Robustification as a tool in modeling biochemical reaction networks
2010 (English)In: Proceedings of IFAC DYCOPS 2010, Leuven, Belgium, 2010, 338-343 p.Conference paper (Refereed)
Biological functions have evolved to become robust against a multitude of perturbations such as gene mutations, intracellular noise and changes in the physical and chemical environment. This robustness should be reflected in models of the underlying biochemical networks, and robustness analysis is frequently employed in validating models of intracellular biochemical reaction networks. However, at present there are no tools or guidelines available to support postulation of model modifications that can serve to improve the robustness. Herein we propose a method based on computing the sensitivity of the robustness with respect to generic dynamic perturbations applied to the individual network edges. To quantify robustness we compute the smallest simultaneous change in the activity of the network nodes that induces a bifurcation in the network, resulting in a qualitative change in the network behavior. The focus is on biological functions related to bistable switches and sustained oscillations, and the proposed methodology is demonstrated through application to metabolic oscillations in white blood cells and bistable switching in MAPK signal transduction.
Place, publisher, year, edition, pages
2010. 338-343 p.
, IFAC Proceedings Volumes (IFAC-PapersOnline), ISSN 1474-6670 ; Volume 9, Issue Part 1
Bifurcations, Biochemical networks, Dynamic behavior, Gene regulatory networks, Modeling, Robustness, Systems biology
Bioinformatics and Systems Biology Control Engineering
IdentifiersURN: urn:nbn:se:kth:diva-88067DOI: 10.3182/20100705-3-BE-2011.0169ScopusID: 2-s2.0-80051720501ISBN: 978-390266169-2OAI: oai:DiVA.org:kth-88067DiVA: diva2:502097
9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010; Leuven; Belgium; 5 July 2010 through 7 July 2010
FunderSwedish Research Council
QC 201202192012-02-142012-02-142014-09-03Bibliographically approved