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

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

Original languageEnglish
Title of host publicationTransactions on Computational Systems Biology XII
Subtitle of host publicationSpecial Issue on Modeling Methodologies
PublisherSpringer-Verlag GmbH
Pages229-262
Number of pages34
VolumeXII
ISBN (Print)978-3-642-11711-4
DOIs
Publication statusPublished - 2010

Publication series

NameLecture Notes in Computer Science
PublisherSpringer Berlin / Heidelberg
Volume5945
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

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.

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