Modeling biological pathway dynamics with timed automata

Stefano Schivo, Jetse Scholma, Brend Wanders, Ricardo A Urquidi Camacho, Paul E van der Vet, Marcel Karperien, Rom Langerak, Jaco van de Pol, Janine N Post

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Living cells are constantly subjected to a plethora of environmental stimuli that require integration into an appropriate cellular response. This integration takes place through signal transduction events that form tightly interconnected networks. The understanding of these networks requires capturing their dynamics through computational support and models. ANIMO (analysis of Networks with Interactive Modeling) is a tool that enables the construction and exploration of 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 analyzed via the UPPAAL model checker. Thanks to Timed Automata, we can provide a formal semantics for the domain-specific language used to represent signaling networks. This enforces precision and uniformity in the definition of signaling pathways, contributing to the integration of isolated signaling events into complex network models. We propose an approach to discretization of reaction kinetics that allows us to efficiently use UPPAAL as the computational engine to explore the dynamic behavior of the network of interest. A user-friendly interface hides the use of Timed Automata from the user, while keeping the expressive power intact. Abstraction to single-parameter kinetics speeds up construction of models that remain faithful enough to provide meaningful insight. The resulting dynamic behavior of the network components is displayed graphically, allowing for an intuitive and interactive modeling experience.

Original languageEnglish
Pages (from-to)832-839
Number of pages8
JournalIEEE Journal of Biomedical and Health Informatics
Volume18
Issue number3
DOIs
Publication statusPublished - May 2014
Externally publishedYes

Keywords

  • Animals
  • Models, Biological
  • PC12 Cells
  • Rats
  • Signal Transduction/genetics
  • Systems Biology/methods
  • User-Computer Interface

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