Skip to main content

Modeling Cellular Behavior with Hybrid Automata: Bisimulation and Collapsing

  • Conference paper
  • First Online:

Part of the book series: Lecture Notes in Computer Science ((LNCS,volume 2602))

Abstract

Many biological systems can be modeled using systems of ordinary differential algebraic equations (e.g.,S-systems),thus allowing the study of their solutions and behavior automatically with suitable software tools (e.g.,PLAS, Octave/Matlab tm ).Usually,numerical solutions (traces or trajectories) for appropriate initial conditions are analyzed in order to infer significant properties of the biological systems under study. When several variables are involved and the traces span over a long interval of time,the analysis phase necessitates automation in a scalable and efficient manner. Earlier,we have advocated and experimented with the use of automata and temporal logics for this purpose (XS-systems and Simpathica) and here we continue our investigation more deeply.

We propose the use of hybrid automata and we discuss the use of the notions of bisimulation and collapsing for a “qualitative” analysis of the temporal evolution of biological systems. As compared with our previous proposal,hybrid automata allow maintenance of more information about the differential equations (S-system)than standard automata.The use of the notion of bisimulation in the definition of the projection operation (restrictions to a subset of “interesting”variables)makes possible to work with reduced automata satisfying the same formulae as the initial ones. Finally,the notion of collapsing is introduced to move toward still simpler and equivalent automata taming the complexity of the automata whose number of states depends on the level of approximation allowed.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. R. Alur, C. Belta, F. Ivancic, V. Kumar, M. Mintz, G.J. Pappas, H. Rubin, and J. Schug. Hybrid modeling and simulation of biomolecular networks.In Hybrid Systems: Computation and Control, volume 2034 of LNCS pages 19–22. Springer-Verlag, 2001.60, 62, 67

    Chapter  Google Scholar 

  2. R. Alur, C. Courcoubetis, T.A. Henzinger, and P.H. Ho.Hybrid automata:An algorithmic approach to the specification and verification of hybrid systems.In R.L. Grossman, A. Nerode, A.P. Ravn, and H. Richel,editors, Hybrid Systems LNCS, pages 209–229. Springer-Verlag, 1992. 66

    Google Scholar 

  3. M. Antoniotti, F.C. Park, A. Policriti, N. Ugel, and B. Mishra. Foundations of a Query and Simulation System for the odeling of Biochemical and Biological Processes. In Proc. of the Pacific Symposium of Biocomputing (PSB’03) 2003. 58, 59

    Google Scholar 

  4. M. Antoniotti, A. Policriti, N. Ugel, and B. Mishra. XS-systems:extended S-systems and algebraic differential automata for modeling cellular behaviour.In Proc. of Int. Conference on High Performance Computing (HiPC’02) 2002. 58, 59, 60, 63, 64, 66, 71

    Google Scholar 

  5. M. Antoniotti, A. Policriti, N. Ugel, and B. Mishra. Model Building and Model Checking for Biological Processes.Cell Biochemistry and Biophysics 2003. To appear. 58

    Google Scholar 

  6. U.S. Bhalla. Data Base of Quatitative Cellular Signaling (DOQCS).Website at http://doqcs.ncbs.res.in/, 2001.58

  7. R.W. Brockett. Dynamical systems and their associated automata. In Systems and Networks: Mathematical Theory and Applications, volume 77. Akademie-Verlag, Berlin, 1994. 59

    Google Scholar 

  8. E.M. Clarke, O. Grumberg, and D.A. Peled. Model checking IT Press, 1999. 63

    Google Scholar 

  9. E.M. Clarke and E.A. Emerson. Design and synthesis of synchronization skeletons using brancing time temporal logic. In Proc. Workshop Logic of Programs volume 131 of LNCS Springer, 1981. 68

    Google Scholar 

  10. M. Curti, P. Degano, C. Priami, and C.T. Baldari. Casualπ-calculus for biochemical modelling. DIT 02, University of Trento, 2002. 60

