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dc.contributor.advisorSherman, David James
dc.contributor.authorASSAR CUEVAS, Rodrigo
dc.contributor.otherGriffault, Alain
dc.date2011
dc.date.accessioned2020
dc.date.accessioned2020
dc.date.available2020
dc.date.available2020
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/21045
dc.identifier.nnt2011BOR14335
dc.description.abstractLes fonctions biologiques sont le résultat de l'interaction de beaucoup de processus, avec différents objectifs, complexités, niveaux de hiérarchie, et changements de conditions que modifient le comportement de systèmes. Nous utilisons des équations différentielles ou dynamiques plus générales, et systèmes stochastiques de transition pour décrire la dynamique de changements des modèles. La composition, réconciliation et réutilisation des modèles nous permettent d'obtenir des descriptions de systèmes biologiques complètes et compatibles et leur combiner. Notre spécification de systèmes hybrides avec BioRica assure l'intégrité de modèles, et implémente notre approche. Nous appliquons notre approche pour décrire in-silico deux systèmes: la dynamique de la fermentation du vin, et des décisions cellulaires associées à la formation de tissu d'os.
dc.description.abstractEnThe main aim of this thesis is to develop an approach that allows us to describe biological systems with theoretical sustenance and good results in practice. Biological functions are the result of the interaction of many processes, that connect different hierarchy levels going from macroscopic to microscopic level. Each process works in different way, with its own goal, complexity and hierarchy level. In addition, it is common to observe that changes in the conditions, such as nutrients or environment, modify the behavior of the systems. So, to describe the behavior of a biological system over time, it is convenient to combine different types of models: continuous models for gradual changes, discrete models for instantaneous changes, deterministic models for completely predictable behaviors, and stochastic or non- deterministic models to describe behaviors with imprecise or incomplete information. In this thesis we use the theory of Composition and Hybrid Systems as basis, and the BioRica framework as tool to model biological systems and analyze their emergent properties in silico.With respect to Hybrid Systems, we considered continuous models given by sets of differential equations or more general dynamics. We used Stochastic Transition Systems to describe the dynamics of model changes, allowing cofficient switches that control the parameters of the continuous model, and strong switches that choose different models. Composition, reconciliation and reusing of models allow us to build complete and consistent descriptions of complex biological systems by combining them. Compositions of hybrid systems are hybrid systems, and the refinement of a model forming part of a composed system results in a refinement of the composed system. To implement our approach ideas we complemented the theory of our approach with the improving of the BioRica framework. We contributed to do that giving a BioRica specification of Hybrid Systems that assures integrity of models, allowing composition, reconciliation, and reuse of models with SBML specification.We applied our approach to describe two systems: wine fermentation kinetics, and cell fate decisions leading to bone and fat formation. In the case of wine fermentation, we reused known models that describe the responses of yeasts cells to different temperatures, quantities of resources and toxins, and we reconciled these models choosing the model with best adjustment to experimental data depending on the initial conditions and fermentation variable. The resulting model can be applied to avoid process problems as stuck and sluggish fermentations. With respect to cell fate decisions the idea is very ambitious. By using accurate models to predict the bone and fat formation in response to activation of pathways such as the Wnt pathway, and changes of conditions affecting these functions such as increments in Homocysteine, one can analyze the responses to treatments for osteoporosis and other bone mass disorders. We think that here we are giving a first step to obtain in silico evaluations of medical treatments before testing them in vitro or in vivo.
dc.language.isoen
dc.subjectSystèmes biologiques
dc.subjectSystèmes hybrides
dc.subjectComposition
dc.subjectRéconciliation et reutilisation des modèles
dc.subjectBioRica
dc.subjectDynamique de la fermentation du vin
dc.subjectFormation de tissu d'os
dc.subject.enBiological systems
dc.subject.enHybrid systems
dc.subject.enComposition
dc.subject.enReusing and reconciling models
dc.subject.enBioRica
dc.subject.enWine fermentation kinetics
dc.subject.enBone formation
dc.title.enModeling and simulation of hybrid systems and cell factory applications
dc.typeThèses de doctorat
bordeaux.hal.laboratoriesThèses de l'Université de Bordeaux avant 2014*
bordeaux.hal.laboratoriesThèses de l'université de Bordeaux 1
bordeaux.hal.laboratoriesLaboratoire bordelais de recherche en informatique
bordeaux.institutionBordeaux INP
bordeaux.institutionUniversité de Bordeaux
bordeaux.type.institutionBordeaux 1
bordeaux.thesis.disciplineInformatique
bordeaux.ecole.doctoraleÉcole doctorale de mathématiques et informatique (Talence, Gironde)
star.origin.linkhttps://www.theses.fr/2011BOR14335
dc.contributor.rapporteurCouvreur, Jean-Michel
dc.contributor.rapporteurMartínez, Servet
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=ASSAR%20CUEVAS,%20Rodrigo&rft.genre=unknown


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