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Modeling Multi-valued Genetic Regulatory Networks Using High-Level Petri Nets.

Comet, Jean-Paul; Klaudel, Hanna; Liauzu, Stéphane

In: Gianfranco Ciardo, Philippe Darondeau (Eds.): Lecture Notes in Computer Science, Vol. 3536: Applications and Theory of Petri Nets 2005: 26th International Conference, ICATPN 2005, Miami, USA, June 20-25, 2005., pages 208-227. Springer Verlag, June 2005.

Abstract: Regulatory networks are at the core of all biological functions from bio-chemical pathways to gene regulation and cell communication processes. Because of the complexity of the interweaving retroactions, the overall behavior is difficult to grasp and the development of formal methods is needed in order to confront the supposed properties of the biological system to the model. We revisit here the tremendous work of R. Thomas and show that its binary and also its multi-valued approach can be expressed in a unified way with high-level Petri nets. A compact modeling of genetic networks is proposed in which the tokens represent gene's expression levels and their dynamical behavior depends on a certain number of biological parameters. This allows us to take advantage of techniques and tools in the field of high-level Petri nets. A developed prototype allows a biologist to verify systematically the coherence of the system under various hypotheses. These hypotheses are translated into temporal logic formulae and the model-checking techniques are used to retain only the models whose behavior is coherent with the biological knowledge.

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