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Dynamique d'un réseau métabolique avec un modèle à base de contraintes : approche par échantillonnage des trajectoires solutions

Abstract : In this thesis, I propose an approach based on the formalism of constraint-based models to study the dynamics of a metabolic system. By combining the sampling of the solutions space and the use of a "feasibility" constraint between the considered time periods, this approach allows to model the dynamic of a metabolic system taking into account the variability of experimental measurements. The feasibility constraint between time periods ensures that each "solution trajectory" corresponds to a succession of flux maps which leads to some kinetics of concentrations that are consistent with the experimental measurements. The generation of a population of solution trajectories allows several analyses. On the one hand, the predicted flux maps can be used to estimate the most plausible flux within the network studied. On the other hand, the distribution of predicted concentrations enables to assess the model used for studying the metabolic network. The fact that this approach is based on the formalism of constraint-based modeling allows, using the steady-state assumption of the system, to study metabolic networks of relatively large size, and to use experimental data that are easily measurable, such as biomass concentration and extracellular metabolites concentration. This approach by "solution trajectories" has been used to study the dynamics of the metabolism of Corynebacterium glutamicum, when grown under biotin-limited condition. The results allowed, first, to attest the functioning of the method, and second, to propose several hypotheses about biological phenomena that take place during this particular growth condition.
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Thomas Duigou. Dynamique d'un réseau métabolique avec un modèle à base de contraintes : approche par échantillonnage des trajectoires solutions. Bio-Informatique, Biologie Systémique [q-bio.QM]. Université Paris Sud - Paris XI, 2015. Français. ⟨NNT : 2015PA112061⟩. ⟨tel-01674162⟩

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