Formal Analysis of the Genetic Toggle

  • Authors:
  • Giampaolo Bella;Pietro Liò

  • Affiliations:
  • Dipartimento di Matematica e Informatica, Università di Catania, Catania, Italy 95125;Computer Laboratory, University of Cambridge, Cambridge, UK CB3 0FD

  • Venue:
  • CMSB '09 Proceedings of the 7th International Conference on Computational Methods in Systems Biology
  • Year:
  • 2009

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Abstract

The formal analysis of the toggle switch, which is among the most common motifs of genetic networks, shows that along with the powerful development of mathematical modelling, formal methods can be of great help in investigating the properties of genetic networks. In particular, a general approach to modelling genetic networks through the language of higher-order logic is advanced and mechanised in the theorem prover Isabelle. An inductive definition provides a formal model for the genetic toggle as the set of all possible evolutions of such network. Gene polymerase and protein concentration are formalised as primitive recursive functions. The main properties of the genetic toggle are confirmed upon the model: it is possible that one protein exceeds a stated concentration threshold and the other protein does not; it is impossible that both proteins exceed their respective concentration thresholds at the same time. To the best of the authors' knowledge, this is the first contribution of theorem proving in the area of genetic network analysis, and as such may set the foundations for a new niche of research.