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Modeling Multi-valued Genetic Regulatory Networks Using High-Level Petri Nets

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Applications and Theory of Petri Nets 2005 (ICATPN 2005)

Part of the book series: Lecture Notes in Computer Science ((LNTCS,volume 3536))

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Abstract

Regulatory networks are at the core of all biological functions from bio-chemical pathways to gene regulation and cell communication processes. Because of the complexity of the interweaving retroactions, the overall behavior is difficult to grasp and the development of formal methods is needed in order to confront the supposed properties of the biological system to the model. We revisit here the tremendous work of R. Thomas and show that its binary and also its multi-valued approach can be expressed in a unified way with high-level Petri nets.

A compact modeling of genetic networks is proposed in which the tokens represent gene’s expression levels and their dynamical behavior depends on a certain number of biological parameters. This allows us to take advantage of techniques and tools in the field of high-level Petri nets. A developed prototype allows a biologist to verify systematically the coherence of the system under various hypotheses. These hypotheses are translated into temporal logic formulae and the model-checking techniques are used to retain only the models whose behavior is coherent with the biological knowledge.

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References

  1. Huang, S.: Genomics, complexity and drug discovery: insights from boolean network models of cellular regulation. Pharmacogenomics. 2, 203–222 (2001)

    Article  Google Scholar 

  2. Wolkenhauer, O.: Systems biology: the reincarnation of systems theory applied in biology? Brief Bioinform. 2, 258–270 (2001)

    Article  Google Scholar 

  3. Kitano, H.: Computational systems biology. Nature 420, 206–210 (2002)

    Article  Google Scholar 

  4. Hasty, J., McMillen, D., Collins, J.J.: Engineered gene circuits. Nature 420, 224–230 (2002)

    Article  Google Scholar 

  5. Kitano, H.: Looking beyond the details: a rise in system-oriented approaches in genetics and molecular biology. Curr. Genet. 41, 1–10 (2002)

    Article  Google Scholar 

  6. Thomas, R., Gathoye, A.M., Lambert, L.: A complex control circuit. regulation of immunity in temperate bacteriophages. Eur. J. Biochem. 71, 211–227 (1976)

    Article  Google Scholar 

  7. Thomas, R.: Logical analysis of systems comprising feedback loops. J. Theor. Biol. 73, 631–656 (1978)

    Article  Google Scholar 

  8. Snoussi, E.H.: Qualitative dynamics of a piecewise-linear differential equations: a discrete mapping approach. Dynamics and stability of Systems 4, 189–207 (1989)

    MATH  MathSciNet  Google Scholar 

  9. Kaufman, M., Thomas, R.: Model analysis of the bases of multistationarity in the humoral immune response. J. Theor. Biol. 129, 141–162 (1987)

    Article  Google Scholar 

  10. Snoussi, E., Thomas, R.: Logical identification of all steady states: the concept of feedback loop caracteristic states. Bull. Math. Biol. 55, 973–991 (1993)

    MATH  Google Scholar 

  11. Thomas, R., Kaufman, M.: Multistationarity, the basis of cell differentiation and memory. I & II. Chaos 11, 170–195 (2001)

    Article  MATH  MathSciNet  Google Scholar 

  12. Plathe, E., Mestl, T., Omholt, S.W.: Feedback loops, stability and multistationarity in dynamical systems. J. Biol. Syst. 3, 569–577 (1995)

    Article  Google Scholar 

  13. Snoussi, E.H.: Necessary conditions for multistationarity and stable periodicity. J. Biol. Syst. 6, 3–9 (1998)

    Article  MATH  Google Scholar 

  14. Cinquin, O., Demongeot, J.: Positive and negative feedback: striking a balance between necessary antagonists. J. Theor. Biol. 216, 229–241 (2002)

    Article  MathSciNet  Google Scholar 

  15. Soulé, C.: Graphical requirements for multistationarity. ComPlexUs 1, 123–133 (2003)

    Article  Google Scholar 

  16. Thomas, R., Thieffry, D., Kaufman, M.: Dynamical behaviour of biological regulatory networks - I. Bull. Math. Biol. 57, 247–276 (1995)

    MATH  Google Scholar 

  17. Pérès, S., Comet, J.P.: Contribution of computational tree logic to biological regulatory networks: example from pseudomonas aeruginosa. In: Priami, C. (ed.) CMSB 2003. LNCS, vol. 2602, pp. 47–56. Springer, Heidelberg (2003)

