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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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Modular model of TNFalpha cytotoxicity

Chignola, Roberto and Vyshemirsky, Vladislav and Farina, Marcello and Del Fabbro, Alessio and Milotti, Edoardo (2011) Modular model of TNFalpha cytotoxicity. Bioinformatics, 27 (13). pp. 1754-1757. ISSN 1367-4803

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Abstract

Tumour Necrosis Factor alpha (TNF) initiates a complex series of biochemical events in the cell upon binding to its type R1 receptor (TNF-R1). Recent experimental work has unravelled the molecular regulation of the signalling complexes that lead either to cell survival or death. Survival signals are activated by direct binding of TNF to TNF-R1 at the cell membrane whereas apoptotic signals by endocytosed TNF/TNF-R1 complexes. Here we describe a reduced, effective model with few free parameters, where we group some intricate mechanisms into effective modules, that successfully describes this complex set of actions. We study the parameter space to show that the model is structurally stable and robust over a broad range of parameter values. We use state-of-the-art Bayesian methods (a Sequential Monte Carlo sampler) to perform inference of plausible values of the model parameters from experimental data. As a result, we obtain a robust model that can provide a solid basis for further modelling of TNF signalling. The model is also suitable for inclusion in multi-scale simulation programs that are presently under development to study the behaviour of large tumour cell populations. We provide supplementary material that includes all mathematical details and all algorithms (Matlab code) and models (SBML descriptions).