Fey, Dirk[Université de Liège - ULg > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation : Méth. computat. pour la bio.syst. >]
University of Liege
[en] systems biology ; dynamic modelling ; parameter estimation ; nonlinear observers ; learning and memory ; semidefinite programming
[en] This thesis concerns the identification of dynamic models in systems biology. and is structured into two parts. Both parts concern building dynamic models from observed data, but are quite different in perspective, rationale and mathematics. The first part considers the development of novel identification techniques that are particularly tailored to (molecular) biology and considers two approaches. The first approach reformulates the parameter estimation problem as a feasibility problem. This reformulation allows the invalidation of models by analysing entire parameter regions. The second approach utilises nonlinear observers and a transformation of the model equations into parameter free coordinates. The parameter free coordinates allow the design of a globally convergent observer, which in turn estimates the parameter values, and further, allows to identify modelling errors or unknown inputs/influences. Both approaches are bottom up approaches that require a mechanistic understanding of the underlying processes (in terms of a biochemical reaction network) leading to complex nonlinear models. The second part is an example of what can be done with classical, well developed tools from systems identification when applied to hitherto unattended problems.In particular, part two of my thesis develops a modelling framework for rat movements in an experimental setup that it widely used to study learning and memory.The approach is a top down approach that is data driven resulting in simple linear models.