Quantitative Biology

   

Logical Modeling of the Mammalian Cell Cycle

Authors: Pauline Traynard, Adrien Fauré, François Fages, Denis Thieffry

Proper understanding of the behavior of complex biological regulatory networks requires the integration of heterogeneous data into predictive mathematical models. Logical modeling focuses on qualitative data and offers a flexible framework to delineate the main dynamical properties of such networks. However, formal analysis faces a combinatorial explosion as the number of regulatory components and interactions increases. Here, we show how model-checking techniques can be used to verify sophisticated dynamical properties resulting from model regulatory structure. We demonstrate the power of this approach through the updating of a model of the molecular network controlling mammalian cell cycle. We use model-checking to progressively refine this model in order to fit recent experimental observations. The resulting model accounts for the sequential activation of cyclins, the role of Skp2, and emphasizes a multifunctional role for the cell cycle inhibitor Rb.

Comments: 14 Pages.

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[v1] 2015-12-16 09:16:24

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