L3 Life Science Licence,​​​‌ Univ. Rennes, France
  • Licence:​ Catherine Belleannée , "Formal​‌ Languages", 20h, L3 informatique,​​ Univ. Rennes, France
  • Licence:​​​‌ Catherine Belleannée , "Projet​ professionnel et communication", 16h,​‌ L1 informatique, Univ. Rennes,​​ France
  • Licence: Catherine Belleannée​​​‌ , "Projet professionnel et​ communication", 12h, L2 informatique,​‌ Univ. Rennes, France
  • Licence:​​ Catherine Belleannée , Spécialité​​​‌ informatique, "Functional and immutable​ programming", 44h, L1 mathématiques,​‌ Univ. Rennes, France
  • Master:​​ Catherine Belleannée , "Answer​​​‌ Set Programming", 15h, M1​ informatique, Univ. Rennes, France​‌
  • Master: Catherine Belleannée ,​​ "Programmation logique et contraintes",​​​‌ 32h, M1 informatique, Univ.​ Rennes, France
  • Licence: Catherine​‌ Belleannée , "Outils formels​​ pour l'informatique", 46h, L2​​​‌ informatique, Univ. Rennes, France​
  • Licence: Catherine Belleannée ,​‌ "Fondements mathématiques", 49h, L1​​ informatique, Univ. Rennes, France​​​‌
  • Licence : Myriam Bontonou​ , "Data: Sciences des​‌ Données", 36h, L2 Informatique,​​ ISTIC, Univ. Rennes, France​​​‌
  • Licence : Myriam Bontonou​ , "Programmation Linéaire", 26h,​‌ L3 MIAGE, ISTIC, Univ.​​ Rennes, France
  • Licence :​​​‌ Myriam Bontonou , "GInitiation​ aux sciences informatiques", 6h,​‌ Licence 3 SVT-ME, Faculté​​ des Sciences, Univ. Rennes,​​​‌ France
  • Licence: Olivier Dameron​ , "Programmation 1", 98h,​‌ Licence 1 informatique, Univ.​​ Rennes, France
  • Licence: Olivier​​​‌ Dameron , "Introduction à​ l'IA", 6h, Licence 1​‌ sciences de la vie​​ et de l'environnement, Univ.​​​‌ Rennes, France
  • Licence: Olivier​ Dameron , "Algorithmes de​‌ parcours de données", 25h,​​ Licence 2 sciences de​​​‌ la vie, Univ. Rennes,​ France
  • Licence: Olivier Dameron​‌ , "Graph Modeling and​​ Algorithms", 21h, Licence 2​​ informatique, Univ. Rennes, France​​​‌
  • Licence: Olivier Dameron ,‌ "Programmation avancée", 36h, Licence‌​‌ 3 miage, Univ. Rennes,​​ France
  • Master: Olivier Dameron​​​‌ , "Data Engineering in‌ Life Science", 36h, Master‌​‌ 2 in bioinformatics, Univ.​​ Rennes, France
  • Master: Olivier​​​‌ Dameron , "Internship", 10h,‌ Master 2 in bioinformatics,‌​‌ Univ. Rennes, France
  • Licence:​​ Pablo Espana Gutierrez ,​​​‌ "Langages Formels et Calculabilité",‌ 20h, L3SIF, ENS Rennes,‌​‌ France
  • Licence: Pablo Espana​​ Gutierrez , "Remise à​​​‌ niveau MPI", 10h, L3SIF,‌ ENS Rennes, France
  • Licence:‌​‌ Pablo Espana Gutierrez ,​​ "Préparation à l'agrégation", 5h,​​​‌ ENS Rennes, France
  • Master‌ : Juliette Francis ,‌​‌ "Apprentissage Statistique", 30h, Master​​ 1 in Bioinfortmatics, Univ.​​​‌ Rennes, France
  • Licence :‌ Yann Le Cunff "Modélisation‌​‌ des phénomènes du vivant",​​ 30h, L2 Biologie, Univ.​​​‌ Rennes, France
  • Master: Yann‌ Le Cunff , "Apprentissage‌​‌ statistique", 110h, Master 1​​ in Bioinfortmatics Univ. Rennes,​​​‌ France
  • Master: Yann Le‌ Cunff , "Biologie aux‌​‌ interfaces", 25h, Master 1​​ in Biology, Univ. Rennes,​​​‌ France
  • Master: Yann Le‌ Cunff ,"Simulating dynamic systems‌​‌ in biology", 20h, Master​​ 2 in bioinformatics, Univ.​​​‌ Rennes, France
  • Master: Yann‌ Le Cunff , "Applied‌​‌ Interdisciplinarity", 20h, Master 2​​ in biology, Univ. Rennes,​​​‌ France
  • Master: Yann Le‌ Cunff , "ESG Challenges‌​‌ of Artificial Intelligence", 20h,​​ Master 2 ATN &​​​‌ RSE, Univ. Rennes, France‌
  • Licence : Cécile Beust‌​‌ , "Informatique", 16h, Licence​​ 1 PCSTM, Univ. Rennes,​​​‌ France
  • Licence : Cécile‌ Beust , "Data :‌​‌ Sciences des données", 24h,​​ Licence 2 ISTN, ISTIC,​​​‌ France

