A methodology for global-sensitivity analysis of time-dependent outputs in systems biology modelling

Sumner, T; Shephard, E; Bogle, IDL; (2012) A methodology for global-sensitivity analysis of time-dependent outputs in systems biology modelling. Journal of the Royal Society, Interface / the Royal Society, 9 (74). pp. 2156-2166. ISSN 1742-5689 DOI: https://doi.org/10.1098/rsif.2011.0891

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One of the main challenges in the development of mathematical and computational models of biological systems is the precise estimation of parameter values. Understanding the effects of uncertainties in parameter values on model behaviour is crucial to the successful use of these models. Global sensitivity analysis (SA) can be used to quantify the variability in model predictions resulting from the uncertainty in multiple parameters and to shed light on the biological mechanisms driving system behaviour. We present a new methodology for global SA in systems biology which is computationally efficient and can be used to identify the key parameters and their interactions which drive the dynamic behaviour of a complex biological model. The approach combines functional principal component analysis with established global SA techniques. The methodology is applied to a model of the insulin signalling pathway, defects of which are a major cause of type 2 diabetes and a number of key features of the system are identified.

Item Type: Article
Keywords: sensitivity analysis, computational modelling, insulin signalling, insulin-resistance, signaling pathway, screening design, oscillations, transduction, phosphatases, mechanism, networks, obesity, kinase
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 22491976
Web of Science ID: 306750500012
URI: http://researchonline.lshtm.ac.uk/id/eprint/251162


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