Pauline Traynard1, Adrien Fauré2, François Fages3, Denis Thieffry1. 1. 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. 2. Graduate School of Science and Engineering, Yamaguchi University, Yamaguchi, Japan. 3. EPI Lifeware, Inria Inria Saclay Ile-de-France, Palaiseau, France.
Abstract
MOTIVATION: 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: 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). CONTACT: thieffry@ens.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: 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). CONTACT: thieffry@ens.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Aurélien Naldi; Céline Hernandez; Nicolas Levy; Gautier Stoll; Pedro T Monteiro; Claudine Chaouiya; Tomáš Helikar; Andrei Zinovyev; Laurence Calzone; Sarah Cohen-Boulakia; Denis Thieffry; Loïc Paulevé Journal: Front Physiol Date: 2018-06-19 Impact factor: 4.566
Authors: S Ha; E Dimitrova; S Hoops; D Altarawy; M Ansariola; D Deb; J Glazebrook; R Hillmer; H Shahin; F Katagiri; J McDowell; M Megraw; J Setubal; B M Tyler; R Laubenbacher Journal: BMC Bioinformatics Date: 2019-10-21 Impact factor: 3.169