A Model of the Cellular Iron Homeostasis Network Using Semi-Formal Methods for Parameter Space Exploration

Nicolas Mobilia
(UJF-Grenoble 1 / CNRS TIMC-IMAG UMR 5525 )
Alexandre Donzé
( University of California Berkeley, EECS Department)
Jean Marc Moulis
(UJF-Grenoble 1 / CNRS UMR 4952, Institut de Recherches en Technologies et Sciences pour le Vivant )
Éric Fanchon
(UJF-Grenoble 1 / CNRS TIMC-IMAG UMR 5525 )

This paper presents a novel framework for the modeling of biological networks. It makes use of recent tools analyzing the robust satisfaction of properties of (hybrid) dynamical systems. The main challenge of this approach as applied to biological systems is to get access to the relevant parameter sets despite gaps in the available knowledge. An initial estimate of useful parameters was sought by formalizing the known behavior of the biological network in the STL logic using the tool Breach. Then, once a set of parameter values consistent with known biological properties was found, we tried to locally expand it into the largest possible valid region. We applied this methodology in an effort to model and better understand the complex network regulating iron homeostasis in mammalian cells. This system plays an important role in many biological functions, including erythropoiesis, resistance against infections, and proliferation of cancer cells.

In Ezio Bartocci and Luca Bortolussi: Proceedings First International Workshop on Hybrid Systems and Biology (HSB 2012), Newcastle Upon Tyne, 3rd September 2012, Electronic Proceedings in Theoretical Computer Science 92, pp. 42–57.
Published: 15th August 2012.

ArXived at: http://dx.doi.org/10.4204/EPTCS.92.4 bibtex PDF
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