11.2.2 Supervision

HDR‌

  • HDR Yann Le Cunff‌​‌ "From Data to Phenotype:​​ Integrating Data Structure and​​​‌ Prior Knowledge to Model‌ Biological Systems" (defended in‌​‌ May 2025)

PhD thesis​​

  • PhD in progress: Moussa​​​‌ Baddour, Extraction de phénotypes‌ à partir de comptes-rendus‌​‌ médicaux textuels et mise​​ en relation avec le​​​‌ génotype, started in May‌ 2023, supervized by Olivier‌​‌ Dameron , M. De​​ Tayrac (Rennes Hospital), S.​​​‌ Paquelet (b<>com) and T.‌ Labbé (Orange)
  • PhD in‌​‌ progress: Yael Tirlet ,​​ Integrative method for multi-omics​​​‌ data analysis with application‌ to the activation and‌​‌ regulation of an endogeneized​​ viral genome in a​​​‌ parasitoid wasp, started in‌ Oct 2023, supervized by‌​‌ Emmanuelle Becker , Olivier​​ Dameron and F. Legeai​​​‌ (INRAe)
  • PhD in progress:‌ Pablo Espana Gutierrez ,‌​‌ Learning models with explicit​​ dependencies between residues to​​​‌ predict protein functions, started‌ in September 2023, supervized‌​‌ by François Coste and​​ Olivier Dameron
  • PhD in​​​‌ progress: Cécile Beust ,‌ Knowledge-guided rules for generating‌​‌ context-specific views on a​​ knowledge graph: application to​​​‌ biological networks, started in‌ Oct 2023, supervized by‌​‌ Emmanuelle Becker , Olivier​​ Dameron and Nathalie Théret​​​‌
  • PhD in progress: Corentin‌ Lucas , Integration of‌​‌ multi-modal data for longitudinal​​ follow-up of Crohn's disease​​​‌ patients, started in Oct‌ 2023, supervized by Emmanuelle‌​‌ Becker , Yann Le​​ Cunff
  • PhD in progress:​​​‌ Moana Aulagner , Modeling‌ microbiota interactions in plants‌​‌ to build synthetic microbial​​ communities for enhanced biocontrol​​​‌ and biostimulation, started in‌ Oct 2023, supervized by‌​‌ Samuel Blanquart , Anne​​ Siegel and C. Bartoli-Kautski​​​‌ (INRAe)
  • PhD in progress:‌ Océane Carpentier , Integrating‌​‌ prior knowledge for a​​​‌ better patient representation, started​ September 2024, supervized by​‌ Emmanuelle Becker , Yann​​ Le Cunff , A.​​​‌ Bannay and N. Jay​ (LORIA)
  • PhD in progress:​‌ Elisa Chenel , Study​​ of protein co-evolution to​​​‌ identify interaction regions involved​ in TGFbeta growth factor​‌ activation, started in Oct​​ 2024, supervized by Samuel​​​‌ Blanquart , François Coste​ and N. Nathalie Théret​‌
  • PhD in progress: Juliette​​ Francis , Integration of​​​‌ heterogeneous data for phenotype​ prediction, started in October​‌ 2024, supervized by Yann​​ Le Cunff and M.​​​‌ Mariadasssou (INRAe)
  • PhD in​ progress: Ulysse Le Clanche​‌ , Knowledge-driven dataset FAIRification:​​ from workflow runs to​​​‌ domain-specific annotations, started in​ October 2024, supervized by​‌ Olivier Dameron and A.​​ Gaignard (CNRS, Institut du​​​‌ Thorax INSERM Nantes)
  • PhD​ in progress: Pauline Giraud​‌ , Hybrid methods for​​ ab initio inference of​​​‌ metabolic pathways in marine​ eukaryotes, started in November​‌ 2024, supervized by Anne​​ Siegel and G. Markov​​​‌ (CNRS, Station biologique de​ Roscoff)
  • PhD in progress:​‌ Noé Robert , Data​​ mining for high-throughput genome​​​‌ screening: predicting microbial synthesis​ capabilities of targeted metabolites,​‌ started in November 2025,​​ supervized by Anne Siegel​​​‌ and Hélène Falentin (INRAE).​
  • PhD in progress: Noryah​‌ Safla , Integration of​​ a priori knowledge into​​​‌ spatial transcriptomics models: application​ to the characterization of​‌ immune response and prediction​​ of treatment resistance in​​​‌ cholangiocarcinoma, started in November​ 2025, supervized by Yann​‌ Le Cunff , Myriam​​ Bontonou and Joachim Lupberger​​​‌ (INSERM)

