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J Bioinform Comput Biol. 2016 Feb;14(1):1640001. doi: 10.1142/S0219720016400011. Epub 2015 Nov 23.

A hybrid model of cell cycle in mammals.

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* Université Nice-Sophia Antipolis, I3S-UMR CNRS 7271, CS 40121, 06903 Sophia Antipolis Cedex, France.
† Université Nice Sophia Antipolis, CNRS UMR7277, INSERM U1091, Institut de Biologie Valrose, 06108 Nice, France.


Time plays an essential role in many biological systems, especially in cell cycle. Many models of biological systems rely on differential equations, but parameter identification is an obstacle to use differential frameworks. In this paper, we present a new hybrid modeling framework that extends René Thomas' discrete modeling. The core idea is to associate with each qualitative state "celerities" allowing us to compute the time spent in each state. This hybrid framework is illustrated by building a 5-variable model of the mammalian cell cycle. Its parameters are determined by applying formal methods on the underlying discrete model and by constraining parameters using timing observations on the cell cycle. This first hybrid model presents the most important known behaviors of the cell cycle, including quiescent phase and endoreplication.


Discrete modeling; hybrid modeling; mammalian cell cycle

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