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)

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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
43688	1	The molecular nose	Andrew Pitt	Engineering & Physical Sciences Research Council (EPSRC)	EP/E032745/2	RI MOLECULAR CELL & SYSTEMS BIOLOGY