Internship

  • M2 internship:​ Noryah Safla , Bioinformatic​‌ analysis of mechanisms of​​ resistance to immunotherapy in​​​‌ liver cancer. Jan-Jul 2025​ supervized by Yann Le​‌ Cunff and Myriam Bontonou​​ .
  • M1 internship Daniel​​​‌ Calvez Interprétation des fonctions​ enzymatiques inférées à partir​‌ de données de microbiotes.​​ April - July 2025,​​​‌ supervized by Anne Siegel​ and Myriam Bontonou .​‌
  • M1 internship Samuel Fosse​​ Raisonnement sur des métadonnées​​​‌ issues de génomes. October​ 2025 - May 2026,​‌ supervized by Anne Siegel​​

11.2.3 Doctoral advisory committees​​​‌ (CSID)

  • Rim Ait Ben​ Aoumar, Univ. Rennes [​‌Yann Le Cunff ]​​
  • Maria-Mafalda Almeida, Univ. Rennes​​​‌ [Emmanuelle Becker ]​
  • Alexandre Asset, AgroParisTech [​‌Yann Le Cunff ]​​
  • Juan Andrés Cisneros–Jacome, Univ.​​​‌ Rennes [Emmanuelle Becker​ ]
  • Maëlys Auffret, Univ.​‌ Rennes 2 [Emmanuelle​​ Becker ]
  • Dorian Chenet,​​​‌ Univ. Rennes [Samuel​ Blanquart ]
  • Guénolé Dande,​‌ Univ. de Rennes [​​Olivier Dameron ]
  • Guillaume​​​‌ Doré, Univ. Rennes [​Emmanuelle Becker ]
  • Jin-Mei​‌ Gao, Université Paris-Saclay [​​Emmanuelle Becker ]
  • Zainab​​​‌ Ghrayeb, Univ. de Rennes​ [Olivier Dameron ]​‌
  • Silvia Grosso, INSA Lyon​​ [Yann Le Cunff​​​‌ ]
  • Jedrej Kubica, Univ.​ Grenoble-Alpes [Yann Le​‌ Cunff ]
  • Mats Kohler–Dijkstra,​​ Univ. Rennes [Emmanuelle​​​‌ Becker ]
  • Adam Lakdhari,​ Univ Rennes [Anne​‌ Siegel ]
  • Gabriel Mastrilli,​​ Univ. de Rennes [​​​‌François Coste ]
  • Meije​ Mathé, Univ. Toulouse [​‌Olivier Dameron ]
  • Thiviya​​ Parthipan, Univ. Rennes [​​​‌Samuel Blanquart ]
  • Quentin​ Rouger, Univ. Rennes [​‌Emmanuelle Becker ]
  • Quentin​​ Vacher, Univ. Rennes [​​​‌Emmanuelle Becker ]
  • Maelle​ Zonnequin, Sorbonne Université [​‌Anne Siegel ]

