Composition and abstraction of logical regulatory modules: application to multicellular systems

Bioinformatics. 2013 Mar 15;29(6):749-57. doi: 10.1093/bioinformatics/btt033. Epub 2013 Jan 22.

Abstract

Motivation: Logical (Boolean or multi-valued) modelling is widely used to study regulatory or signalling networks. Even though these discrete models constitute a coarse, yet useful, abstraction of reality, the analysis of large networks faces a classical combinatorial problem. Here, we propose to take advantage of the intrinsic modularity of inter-cellular networks to set up a compositional procedure that enables a significant reduction of the dynamics, yet preserving the reachability of stable states. To that end, we rely on process algebras, a well-established computational technique for the specification and verification of interacting systems.

Results: We develop a novel compositional approach to support the logical modelling of interconnected cellular networks. First, we formalize the concept of logical regulatory modules and their composition. Then, we make this framework operational by transposing the composition of logical modules into a process algebra framework. Importantly, the combination of incremental composition, abstraction and minimization using an appropriate equivalence relation (here the safety equivalence) yields huge reductions of the dynamics. We illustrate the potential of this approach with two case-studies: the Segment-Polarity and the Delta-Notch modules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Body Patterning
  • Cell Communication
  • Computational Biology / methods
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Models, Biological*
  • Receptors, Notch / metabolism
  • Signal Transduction*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch
  • delta protein