Investigating host-microbiota cooperation with gap-filling optimization problems

Abstract : Systems biology relies on computational biology to integrate knowledge and data, for a better understanding of organisms’ physiology. Challenges reside in the applicability of methods and tools to non-model organisms, for instance in marine biology. Sequencing advances and the growing importance of elucidating microbiotas’ roles, have led to an increased interest into these organisms. This thesis focuses on the modeling of the metabolism through networks, and of its functionality using graphs and constraints semantics. In particular, a first part presents work on gap-filling metabolic networks in the context of non-model organisms. A graph-based method is benchmarked and validated and a hybrid one is developed using Answer Set Programming (ASP) and linear programming. Such gap-filling is applied on algae and extended to decipher putative interactions between Ectocarpus siliculosus and a symbiotic bacterium. In this direction, the second part of the thesis aims at proposing formalisms and implementation of a tool for selecting and screening communities of interest within microbiotas. It enables to scale to large microbiotas and, with a two-step approach, to suggest symbionts that fit the desired objective. The modeling supports the computation of exchanges, and solving can cover the whole solution space. Applications are presented on the human gut microbiota and the selection of bacterial communities for a brown alga. Altogether, this thesis proposes modeling, software and biological applications using graph-based semantics to support the elaboration of hypotheses for elucidating the metabolism of organisms.
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Clémence Frioux. Investigating host-microbiota cooperation with gap-filling optimization problems. Bioinformatics [q-bio.QM]. Université Rennes 1, 2018. English. ⟨NNT : 2018REN1S058⟩. ⟨tel-01945853v2⟩

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