11.2.4​​ Juries

Referee of PhD​​ thesis

  • Sofiane Bouirdene, Univ.​​​‌ Laval Canada [Emmanuelle‌ Becker ]
  • Samuel Dussault,‌​‌ Univ. Sherbrooke Canada [​​Olivier Dameron ]
  • Danilo​​​‌ Dursoniah, Univ. Lille [‌Anne Siegel ]
  • Ludivine‌​‌ Vasseur, Univ. Lille [​​Nathalie Théret ]
  • Catalina​​​‌ Gomez-Gonzalez, Univ. Lyon [‌Emmanuelle Becker ]
  • Yanis‌​‌ Asloudj, Univ. Bordeaux [​​Emmanuelle Becker ]
  • Rola​​​‌ Shaaban, Univ. Nantes [‌Emmanuelle Becker ]

Member‌​‌ of PhD thesis juries​​

  • Maelle Zonnequin, Univ. Paris​​​‌ Sorbonne [Anne Siegel‌ ]
  • Matheo Lode, Univ.‌​‌ Rennes [Nathalie Théret​​ , president]
  • Fabien Foucher,​​​‌ Univ. Rennes [Nathalie‌ Théret , president]
  • Dzenis‌​‌ Koca, Univ. Grenoble Alpes​​ [Emmanuelle Becker ,​​​‌ president]

Member of habilitation‌ thesis juries

  • Clémence Frioux,‌​‌ Univ. Bordeaux [Emmanuelle​​ Becker , referee]
  • Yann​​​‌ Le Cunff, Univ. Rennes‌ [Emmanuelle Becker ]‌​‌

11.3 Popularization

11.3.1 Participation​​ in Live events

  • Intervention​​​‌ and supervision of research‌ workshops at "Réunions des‌​‌ Jeunes Mathématiciennes et Informaticiennes"​​ (RJMI) organized by Animath​​​‌ and Femmes & mathématiques‌ at ENS Rennes [‌​‌Pablo Espana Gutierrez ].​​
  • Scientific outreach intervention for​​​‌ middle-school students as part‌ of the “Parcours Avenir”‌​‌ programme, meeting with women​​ scientists, Collège François Truffaut,​​​‌ Betton [Elisa Chenel‌ ]

12 Scientific production‌​‌

12.1 Major publications

  • 1​​ articleM.Méziane Aite​​​‌, M.Marie Chevallier‌, C.Clémence Frioux‌​‌, C.Camille Trottier​​, J.Jeanne Got​​​‌, M.-P.Maria-Paz Cortés‌, S. N.Sebastian‌​‌ N. Mendoza, G.​​Grégory Carrier, O.​​​‌Olivier Dameron, N.‌Nicolas Guillaudeux, M.‌​‌Mauricio Latorre, N.​​Nicolas Loira, G.​​​‌ V.Gabriel V. Markov‌, A.Alejandro Maass‌​‌ and A.Anne Siegel​​. Traceability, reproducibility and​​​‌ wiki-exploration for "à-la-carte" reconstructions‌ of genome-scale metabolic models‌​‌.PLoS Computational Biology​​145e1006146May​​​‌ 2018HALDOIback‌ to text
  • 2 inproceedings‌​‌C.Catherine Belleannée,​​ O.Olivier Sallou and​​​‌ J.Jacques Nicolas.‌ Logol: Expressive Pattern Matching‌​‌ in sequences. Application to​​ Ribosomal Frameshift Modeling.​​​‌PRIB2014 - Pattern Recognition‌ in Bioinformatics, 9th IAPR‌​‌ International Conference8626Lukas​​ KALLStockholm, SwedenSpringer​​​‌ International PublishingAugust 2014‌, 34-47HALDOI‌​‌back to text
  • 3​​ articleC.Charles Bettembourg​​​‌, C.Christian Diot‌ and O.Olivier Dameron‌​‌. Optimal Threshold Determination​​ for Interpreting Semantic Similarity​​​‌ and Particularity: Application to‌ the Comparison of Gene‌​‌ Sets and Metabolic Pathways​​ Using GO and ChEBI​​​‌.PLoS ONE2015‌, 30HALDOI‌​‌
  • 4 articleP.Philippe​​ Bordron, M.Mauricio​​​‌ Latorre, M.-P.Maria-Paz‌ Cortés, M.Mauricio‌​‌ Gonzales, S.Sven​​ Thiele, A.Anne​​​‌ Siegel, A.Alejandro‌ Maass and D.Damien‌​‌ Eveillard. Putative bacterial​​ interactions from metagenomic knowledge​​​‌ with an integrative systems‌ ecology approach.MicrobiologyOpen‌​‌512015,​​ 106-117HALDOIback​​​‌ to text
  • 5 inproceedings‌J.Jean Coquet,‌​‌ N.Nathalie Théret,​​ V.Vincent Legagneux and​​​‌ O.Olivier Dameron.‌ Identifying Functional Families of‌​‌ Trajectories in Biological Pathways​​ by Soft Clustering: Application​​​‌ to TGF- Signaling.‌CMSB 2017 - 15th‌​‌ International Conference on Computational​​​‌ Methods in Systems Biology​Lecture Notes in Computer​‌ SciencesDarmstadtSeptember 2017​​, 17HALback​​​‌ to text
  • 6 inproceedings​F.François Coste,​‌ G.Gaëlle Garet,​​ A.Agnès Groisillier,​​​‌ J.Jacques Nicolas and​ T.Thierry Tonon.​‌ Automated Enzyme classification by​​ Formal Concept Analysis.​​​‌ICFCA - 12th International​ Conference on Formal Concept​‌ AnalysisCluj-Napoca, RomaniaSpringer​​June 2014HALback​​​‌ to text
  • 7 inproceedings​F.François Coste and​‌ J.Jacques Nicolas.​​ Learning local substitutable context-free​​​‌ languages from positive examples​ in polynomial time and​‌ data by reduction.​​ICGI 2018 - 14th​​​‌ International Conference on Grammatical​ Inference93Wrocław, Poland​‌September 2018, 155​​ - 168HAL
  • 8​​​‌ articleC.Clémence Frioux​, E.Enora Fremy​‌, C.Camille Trottier​​ and A.Anne Siegel​​​‌. Scalable and exhaustive​ screening of metabolic functions​‌ carried out by microbial​​ consortia.Bioinformatics34​​​‌17September 2018,​ i934 - i943HAL​‌DOI
  • 9 articleC.​​Clémence Frioux, T.​​​‌Torsten Schaub, S.​Sebastian Schellhorn, A.​‌Anne Siegel and P.​​Philipp Wanko. Hybrid​​​‌ Metitebolic Network Completion.​Theory and Practice of​‌ Logic ProgrammingNovember 2018​​, 1-23HALback​​​‌ to text
  • 10 article​S.Sylvain Prigent,​‌ C.Clémence Frioux,​​ S. M.Simon M​​​‌ Dittami, S.Sven​ Thiele, A.Abdelhalim​‌ Larhlimi, G.Guillaume​​ Collet, G.Gutknecht​​​‌ Fabien, J.Jeanne​ Got, D.Damien​‌ Eveillard, J.Jérémie​​ Bourdon, F.Frédéric​​​‌ Plewniak, T.Thierry​ Tonon and A.Anne​‌ Siegel. Meneco, a​​ Topology-Based Gap-Filling Tool Applicable​​​‌ to Degraded Genome-Wide Metabolic​ Networks.PLoS Computational​‌ Biology131January​​ 2017, 32HAL​​​‌DOIback to text​
  • 11 articleS.Santiago​‌ Videla, J.Julio​​ Saez-Rodriguez, C.Carito​​​‌ Guziolowski and A.Anne​ Siegel. caspo: a​‌ toolbox for automated reasoning​​ on the response of​​​‌ logical signaling networks families​.Bioinformatics2017HAL​‌DOIback to text​​back to text

