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Inverse Problems in Systems Biology

Heinz W Engl, Christoph Flamm, Philipp Kügler, James Lu, Stefan Müller, Peter Schuster

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Inverse Problems

Systems biology is a new discipline built upon the premise that an understanding of how cells and organisms carry out their functions cannot be gained by looking at cellular components in isolation. Instead, consideration of the interplay between the parts of systems is indispensable for analyzing, modeling, and predicting systems' behaviour.Studying biological processes under this premise, systems biology combines experimental techniques and computational methods in order to constructpredictive models. Both in building and utilizing models of biological systems, inverse problems arise at several occasions,for example, (i) when experimental time series and steady state data are used to construct biochemical reaction networks, (ii) when model parameters are identified that capture underlying mechanisms or (iii) when desired qualitative behaviour such as bistability or limit cycle oscillations is engineered by proper choices of parameter combinations.In this paper we review principles of the modelling process in systems biology and illustrate the ill-posedness and regularization of parameter identification problems in that context. Furthermore, we discuss the methodology of qualitative inverse problems and demonstrate how sparsity enforcing regularization allows the determination of key reaction mechanisms underlying the qualitative behaviour.

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