Skip to main content

A Model Checking Approach to the Parameter Estimation of Biochemical Pathways

  • Conference paper
Book cover Computational Methods in Systems Biology (CMSB 2008)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 5307))

Included in the following conference series:

Abstract

Model checking has historically been an important tool to verify models of a wide variety of systems. Typically a model has to exhibit certain properties to be classed ‘acceptable’. In this work we use model checking in a new setting; parameter estimation. We characterise the desired behaviour of a model in a temporal logic property and alter the model to make it conform to the property (determined through model checking). We have implemented a computational system called MC2(GA) which pairs a model checker with a genetic algorithm. To drive parameter estimation, the fitness of set of parameters in a model is the inverse of the distance between its actual behaviour and the desired behaviour. The model checker used is the simulation-based Monte Carlo Model Checker for Probabilistic Linear-time Temporal Logic with numerical constraints, MC2(PLTLc). Numerical constraints as well as the overall probability of the behaviour expressed in temporal logic are used to minimise the behavioural distance. We define the theory underlying our parameter estimation approach in both the stochastic and continuous worlds. We apply our approach to biochemical systems and present an illustrative example where we estimate the kinetic rate constants in a continuous model of a signalling pathway.

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. Wolkenhauer, O.: Systems Biology: the Reincarnation of Systems Theory Applied in Biology? Briefings in Bioinformatics 2(3), 258–270 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. Kolch, W., Calder, M., Gilbert, D.: When kinases meet mathematics: the systems biology of MAPK signalling. FEBS Lett. 579, 1891–1895 (2005)

    Article  CAS  PubMed  Google Scholar 

  3. Gilbert, D., Heiner, M., Lehrack, S.: A unifying framework for modelling and analysing biochemical pathways using Petri nets. In: Calder, M., Gilmore, S. (eds.) CMSB 2007. LNCS (LNBI), vol. 4695, pp. 200–216. Springer, Heidelberg (2007)

    Chapter  Google Scholar 

  4. Vyshemirsky, V., Girolami, M.: Bayesian Ranking of Biochemical System Models. Bioinformatics 24(6), 833–839 (2008)

    Article  CAS  PubMed  Google Scholar 

  5. Maria, G.: A Review of Algorithms and Trends in Kinetic Model Identification for Chemical and Biochemical Systems. Chem. Biochem. Eng. Q. 18(3), 195–222 (2004)

    CAS  Google Scholar 

  6. Donaldson, R., Gilbert, D.: A Monte Carlo Model Checker for Probabilistic LTL with Numerical Constraints. Technical report, University of Glasgow, Department of Computing Science (2008)

    Google Scholar 

  7. Baier, C.: On Algorithmic Verification Methods for Probabilistic Systems. Habilitation thesis, University of Mannheim (1998)

    Google Scholar 

  8. Brightman, F., Fell, D.: Differential feedback regulation of the mapk cascade underlies the quantitative differences in egf and ngf signalling in pc12 cells. FEBS Lett. 482, 169–174 (2000)

    Article  CAS  PubMed  Google Scholar 

  9. Gilbert, D., Heiner, M., Rosser, S., Fulton, R., Gu, X., Trybilo, M.: A Case Study in Model-driven Synthetic Biology. In: Biologically Inspired Cooperative Computing: BICC 2008. IFIP, vol. 268, pp. 163–175. Springer, Heidelberg (2008)

    Chapter  Google Scholar 

  10. Pnueli, A.: The Temporal Semantics of Concurrent Programs. Theor. Comput. Sci. 13, 45–60 (1981)

    Article  Google Scholar 

  11. Clarke, E.M., Grumberg, O., Peled, D.A.: Model Checking. MIT Press, Cambridge (1999) (third printing, 2001)

    Google Scholar 

  12. Fages, F., Rizk, A.: On the Analysis of Numerical Data Time Series in Temporal Logic. In: Calder, M., Gilmore, S. (eds.) CMSB 2007. LNCS (LNBI), vol. 4695, pp. 48–63. Springer, Heidelberg (2007)

    Chapter  Google Scholar 

  13. Hansson, H., Jonsson, B.: A Logic for Reasoning about Time and Reliability. Formal Aspects of Computing 6(5), 512–535 (1994)

    Article  Google Scholar 

  14. Aziz, A., Sanwal, K., Singhal, V., Brayton, R.K.: Verifying Continuous-Time Markov Chains. In: Alur, R., Henzinger, T.A. (eds.) CAV 1996. LNCS, vol. 1102, pp. 269–276. Springer, Heidelberg (1996)

    Chapter  Google Scholar 

  15. Goldberg, D.E.: Genetic Algorithms in Search, Optimization and Machine Learning. Addison-Wesley Longman Publishing Co., Inc., Boston (1989)

    Google Scholar 

  16. BioNessie: A Biochemical Pathway Simulation and Analysis Tool. University of Glasgow, http://www.bionessie.org

  17. MC2(PLTLc) Website: MC2(PLTLc) - PLTLc model checker. University of Glasgow (2008), http://www.brc.dcs.gla.ac.uk/software/mc2/

  18. Meffert, K., et al.: JGAP - Java Genetic Algorithms and Genetic Programming Package (2008), http://jgap.sf.net/

  19. Hucka, M., Finney, A., Sauro, H.M., Bolouri, H., Doyle, J.C., Kitano, H., et al.: The systems biology markup language (SBML): A medium for representation and exchange of biochemical network models. J. Bioinformatics 19, 524–531 (2003)

    Article  CAS  Google Scholar 

  20. Fujarewicz, K., Kimmel, M., Lipniacki, T., Świerniak, A.: Parameter estimation for models of cell signaling pathways based on semi-quantitative data. In: BioMed 2006: Proceedings of the 24th IASTED international conference on Biomedical engineering, Anaheim, CA, USA, pp. 306–310. ACTA Press (2006)

    Google Scholar 

  21. Calzone, L., Chabrier-Rivier, N., Fages, F., Soliman, S.: Machine Learning Biochemical Networks from Temporal Logic Properties. In: Priami, C., Plotkin, G. (eds.) Transactions on Computational Systems Biology VI. LNCS (LNBI), vol. 4220, pp. 68–94. Springer, Heidelberg (2006)

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Donaldson, R., Gilbert, D. (2008). A Model Checking Approach to the Parameter Estimation of Biochemical Pathways. In: Heiner, M., Uhrmacher, A.M. (eds) Computational Methods in Systems Biology. CMSB 2008. Lecture Notes in Computer Science(), vol 5307. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88562-7_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-88562-7_20

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-88561-0

  • Online ISBN: 978-3-540-88562-7

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics