Skip to main content

Analysis of Signalling Pathways Using Continuous Time Markov Chains

  • Conference paper
Transactions on Computational Systems Biology VI

Part of the book series: Lecture Notes in Computer Science ((TCSB,volume 4220))

Abstract

We describe a quantitative modelling and analysis approach for signal transduction networks.

We illustrate the approach with an example, the RKIP inhibited ERK pathway [CSK + 03]. Our models are high level descriptions of continuous time Markov chains: proteins are modelled by synchronous processes and reactions by transitions. Concentrations are modelled by discrete, abstract quantities. The main advantage of our approach is that using a (continuous time) stochastic logic and the PRISM model checker, we can perform quantitative analysis such as what is the probability that if a concentration reaches a certain level, it will remain at that level thereafter? or how does varying a given reaction rate affect that probability? We also perform standard simulations and compare our results with a traditional ordinary differential equation model. An interesting result is that for the example pathway, only a small number of discrete data values is required to render the simulations practically indistinguishable.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aziz, A., Sanwal, K., Singhal, V., Brayton, R.: Model checking continuous time markov chains. ACM Transactions on Computational Logic 1, 162–170 (2000)

    Article  MathSciNet  Google Scholar 

  2. Baier, C., Haverkort, B., Hermanns, H., Katoen, J.-P.: Model checking continuous-time Markov chains by transient analysis. In: CAV (2000)

    Google Scholar 

  3. Chabrier, N., Fages, F.: Symbolic model checking of biochemical networks. In: Priami, C. (ed.) CMSB 2003. LNCS, vol. 2602, pp. 149–162. Springer, Heidelberg (2003)

    Chapter  Google Scholar 

  4. Calder, M., Gilmore, S., Hillston, J.: Modelling the influence of RKIP on the ERK signalling pathway using the stochastic process algebra PEPA. In: Proceedings of Bio-Concur 2004 (2004)

    Google Scholar 

  5. Chabrier-Rivier, N., Chiaverini, M., Danos, V., Fages, F., Schchter, V.: Modeling and querying biomolecular interaction networks. Theoretical Computer Science 325(1), 25–44 (2004)

    Article  MATH  MathSciNet  Google Scholar 

  6. Cho, K.-H., Shin, S.-Y., Kim, H.-W., Wolkenhauer, O., McFerran, B., Kolch, W.: Mathematical modeling of the influence of RKIP on the ERK signaling pathway. In: Priami, C. (ed.) CMSB 2003. LNCS, vol. 2602, pp. 127–141. Springer, Heidelberg (2003)

    Chapter  Google Scholar 

  7. Gillespie, D.: Exact stochastic simulation of coupled chemical reactions. The Journal of Physical Chemistry 81(25), 2340–2361 (1977)

    Article  Google Scholar 

  8. Goss, P.J.E., Peccoud, J.: Quantitative modeling of stochastic systems in molecular biology by using stochastic Petri nets. In: Proc. Natl. Acad. Sci. USA (Biochemistry), vol. 95, pp. 6750–6755 (1998)

    Google Scholar 

  9. Kholodenko, B.N., Demin, O.V., Moehren, G., Hoek, J.B.: Quantification of short term signaling by the epidermal growth factor receptor. The Journal of Biological Chemistry 274(42), 30169–30181 (1999)

    Article  Google Scholar 

  10. Koch, I., Heiner, M.: Qualitative modelling and analysis of biochemical pathways with petri nets. In: Tutorial Notes, 5th Int. Conference on Systems Biology - ICSB 2004, Heidelberg/Germany (October 2004)

    Google Scholar 

  11. Kwiatkowska, M., Norman, G., Parker, D.: PRISM: Probabilistic symbolic model checker. In: Field, T., Harrison, P.G., Bradley, J., Harder, U. (eds.) TOOLS 2002. LNCS, vol. 2324, pp. 200–204. Springer, Heidelberg (2002)

    Google Scholar 

  12. Matsuno, H., Doi, A., Nagasaki, M., Miyano, S.: Hybrid petri net representation of gene regulatory network. Pacific Symposium on Biocomputing 5, 341–352 (2000)

    Google Scholar 

  13. Parker, D., Norman, G., Kwiatkowska, M.: PRISM 2.1 Users’ Guide. In: The University of Birmingham (September 2004)

    Google Scholar 

  14. PRISM Web page, http://www.cs.bham.ac.uk/~dxp/prism/

  15. Priami, C., Regev, A., Silverman, W., Shapiro, E.: Application of a stochastic name passing calculus to representation and simulation of molecular processes. Information Processing Letters 80, 25–31 (2001)

    Article  MATH  MathSciNet  Google Scholar 

  16. Pinney, J.W., Westhead, D.R., McConkey, G.A.: Petri Net representations in systems biology. Biochem. Soc. Trans. 31, 1513–1515 (2003)

    Article  Google Scholar 

  17. Popova-Zeugmann, L., Heiner, M., Koch, I.: Modelling and analysis of biochemical networks with time petri nets. Informatik-Berichte der HUB Nr. 170 1(170), 136–143 (2004)

    Google Scholar 

  18. Regev, A., Silverman, W., Shapiro, E.: Representation and simulation of biochemical processes using π-calculus process algebra. In: Pacific Symposium on Biocomputing 2001 (PSB 2001), pp. 459–470 (2001)

    Google Scholar 

  19. Schoeberl, B., Eichler-Jonsson, C., Gilles, E.D., Muller, G.: Computational modelling of the dynamics of the map kinase cascade activated by surface and internalised egf receptors. Nature Biotechnology 20, 370–375 (2002)

    Article  Google Scholar 

  20. Voit, E.O.: Computational Analysis of Biochemical Systems. Cambridge University Press, Cambridge (2000)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Calder, M., Vyshemirsky, V., Gilbert, D., Orton, R. (2006). Analysis of Signalling Pathways Using Continuous Time Markov Chains. In: Priami, C., Plotkin, G. (eds) Transactions on Computational Systems Biology VI. Lecture Notes in Computer Science(), vol 4220. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11880646_3

Download citation

  • DOI: https://doi.org/10.1007/11880646_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-45779-4

  • Online ISBN: 978-3-540-46236-1

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics