Modèles qualitatifs de réseaux génétiques : réduction de modèles et introduction d'un temps continu

Abstract : Formal methods from computer science constitute a powerful tool for the modelling of gene networks, including the study of their dynamics. The discrete modelling of René Thomas allows for a proper representation of biological knowledge as well as for use of formal methods. These models have two main limitations: the underlying combinatorics does not allow one to process very large networks, and the chronometric aspects are not taken into account. This thesis offers two contributions according to these issues. The design of gene network models begins with a selectiCalibrion of the most relevant entities. The resulting networks are often too large, and we show how to reduce them without altering the important dynamic properties. Here, we define a completely formal framework, inspired by a technique from Aurélien Naldi, driving the suppression of variables or thresholds. These reductions preserve the asymptotic behaviour. We formally prove the asymptotic equivalence of different published models for the same network. In order to take into account chronometric information that are crucial in some systems (e.g. circadian cycle), we define a hybrid formalism based on the Thomas' formalism where expression levels are discrete but time is continuous. This framework allows for the construction of an abstract model of the circadian clock in mammals. The model explains with very few variables the robustness of the system when submitted to duration changes of the day/night alternation.
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Emilien Cornillon. Modèles qualitatifs de réseaux génétiques : réduction de modèles et introduction d'un temps continu. Autre [cs.OH]. Université Côte d'Azur, 2017. Français. ⟨NNT : 2017AZUR4085⟩. ⟨tel-01682212⟩

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