    Chapter  Google Scholar 

  18. Bernot, G., Comet, J.-P., Richard, A., Guespin, J.: Application of formal methods to biological regulatory networks: Extending Thomas’ asynchronous logical approach with temporal logic. J. Theor. Biol. 229, 339–347 (2004)

    Article  MathSciNet  Google Scholar 

  19. Guespin-Michel, J., Kaufman, M.: Positive feedback circuits and adaptive regulations in bacteria. Acta Biotheor. 49, 207–218 (2001)

    Article  Google Scholar 

  20. Chaouiya, C., Remy, E., 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)

    Chapter  Google Scholar 

  21. Thomas, R., Thieffry, D., Kaufman, M.: Dynamical behaviour of biological regulatory networks - I. biological role of feedback loops an practical use of the concept of the loop-characteristic state. Bull. Math. Biol. 57, 247–276 (1995)

    MATH  Google Scholar 

  22. Mäkelä, M.: Maria: Modular reachability analyser for algebraic system nets. In: Esparza, J., Lakos, C.A. (eds.) ICATPN 2002. LNCS, vol. 2360, pp. 434–444. Springer, Heidelberg (2002)

    Chapter  Google Scholar 

  23. Chaouiya, C., Remy, E., Mossé, B., Thieffry, D.: GINML: towards a GXL based format for logical regulatory networks and dynamical graphs (2003), http://www.esil.univ-evry.fr/~chaouiya/GINsim/ginml.html

  24. Bernot, G., Cassez, F., Comet, J.P., Delaplace, F., Müller, Roux, O.: Semantics of biological regulatory networks. In: Biology BioConcur 2003 (2003)

    Google Scholar 

  25. Pommereau, F.: Modèles composables et concurrents pour le temps-rèel. PhD thesis, Universitè Paris 12 (2002)

    Google Scholar 

  26. Klaudel, H., Pommereau, F.: Asynchronous links in the PBC and M-nets. In: Thiagarajan, P.S., Yap, R.H.C. (eds.) ASIAN 1999. LNCS, vol. 1742, pp. 190–200. Springer, Heidelberg (1999)

    Chapter  Google Scholar 

  27. Khomenko, V., Koutny, M., Vogler, W.: Canonical prefixes of petri net unfoldings. Acta Informatica 40, 95–118 (2003)

    Article  MATH  MathSciNet  Google Scholar 

  28. Grahlman, B.: The state of PEP. In: Haeberer, A.M. (ed.) AMAST 1998. LNCS, vol. 1548, pp. 522–526. Springer, Heidelberg (1998)

    Chapter  Google Scholar 

  29. Schmidt, K.: LoLA: a low level analyser. In: Nielsen, M., Simpson, D. (eds.) ICATPN 2000. LNCS, vol. 1825, pp. 465–474. Springer, Heidelberg (2000)

    Chapter  Google Scholar 

  30. Varpaaniemi, K., Halme, J., Hiekkanen, K., Pyssysalo, T.: Prod: reference manual. Technical Report B13, Helsinki University of Technology, Finland (1995)

    Google Scholar 

  31. Cimatti, A., Clarke, E., Giunchiglia, F., Roveri, M.: Nusmv: a reimplementation of smv. In: STTT 1998. BRICS Notes Series, NS-98-4, pp. 25–31 (1998)

    Google Scholar 

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Author information

Authors and Affiliations

  1. LaMI, UMR CNRS 8042, Université d’Evry-Val d’Essonne, Boulevard François Mitterrand, 91025, Evry Cedex, France

    Jean-Paul Comet, Hanna Klaudel & Stéphane Liauzu

Authors
  1. Jean-Paul Comet
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  2. Hanna Klaudel
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  3. Stéphane Liauzu
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Editor information

Editors and Affiliations

  1. UC Riverside,  

    Gianfranco Ciardo

  2. IRISA, CNRS & INRIA, Rennes, France

    Philippe Darondeau

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Comet, JP., Klaudel, H., Liauzu, S. (2005). Modeling Multi-valued Genetic Regulatory Networks Using High-Level Petri Nets. In: Ciardo, G., Darondeau, P. (eds) Applications and Theory of Petri Nets 2005. ICATPN 2005. Lecture Notes in Computer Science, vol 3536. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11494744_13

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  • DOI: https://doi.org/10.1007/11494744_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-26301-2

  • Online ISBN: 978-3-540-31559-9

  • eBook Packages: Computer ScienceComputer Science (R0)

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