title: Composition and abstraction of logical regulatory modules: application to multicellular systems.
abstract: BACKGROUND
  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.
authors: IGC, Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, P-2780-156 Oeiras, Portugal.
authors: Nuno D
authors: ND
authors: Mendes
authors: Frédéric
authors: F
authors: Lang
authors: Yves-Stan
authors: YS
authors: Le Cornec
authors: Radu
authors: R
authors: Mateescu
authors: Gregory
authors: G
authors: Batt
authors: Claudine
authors: C
authors: Chaouiya
mesh_terms: D000465:Algorithms; D019521:Body Patterning; D002450:Cell Communication; D019295:Computational Biology / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein