Advertisement

Qualitative Petri Net Modelling of Genetic Networks

  • Claudine Chaouiya
  • Elisabeth Remy
  • Denis Thieffry
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4220)

Abstract

The complexity of biological regulatory networks calls for the development of proper mathematical methods to model their structures and to give insight in their dynamical behaviours. One qualitative approach consists in modelling regulatory networks in terms of logical equations (using either Boolean or multi-level discretisation). Petri Nets (PNs) offer a complementary framework to analyse large systems.

In this paper, we propose to articulate the logical approach with PNs. We first revisit the definition of a rigourous and systematic mapping of multi-level logical regulatory models into specific standard PNs, called Multi-level Regulatory Petri Nets (MRPNs). In particular, we consider the case of multiple arcs representing different regulatory effects from the same source. We further propose a mapping of multi-level logical regulatory models into Coloured PNs, called Coloured Regulatory Petri Nets (CRPNs). These CRPNs provide an intuitive graphical representation of regulatory networks, relatively easy to grasp.

Finally, we present the PN translation and the analysis of a multi-level logical model of the core regulatory network controlling the differentiation of T-helper lymphocytes into Th1 and Th2 types.

Keywords

Regulatory Network Genetic Network Logical Parameter Regulatory Graph State Transition Graph 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bryant, R.: Graph-Based Algorithms for Boolean Function Manipulation. IEEE Transactions on Computers C-35, 677–691 (1986)CrossRefGoogle Scholar
  2. 2.
    Chaouiya, C., Remy, E., Mossé, B., Thieffry, D.: Qualitative analysis of regulatory graphs: A computational tool based on a discrete formal framework. LNCIS, vol. 294, pp. 119–126 (2003)Google Scholar
  3. 3.
    Chaouiya, C., Remy, É., Ruet, P., Thieffry, D.: Qualitative Modelling of Genetic Networks: From Logical Regulatory Graphs to Standard Petri Nets. In: Cortadella, J., Reisig, W. (eds.) ICATPN 2004. LNCS, vol. 3099, pp. 137–156. Springer, Heidelberg (2004)CrossRefGoogle Scholar
  4. 4.
    Chaouiya, C., Remy, E., Thieffry, D.: Petri Net Modelling of Biological Regulatory Networks. In: Proc. of CompBioNets 2004. KCL publications, London (2004)Google Scholar
  5. 5.
    Comet, J.-P., Klaudel, H., Liauzu, S.: Modeling Multi-valued Genetic Regulatory Networks Using High-Level Petri Nets. In: Ciardo, G., Darondeau, P. (eds.) ICATPN 2005. LNCS, vol. 3536, pp. 208–227. Springer, Heidelberg (2005)CrossRefGoogle Scholar
  6. 6.
    de Jong, H.: Modeling and Simulation of Genetic Regulatory Systems: A Literature Review. J. Comput. Biol. 9, 67–103 (2002)CrossRefGoogle Scholar
  7. 7.
    Devloo, V., Hansen, P., Labbe, M.: Identification of all steady states in large networks by logical analysis. Bull. Math. Biol. 65, 1025–1051 (2003)CrossRefGoogle Scholar
  8. 8.
    Glass, L., Kauffman, S.A.: The logical analysis of continuous, non-linear biochemical control networks. J. theor. Biol. 39, 103–129 (1973)CrossRefGoogle Scholar
  9. 9.
    Gonzalez, A.G., Naldi, A., Sánchez, L., Thieffry, D., Chaouiya, C.: GINsim: a software suite for the qualitative modelling, simulation and analysis of regulatory networks. Biosystems 84(2), 91–100 (2006)CrossRefGoogle Scholar
  10. 10.
    Goss, P.J.E., Peccoud, J.: Quantitative modeling of stochastic systems in molecular biology by using stochastic Petri nets. Proc. Nat. Acad. Sci. USA. 95, 6750–6755 (1998)CrossRefGoogle Scholar
  11. 11.
    Hardy, S., Robillard, P.N.: Modeling and simulation of molecular biology systems using petri nets: modeling goals of various approaches. J. Bioinform. Comput. Biol. 2, 595–613 (2004)CrossRefGoogle Scholar
  12. 12.
    Heiner, M., Koch, I.: Petri Net Based Model Validation in Systems Biology. In: Cortadella, J., Reisig, W. (eds.) ICATPN 2004. LNCS, vol. 3099, pp. 216–237. Springer, Heidelberg (2004)CrossRefGoogle Scholar
  13. 13.
    Hofestädt, R., Thelen, S.: Quantitative Modeling of Biochemical Networks. Silico Biol. 1, 39–53 (1998)Google Scholar
  14. 14.
    Jensen, K.: An introduction to the theoretical aspects of coloured Petri nets. In: de Bakker, J.W., de Roever, W.-P., Rozenberg, G. (eds.) REX 1993. LNCS, vol. 803, pp. 230–272. Springer, Heidelberg (1994)Google Scholar
  15. 15.
    Matsuno, H., Doi, A., Nagasaki, M., Miyano, S.: Hybrid Petri net representation of gene regulatory networks. In: Proc. Pac. Symp. Biocomput., pp. 341–352 (2000)Google Scholar
  16. 16.
    Mendoza, L.: A network model for the control of the differentiation process in Th cells. Biosystems 84(2), 101–114 (2006)CrossRefGoogle Scholar
  17. 17.
    Murata, T.: Petri Nets: Properties, Analysis and Applications. Proc. IEEE 77, 541–580 (1989)CrossRefGoogle Scholar
  18. 18.
    Reddy, V.N., Liebman, M.N., Mavrovouniotis, M.L.: Qualitative analysis of biochemical reaction systems. Comput. Biol. Med. 26, 9–24 (1996)CrossRefGoogle Scholar
  19. 19.
    Remy, É., Ruet, P., Mendoza, L., Thieffry, D., Chaouiya, C.: From logical regulatory graphs to standard petri nets: Dynamical roles and functionality of feedback circuits. In: Priami, C., Ingólfsdóttir, A., Mishra, B., Riis Nielson, H. (eds.) Transactions on Computational Systems Biology VII. LNCS (LNBI), vol. 4230, pp. 56–72. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  20. 20.
    Simao, E., Remy, E., Thieffry, D., Chaouiya, C.: Qualitative Modelling of Regulated Metabolic Pathways: Application to the Tryptophan Biosynthesis in E. Coli. Bioinformatics 21, 190–196 (2005)CrossRefGoogle Scholar
  21. 21.
    Thomas, R.: Regulatory networks seen as asynchronous automata: a logical description. J. theor. Biol. 153, 1–23 (1991)CrossRefGoogle Scholar
  22. 22.
    Thomas, R., Thieffry, D., Kaufman, M.: Dynamical behaviour of biological regulatory networks–I. Biological role of feedback loops and practical use of the concept of the loop-characteristic state. Bull. Math. Biol. 57, 247–276 (1995)zbMATHGoogle Scholar
  23. 23.
    Zevedei-Oancea, I., Schuster, S.: Topological analysis of metabolic networks based on Petri net theory. Silico Biol. 3, 0029 (2003)Google Scholar
  24. 24.
  25. 25.
    GINsim (Gene Interaction Network simulation), URL http://gin.univ-mrs.fr/GINsim

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Claudine Chaouiya
    • 1
  • Elisabeth Remy
    • 2
  • Denis Thieffry
    • 1
  1. 1.Institut de biologie du Développement de Marseille Luminy, UMR 6216MarseilleFrance
  2. 2.Institut de Mathématiques de Luminy, UMR 6206MarseilleFrance

Personalised recommendations