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Parameter identifiability of biochemical reaction networks in systems biology

Geffen, Dara
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado Formato: 1324816 bytes; application/pdf
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In systems biology, models often contain a large number of unknown or only roughly known parameters that must be estimated through the fitting of data. This work examines the question of whether or not these parameters can in fact be estimated from available measurements. Structural or a priori identifiability of unknown parameters in biochemical reaction networks is considered. Such systems consist of continuous time, nonlinear differential equations. Several methods for analyzing identifiability of such systems exist, most of which restate the question as one of observability by expanding the state space to include parameters. However, these existing methods were not developed with biological systems in mind, so do not necessarily address the specific challenges posed by this type of problem. In this work, such methods are considered for the analysis of a representative biological system, the NF-kappaB signal transduction pathway. It is shown that existing observability-based strategies, which rely on finding an analytical solution, require significant simplifications to be applicable to systems biology problems that are seldom feasible. The analytical nature of the solution imposes restrictions on the size and complexity of systems that these methods can handle. This conflicts with the fact that most currently studied systems biology models are rather large networks containing many states and parameters. In this thesis...