Modular modelling of signalling pathways and their cross-talk

Signalling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals. Collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signalling behaviours. While there are several formal modelling approaches for signalling pathways, none make cross-talk explicit; the aim of this paper is to define and categorise cross-talk in a rigorous way. We define a modular approach to pathway and network modelling, based on the module construct in the PRISM modelling language, and a set of generic signalling modules. Five different types of cross-talk are defined according to various biologically meaningful combinations of variable sharing, synchronisation labels and reaction renaming. The approach is illustrated with a case-study analysis of cross-talk between the TGF-beta, WNT and MAPK pathways. (C) 2012 Elsevier B.V. All rights reserved.