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Linear systems approach to analysis of complex dynamic behaviours in biochemical networks
KTH, School of Electrical Engineering (EES), Automatic Control.
KTH, School of Electrical Engineering (EES), Automatic Control.
2004 (English)In: IEE Proceedings - Systems Biology, ISSN 1741-2471, E-ISSN 1741-248X, Vol. 1, no 1, 149-158 p.Article in journal (Refereed) Published
Abstract [en]

Central functions in the cell are often linked to complex dynamic behaviours, such as sustained oscillations and multistability, in a biochemical reaction network. Determination of the specific mechanisms underlying such behaviours isimportant, e.g. to determine sensitivity, robustness, and modelling requirements of given cell functions. In this work we adopt a systems approach to the analysis of complex behaviours in intracellular reaction networks, described byordinary differential equations with known kinetic parameters. We propose to decompose the overall system into a number of low complexity subsystems, and consider the importance of interactions between these in generating specific behaviours. Rather than analysing the network in a state corresponding to the complex non-linear behaviour, we move the system to the underlying unstable steady state, and focus on the mechanisms causing destabilisation of this steady state. This is motivated by the fact that all complex behaviours in unforced systems can be traced to destabilisation (bifurcation) of some steady state, andhence enables us to use tools from linear system theory to qualitatively analyse the sources of given network behaviours. One important objective of the present study is to see how far one can come with a relatively simple approach to the analysis of highly complex biochemical networks. The proposed method is demonstrated by application to a model of mitotic control in Xenopus frog eggs, and to a model of circadian oscillations in Drosophila. In both examples we are able to identify the subsystems, and the related interactions, which are instrumental in generating the observed complex non-linear behaviours.

Place, publisher, year, edition, pages
2004. Vol. 1, no 1, 149-158 p.
National Category
Cell and Molecular Biology
URN: urn:nbn:se:kth:diva-44854DOI: 10.1049/sb:20045015ISI: 000231503900020ScopusID: 2-s2.0-32544450571OAI: diva2:451569
QC 20111026Available from: 2011-10-26 Created: 2011-10-25 Last updated: 2011-10-26Bibliographically approved

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