Modelling biological pathway dynamics with Timed Automata

• Main Authors: Schivo, S., Scholma, J., Wanders, B., Camacho, R. A. U., van der Vet, P. E., Karperien, M., Langerak, R., van de Pol, J., Post, J. N.
• Format: Conference Proceeding
• Language: English
• Subjects: Analytical models; Automata; Biological system modeling; Computational modeling; Data models; dynamic behaviour; Kinetic theory; modelling; signalling pathway; timed automata
• DOI: 10.1109/BIBE.2012.6399719

When analysing complex interaction networks occurring in biological cells, a biologist needs computational support in order to understand the effects of signalling molecules (e.g. growth factors, drugs). ANIMO (Analysis of Networks with Interactive MOdelling) is a tool that allows the user to create and explore executable models of biological networks, helping to derive hypotheses and to plan wet-lab experiments. The tool is based on the formalism of Timed Automata, which can be analysed via the UPPAAL model checker. Thanks to Timed Automata, we can provide a formal semantics for the domain-specific language used to represent signalling networks. This enforces precision and uniformity in the definition of signalling pathways, contributing to the integration of signalling event models into complex, crosstalk-driven networks. We propose an approach to discretization of reaction kinetics that allows us to efficiently use UPPAAL as the computational engine to explore the dynamic cell behaviour. A user friendly interface makes the use of Timed Automata completely transparent to the biologist, while keeping the expressive power intact. This allows to define relatively simple, yet faithful models of complex biological interactions. The resulting timed behaviour is displayed graphically, allowing for an intuitive and interactive modelling experience.