Robustness analysis of biochemical network models

Kim, Jongrae, Bates, Declan, Postlethwaite, Ian, Ma, Lan and Iglesias, Pablo A. (2006) Robustness analysis of biochemical network models. IEE Proceedings - Systems Biology, 153 (3). pp. 96-104. ISSN 1741-2471

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Abstract

Biological systems that have been experimentally verified to be robust to significant changes in their environments require mathematical models that are themselves robust. In this context, a necessary condition for model robustness is that the model dynamics should not be sensitive to small variations in the model's parameters. Robustness analysis problems of this type have been extensively studied in the field of robust control theory and have been found to be very difficult to solve in general. The authors describe how some tools from robust control theory and nonlinear optimisation can be used to analyse the robustness of a recently proposed model of the molecular network underlying adenosine 3',5'-cyclic monophosphate (cAMP) oscillations observed in fields of chemotactic Dictyostelium cells. The network model, which consists of a system of seven coupled nonlinear differential equations, accurately reproduces the spontaneous oscillations in cAMP observed during the early development of D. discoideum. The analysis by the authors reveals, however, that very small variations in the model parameters can effectively destroy the required oscillatory dynamics. A biological interpretation of the analysis results is that correct functioning of a particular positive feedback loop in the proposed model is crucial to maintaining the required oscillatory dynamics.

Item Type:	Article
Uncontrolled Keywords:	oscillations, cellular biophysics, molecular biophysics, robust control, biochemistry, physiological models, nonlinear differential equations, feedback, optimisation
Subjects:	C700 Molecular Biology, Biophysics and Biochemistry H600 Electronic and Electrical Engineering
Department:	Faculties > Engineering and Environment > Mathematics, Physics and Electrical Engineering
Depositing User:	Sarah Howells
Date Deposited:	11 Dec 2012 10:19
Last Modified:	13 Oct 2019 00:23
URI:	http://nrl.northumbria.ac.uk/id/eprint/10763

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