title: Logical model specification aided by model-checking techniques: application to the mammalian cell cycle regulation.
abstract: Understanding the temporal behaviour of biological regulatory networks requires the integration of molecular information into a formal model. However, the analysis of model dynamics faces a combinatorial explosion as the number of regulatory components and interactions increases.
  
  
  
  We use model-checking techniques to verify sophisticated dynamical properties resulting from the model regulatory structure in the absence of kinetic assumption. We demonstrate the power of this approach by analysing a logical model of the molecular network controlling mammalian cell cycle. This approach enables a systematic analysis of model properties, the delineation of model limitations, and the assessment of various refinements and extensions based on recent experimental observations. The resulting logical model accounts for the main irreversible transitions between cell cycle phases, the sequential activation of cyclins, and the inhibitory role of Skp2, and further emphasizes the multifunctional role for the cell cycle inhibitor Rb.
  
  
  
  The original and revised mammalian cell cycle models are available in the model repository associated with the public modelling software GINsim (http://ginsim.org/node/189).
  
  
  
  thieffry@ens.fr
  
  
  
  Supplementary data are available at Bioinformatics online.
authors: Computational Systems Biology Team, Institut de Biologie de L'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France EPI Lifeware, Inria Inria Saclay Ile-de-France, Palaiseau, France.
authors: Pauline
authors: P
authors: Traynard
authors: Graduate School of Science and Engineering, Yamaguchi University, Yamaguchi, Japan.
authors: Adrien
authors: A
authors: Fauré
authors: EPI Lifeware, Inria Inria Saclay Ile-de-France, Palaiseau, France.
authors: François
authors: F
authors: Fages
authors: Computational Systems Biology Team, Institut de Biologie de L'Ecole Normale Supérieure (IBENS), CNRS, Inserm, Ecole Normale Supérieure, PSL Research University, Paris, France EPI Lifeware, Inria Inria Saclay Ile-de-France, Palaiseau, France.
authors: Denis
authors: D
authors: Thieffry
mesh_terms: D000818:Animals; D002453:Cell Cycle; D003198:Computer Simulation; D006801:Humans; D008128:Logic; D008322:Mammals; D008954:Models, Biological; D012984:Software