Logical modeling of the mammalian cell cycle
Pauline Traynard, Adrien Fauré, François Fages, Denis Thieffry · HAL (Le Centre pour la Communication Scientifique Directe) · 2015
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.