12.2​​​‌ Publications of the year​

International journals

International‌​‌ peer-reviewed conferences

National peer-reviewed​​​‌ Conferences

Conferences without proceedings‌​‌

Reports​​ & preprints

Other​ scientific publications

Software

12.3 Cited publications

  • 29​​​‌ articleG.Geoffroy Andrieux​, M.Michel Le​‌ Borgne and N.Nathalie​​ Théret. An integrative​​​‌ modeling framework reveals plasticity​ of TGF-Beta signaling.​‌BMC Systems Biology8​​12014, 30​​​‌HALDOIback to​ textback to text​‌back to text
  • 30​​ articleA.Arnaud Belcour​​, C.Clémence Frioux​​​‌, M.Méziane Aite‌, A.Anthony Bretaudeau‌​‌, F.Falk Hildebrand​​ and A.Anne Siegel​​​‌. Metage2Metabo, microbiota-scale metabolic‌ complementarity for the identification‌​‌ of key species.​​eLife9December 2020​​​‌HALDOIback to‌ text
  • 31 articleA.‌​‌Arnaud Belcour, J.​​Jean Girard, M.​​​‌Méziane Aite, L.‌Ludovic Delage, C.‌​‌Camille Trottier, C.​​Charlotte Marteau, C.-J.​​​‌ J.Cédric J-J Leroux‌, S. M.Simon‌​‌ M. Dittami, P.​​Pierre Sauleau, E.​​​‌Erwan Corre, J.‌Jacques Nicolas, C.‌​‌Catherine Boyen, C.​​Catherine Leblanc, J.​​​‌Jonas Collén, A.‌Anne Siegel and G.‌​‌ V.Gabriel V Markov​​. Inferring Biochemical Reactions​​​‌ and Metabolite Structures to‌ Understand Metabolic Pathway Drift‌​‌.iScience232​​February 2020, 100849​​​‌HALDOIback to‌ text
  • 32 articleA.‌​‌Arnaud Belcour, J.​​Jeanne Got, M.​​​‌Méziane Aite, L.‌Ludovic Delage, J.‌​‌Jonas Collén, C.​​Clémence Frioux, C.​​​‌Catherine Leblanc, S.‌ M.Simon M Dittami‌​‌, S.Samuel Blanquart​​, G. V.Gabriel​​​‌ V. Markov and A.‌Anne Siegel. Inferring‌​‌ and comparing metabolism across​​ heterogeneous sets of annotated​​​‌ genomes using AuCoMe.‌Genome Research33June‌​‌ 2023, 972 -​​ 987HALDOIback​​​‌ to text
  • 33 article‌T.Tim Berners Lee‌​‌, W.Wendy Hall​​, J. A.James​​​‌ A. Hendler, K.‌Kieron O'Hara, N.‌​‌Nigel Shadbolt and D.​​ J.Daniel J. Weitzner​​​‌. A Framework for‌ Web Science.Foundations‌​‌ and Trends in Web​​ Science112007​​​‌, 1--130back to‌ text
  • 34 articleC.‌​‌Charles Bettembourg, C.​​Christian Diot and O.​​​‌Olivier Dameron. Semantic‌ particularity measure for functional‌​‌ characterization of gene sets​​ using gene ontology.​​​‌PLoS ONE91‌e865252014HALDOI‌​‌back to text
  • 35​​ articleS.Samuel Blanquart​​​‌, J.-S.Jean-Stéphane Varré‌, P.Paul Guertin‌​‌, A.Amandine Perrin​​, A.Anne Bergeron​​​‌ and K. M.Krister‌ M. Swenson. Assisted‌​‌ transcriptome reconstruction and splicing​​ orthology.BMC Genomics​​​‌1710Nov 2016‌, 786URL: https://doi.org/10.1186/s12864-016-3103-6‌​‌DOIback to text​​
  • 36 articleP.Pierre​​​‌ Blavy, F.Florence‌ Gondret, S.Sandrine‌​‌ Lagarrigue, J.Jaap​​ Van Milgen and A.​​​‌Anne Siegel. Using‌ a large-scale knowledge database‌​‌ on reactions and regulations​​ to propose key upstream​​​‌ regulators of various sets‌ of molecules participating in‌​‌ cell metabolism.BMC​​ Systems Biology81​​​‌2014, 32HAL‌DOIback to text‌​‌back to text
  • 37​​ articleP.Philippe Bordron​​​‌, M.Mauricio Latorre‌, M.-P.Maria-Paz Cortés‌​‌, M.Mauricio Gonzales​​, S.Sven Thiele​​​‌, A.Anne Siegel‌, A.Alejandro Maass‌​‌ and D.Damien Eveillard​​. Putative bacterial interactions​​​‌ from metagenomic knowledge with‌ an integrative systems ecology‌​‌ approach.MicrobiologyOpen5​​12015, 106-117​​​‌HALDOIback to‌ text
  • 38 incollectionM.‌​‌Matthieu Bouguéon, P.​​​‌Pierre Boutillier, J.​Jérôme Feret, O.​‌Octave Hazard and N.​​Nathalie Théret. The​​​‌ rule-based model approach. A​ Kappa model for hepatic​‌ stellate cells activation by​​ TGFB1.Systems Biology​​​‌ Modelling and Analysis: Formal​ Bioinformatics Methods and Tools​‌WileyNovember 2022,​​ 1-76HALback to​​​‌ text
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