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Modelling and Analysis of the NF-κB Pathway in Bio-PEPA

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Transactions on Computational Systems Biology XII

Part of the book series: Lecture Notes in Computer Science ((TCSB,volume 5945))

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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Author information

Authors and Affiliations

  1. Microsoft Research - University of Trento Centre for Computational and Systems Biology, Trento, Italy

    Federica Ciocchetta

  2. Department of Computing Science, University of Glasgow, G12 8QQ, UK

    Andrea Degasperi

  3. School of Biosciences, University of Birmingham, B15 2TT, UK

    John K. Heath

  4. Laboratory for Foundations of Computer Science, University of Edinburgh, EH8 9AB, UK

    Jane Hillston

  5. Centre for Systems Biology at Edinburgh (CSBE), Edinburgh, Scotland

    Jane Hillston

Authors
  1. Federica Ciocchetta
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  2. Andrea Degasperi
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  3. John K. Heath
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  4. Jane Hillston
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Editor information

Editors and Affiliations

  1. Centre for Computational and Systems Biology, The Microsoft Research - University of Trento, Piazza Manci, 17, 38050, Povo (TN), Italy

    Corrado Priami

  2. Groningen Bioinformatics, University of Groningen, Centre, Kerklaan 30, 9751 NN, Haren, The Netherlands

    Rainer Breitling

  3. School of Information Systems, Brunel University, Kingston Lane, UB8 3PH, Uxbridge, UK

    David Gilbert

  4. Computer Science Institute, Brandenburg University of Technology, Walther-Pauer-Str. 2, 03046, Cottbus, Germany

    Monika Heiner

  5. Institute of Computer Science, University of Rostock, Joachim-Jungius-Str.10, 18059, Rostock, Germany

    Adelinde M. Uhrmacher

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Ciocchetta, F., Degasperi, A., Heath, J.K., Hillston, J. (2010). Modelling and Analysis of the NF-κB Pathway in Bio-PEPA. In: Priami, C., Breitling, R., Gilbert, D., Heiner, M., Uhrmacher, A.M. (eds) Transactions on Computational Systems Biology XII. Lecture Notes in Computer Science(), vol 5945. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11712-1_7

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  • DOI: https://doi.org/10.1007/978-3-642-11712-1_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-11711-4

  • Online ISBN: 978-3-642-11712-1

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