Modelling and analysis of biochemical signalling pathway cross-talk

Donaldson, R. and Calder, M. (2010) Modelling and analysis of biochemical signalling pathway cross-talk. Electronic Proceedings in Theoretical Computer Science, 19, pp. 40-54. (doi:10.4204/EPTCS.19.3)

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Abstract

Signalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising) parallel composition of instances of generic modules (with internal and external labels). Pathways are then composed by (synchronising) parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Calder, Professor Muffy
Authors: Donaldson, R., and Calder, M.
Subjects:Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Science and Engineering > School of Computing Science
Journal Name:Electronic Proceedings in Theoretical Computer Science
Publisher:Open Publishing Association
ISSN:2075-2180
Published Online:01 January 2010
Copyright Holders:Copyright © 2010 The Authors
First Published:First published in Electronic Proceedings in Theoretical Computer Science 19:40-54
Publisher Policy:Reproduced with the permission of the authors

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
436881The molecular noseAndrew PittEngineering & Physical Sciences Research Council (EPSRC)EP/E032745/2RI MOLECULAR CELL & SYSTEMS BIOLOGY