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On parametric sensitivity and structural robustness of cellular functions - The oscillatory metabolism of activated Neutrophils
KTH, School of Electrical Engineering (EES), Automatic Control.
2005 (English)In: 2005 44th IEEE Conference on Decision and Control & European Control Conferenc, 2005, 3681-3686 p.Conference paper, Published paper (Refereed)
Abstract [en]

Robustness of cellular functions is a key property of living organisms. Modelling and analysis of the genetic and biochemical networks underlying specific functions will enable quantification of the robustness as well as identification of the specific mechanisms providing robustness. Studies on cellular robustness has so far largely focused on parametric sensitivities, i.e., robustness of functions (behavior) with respect to changes in model parameters. In this paper we argue that robustness analysis of cellular models also should encompass structural robustness, i.e., robustness with respect to perturbations in the model structure. This is important not only to quantify the robustness of the cell functions themselves, but equally important, to gain knowledge about the quality of the model as such. In particular, if the model displays poor robustness against structural perturbations this serves as an indication of a potentially highly uncertain model and hence care must be exercised when interpreting the obtained parametric sensitivities. We here propose a simple method for analysing structural robustness of functions related to bistability and periodic oscillations in intracellular networks. The method is applied to a model of the oscillatory metabolism of activated neutrophils (white blood cells) recently proposed in Olsen et al., Biophys J, 84:69-81, 2003. The model is found to be highly robust against parametric uncertainties, but is shown to display poor structural robustness. Indeed, attempting to divide the model into compartments, with the aim of emulating spatial distributions that exist in vivo, results in a qualitatively different model prediction.

Place, publisher, year, edition, pages
2005. 3681-3686 p.
Series
IEEE CONFERENCE ON DECISION AND CONTROL - PROCEEDINGS, ISSN 0191-2216
National Category
Control Engineering
Identifiers
URN: urn:nbn:se:kth:diva-26565DOI: 10.1109/CDC.2005.1582734ISI: 000240653703097Scopus ID: 2-s2.0-33847222500OAI: oai:DiVA.org:kth-26565DiVA: diva2:384588
Conference
44th IEEE Conference on Decision Control/European Control Conference (CCD-ECC) Seville, SPAIN, DEC 12-15, 2005
Note
QC 20110110Available from: 2011-01-10 Created: 2010-11-25 Last updated: 2011-01-10Bibliographically approved

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