    Google Scholar 

  11. H. de Jong. Modeling and simulation of genetic regulatory systems:A literature review. DIT 4032, Inria, 2000.59

    Google Scholar 

  12. A. Dovier, C. Piazza, and A. Policriti. A fast bisimulation algorithm. In G. Berry, H. Comon, and A. Finkel, editors, Proc. of Int. Conference on Computer Aided Verification (CAV’01) volume 2102 of LNCS pages 79–90. Springer-Verlag, 2001. 70

    Google Scholar 

  13. M. Elowitz and S. Leibler. A synthetic oscillatory network of transcriptional regulators. Nature 403:335–338, 2000. 59, 65

    Article  Google Scholar 

  14. E.A. Emerson. Temporal and modal logic. In J. van Leeuwen, editor, Handbook of Theoretical Computer Science volume B, pages 995–1072. MIT Press, 1990. 62, 64

    Google Scholar 

  15. T.A. Henzinger. The theory of hybrid automata. In Proc. of IEEE Symposium on Logic in Computer Science (LICS’96) pages 278–292. IEEE Press, 1996. 67, 68

    Google Scholar 

  16. T.A. Henzinger, P.H. Ho, and H. Wong-Toi. HYTECH:A model checker for hybrid systems. International Journal on Software Tools for Technology Transfer 1(1–2):110–122, 1997. 67

    Article  MATH  Google Scholar 

  17. J.E. Hopcroft and J.D. Ullman. Introduction to Automata Theory, Languages, and Computation Addison-Wesley, 1979.63

    Google Scholar 

  18. P.D. Karp, M. Riley, S. Paley, and A. Pellegrini-Toole. The etaCyc Database. Nucleic Acid Research 30(1):59, 2002.58

    Article  Google Scholar 

  19. P.D. Karp, M. Riley, M. Saier, and S. Paley A. Pellegrini-Toole.The EcoCyc Database. Nucleic Acids Research 30(1):56, 2002.58

    Article  Google Scholar 

  20. H. Kitano.Systems Biology:an Overview. Science 295:1662–1664, March 2002. 57

    Google Scholar 

  21. O. Müller and T. Stauner. Modelling and verification using linear hybrid automata. Mathematical and Computer Modelling of Dynamical Systems 6(1):71–89, 2000. 67

    Article  MATH  Google Scholar 

  22. R. Paige, R.E. Tarjan, and R. Bonic. A linear time solution to the single function coarsest partition problem. Theoretical Computer Science 40:67–84, 1985.70

    Article  MATH  MathSciNet  Google Scholar 

  23. A. Regev, W. Silverman, and E. Shapiro. Representation and simulation of biochemical processes using the π-calculus process algebra. In Proc. of thePacific Symposium of Biocomputing (PSB’01) pages 459-70, 2003. 60

    Google Scholar 

  24. D. Shasha, A. Kouranov, L. Lejay, C. Chou, and G. Coruzzi. Combinatorial Design to study regulation by multiple input signals:A tool for parsimony in the post-genomics era. Plant Physiology 127:1590–1594, December 2001.59

    Google Scholar 

  25. E.O. Voit. Computational Analysis of Biochemical Systems. A Pratical Guide for Biochemists and Molecular Biologists Cambridge University Press, 2000. 60, 61, 65

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Antoniotti, M., Mishra, B., Piazza, C., Policriti, A., Simeoni, M. (2003). Modeling Cellular Behavior with Hybrid Automata: Bisimulation and Collapsing. In: Priami, C. (eds) Computational Methods in Systems Biology. CMSB 2003. Lecture Notes in Computer Science, vol 2602. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-36481-1_6

Download citation

  • DOI: https://doi.org/10.1007/3-540-36481-1_6

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-00605-3

  • Online ISBN: 978-3-540-36481-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics