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Briefings in Bioinformatics Advance Access originally published online on November 20, 2006
Briefings in Bioinformatics 2006 7(4):339-353; doi:10.1093/bib/bbl043
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© The Author 2006. Published by Oxford University Press. For Permissions, please email: journals.permissions@oxfordjournals.org

Computational methodologies for modelling, analysis and simulation of signalling networks

David Gilbert, Hendrik Fuß, Xu Gu, Richard Orton, Steve Robinson, Vladislav Vyshemirsky, Mary Jo Kurth, C. Stephen Downes and Werner Dubitzky

Corresponding author. Prof. David Gilbert, Bioinformatics Research Centre, A416, Davidson Building University of Glasgow, Glasgow G12 8QQ, Scotland, UK. Tel: +44 141 330 2563; Fax: +44 141 330 8627; E-mail: drg{at}dcs.gla.ac.uk

This article is a critical review of computational techniques used to model, analyse and simulate signalling networks. We propose a conceptual framework, and discuss the role of signalling networks in three major areas: signal transduction, cellular rhythms and cell-to-cell communication. In order to avoid an overly abstract and general discussion, we focus on three case studies in the areas of receptor signalling and kinase cascades, cell-cycle regulation and wound healing. We report on a variety of modelling techniques and associated tools, in addition to the traditional approach based on ordinary differential equations (ODEs), which provide a range of descriptive and analytical powers. As the field matures, we expect a wider uptake of these alternative approaches for several reasons, including the need to take into account low protein copy numbers and noise and the great complexity of cellular organisation. An advantage offered by many of these alternative techniques, which have their origins in computing science, is the ability to perform sophisticated model analysis which can better relate predicted behaviour and observations.

Keywords: biochemical signalling networks, modelling, analysis, simulation


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