Picture of person typing on laptop with programming code visible on the laptop screen

World class computing and information science research at Strathclyde...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including by researchers from the Department of Computer & Information Sciences involved in mathematically structured programming, similarity and metric search, computer security, software systems, combinatronics and digital health.

The Department also includes the iSchool Research Group, which performs leading research into socio-technical phenomena and topics such as information retrieval and information seeking behaviour.

Explore

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

Full text not available in this repository. Request a copy from the Strathclyde author

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).