Modelling and analysis of the NF-κB pathway in bio-PEPA

  • Authors:

  • Federica Ciocchetta;Andrea Degasperi;John K. Heath;Jane Hillston

  • Affiliations:

  • Microsoft Research - University of Trento Centre for Computational and Systems Biology, Trento, Italy;Department of Computing Science, University of Glasgow, UK;School of Biosciences, University of Birmingham, UK;Laboratory for Foundations of Computer Science, University of Edinburgh, UK

  • Venue:
  • Transactions on Computational Systems Biology XII
  • Year:
  • 2010

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Abstract

In this work we present a Bio-PEPA model describing the Nuclear Factor κB (NF-κB) signalling pathway. In particular our model focuses on the dynamic response of NF-κB to an external stimulus. Each biochemical species in the pathway is represented by a specific Bio-PEPA component and the external stimulus is abstracted by time-dependent Bio-PEPA events describing the start and the end of the signal. The Bio-PEPA model is a formal intermediate representation of the pathway on which various kinds of analysis can be performed. Both stochastic and deterministic simulations are carried out to validate our model against the experimental data and in-silico experiments in the literature and to verify some properties, such as, the impact of the duration of the external stimulus and of the total NF-κB initial amount on the behaviour of some species of interest. Furthermore we use stochastic simulation to compare the behaviour of the single cell against the average behaviour of a population of cells. Finally, sensitivity analysis is considered to investigate the most influential parameters of the model. Importantly, the approach taken suggests that the sensitivity of some parameters alters with the time evolution of the pathway.