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Model Checking Genetic Regulatory Networks with Parameter Uncertainty

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Hybrid Systems: Computation and Control (HSCC 2007)

Part of the book series: Lecture Notes in Computer Science ((LNTCS,volume 4416))

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Abstract

The lack of precise numerical information for the values of biological parameters severely limits the development and analysis of models of genetic regulatory networks. To deal with this problem, we propose a method for the analysis of genetic regulatory networks with parameter uncertainty. We consider models based on piecewise-multiaffine differential equations, dynamical properties expressed in temporal logic, and intervals for the values of uncertain parameters. The problem is then either to guarantee that the system satisfies the expected properties for every possible parameter value - the corresponding parameter set is then called valid - or to find valid subsets of a given parameter set. The proposed method uses discrete abstractions and model checking, and allows for efficient search of the parameter space. This approach has been implemented in a tool for robust verification of gene networks (RoVerGeNe) and applied to the tuning of a synthetic network build in E. coli.

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References

  1. Kitano, H.: Systems biology: A brief overview. Science 295(5560), 1662–1664 (2002)

    Article  Google Scholar 

  2. Andrianantoandro, E., et al.: Synthetic biology: New engineering rules for an emerging discipline. Mol. Syst. Biol. (2006)

    Google Scholar 

  3. Szallasi, Z., Stelling, J., Periwal, V. (eds.): System Modeling in Cellular Biology: From Concepts to Nuts and Bolts. MIT Press, Cambridge (2006)

    Google Scholar 

  4. de Jong, H., Ropers, D.: Qualitative approaches to the analysis of genetic regulatory networks. In: Szallasi, Z., Stelling, J., Periwal, V. (eds.) System Modeling in Cellular Biology: From Concepts to Nuts and Bolts, pp. 125–148. MIT Press, Cambridge (2006)

    Google Scholar 

  5. Belta, C., Habets, L.C.G.J.M.: Controlling a class of nonlinear systems on rectangles. IEEE Trans. Aut. Control 51(11), 1749–1759 (2006)

    Article  MathSciNet  Google Scholar 

  6. Alur, R., et al.: Discrete abstractions of hybrid systems. Proc. IEEE 88(7), 971–984 (2000)

    Article  Google Scholar 

  7. Clarke, E.M., Grumberg, O., Peled, D.A.: Model Checking. MIT Press, Cambridge (1999)

    Google Scholar 

  8. Batt, G., Belta, C.: Model checking genetic regulatory networks with applications to synthetic biology. CISE Tech. Rep. 2006-IR-0030, Boston University (2006)

    Google Scholar 

  9. de Jong, H., et al.: Qualitative simulation of genetic regulatory networks using piecewise-linear models. Bull. Math. Biol. 66(2), 301–340 (2004)

    Article  MathSciNet  Google Scholar 

  10. Abate, A., Tiwari, A.: Box invariance of hybrid and switched systems. In: Proc. ADHS’06 (2006)

    Google Scholar 

  11. Belta, C., Habets, L.C.G.J.M., Kumar, V.: Control of multi-affine systems on rectangles with applications to hybrid biomolecular networks. In: Proc. CDC’02 (2002)

    Google Scholar 

  12. Mestl, T., Plahte, E., Omholt, S.: A mathematical framework for describing and analysing gene regulatory networks. J. Theor. Biol. 176, 291–300 (1995)

    Article  Google Scholar 

  13. Glass, L., Kauffman, S.: The logical analysis of continuous non-linear biochemical control networks. J. Theor. Biol. 39(1), 103–129 (1973)

    Article  Google Scholar 

  14. Kloetzer, M., Belta, C.: Reachability analysis of multi-affine systems. In: Hespanha, J.P., Tiwari, A. (eds.) HSCC 2006. LNCS, vol. 3927, pp. 348–362. Springer, Heidelberg (2006)

    Chapter  Google Scholar 

  15. Alur, R., Dang, T., Ivancic, F.: Progress on reachability analysis of hybrid systems using predicate abstraction. In: Maler, O., Pnueli, A. (eds.) HSCC 2003. LNCS, vol. 2623, pp. 4–19. Springer, Heidelberg (2003)

    Chapter  Google Scholar 

  16. Koutsoukos, X., Antsaklis, P.J.: Safety and reachability of piecewise linear hybrid dynamical systems based on discrete abstractions. J. Discrete Event Dynamic Systems 13(3), 203–243 (2003)

    Article  MATH  MathSciNet  Google Scholar 

  17. Batt, G., et al.: Validation of qualitative models of genetic regulatory networks by model checking: Analysis of the nutritional stress response in E. coli. Bioinformatics 21(Suppl. 1), i19–i28 (2005)

    Article  Google Scholar 

  18. Batt, G., Belta, C., Weiss, R.: Model checking liveness properties of genetic regulatory networks. In: Grumberg, O., Huth, M. (eds.) TACAS 2007. LNCS, vol. 4424, Springer, Heidelberg (2007)

    Chapter  Google Scholar 

  19. Hooshangi, S., Thiberge, S., Weiss, R.: Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. Proc. Natl. Acad. Sci. USA 102(10), 3581–3586 (2005)

    Article  Google Scholar 

  20. Annichini, A., Asarin, E., Bouajjani, A.: Symbolic techniques for parametric reasoning about counter and clock systems. In: Emerson, E.A., Sistla, A.P. (eds.) CAV 2000. LNCS, vol. 1855, pp. 419–434. Springer, Heidelberg (2000)

    Chapter  Google Scholar 

  21. Wang, F.: Symbolic parametric safety analysis of linear hybrid systems with BDD-like data-structures. IEEE Trans. Softw. Eng. 31(1), 38–51 (2005)

    Article  Google Scholar 

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

    Article  MATH  Google Scholar 

  23. Ghosh, R., Tomlin, C.J.: Symbolic reachable set computation of piecewise affine hybrid automata and its application to biological modelling: Delta-Notch protein signalling. IEE Proc. Syst. Biol. 1(1), 170–183 (2004)

    Google Scholar 

  24. Lin, H., Antsaklis, P.J.: Robust regulation of polytopic uncertain linear hybrid systems with networked control system applications. In: Antsaklis, P., Liu, D. (eds.) Stability and Control of Dynamical Systems Applications, Birkhäuser, Basel (2003)

    Google Scholar 

  25. Antoniotti, M., et al.: Taming the complexity of biochemical models through bisimulation and collapsing: Theory and practice. Theor. Comput. Sci. 325(1), 45–67 (2004)

    Article  MATH  MathSciNet  Google Scholar 

  26. Calzone, L., et al.: 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 

  27. Bernot, G., et al.: Application of formal methods to biological regulatory networks: Extending Thomas’ asynchronous logical approach with temporal logic. J. Theor. Biol. 229(3), 339–347 (2004)

    Article  MathSciNet  Google Scholar 

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Alberto Bemporad Antonio Bicchi Giorgio Buttazzo

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Batt, G., Belta, C., Weiss, R. (2007). Model Checking Genetic Regulatory Networks with Parameter Uncertainty. In: Bemporad, A., Bicchi, A., Buttazzo, G. (eds) Hybrid Systems: Computation and Control. HSCC 2007. Lecture Notes in Computer Science, vol 4416. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71493-4_8

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  • DOI: https://doi.org/10.1007/978-3-540-71493-4_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-71492-7

  • Online ISBN: 978-3-540-71493-4

  • eBook Packages: Computer ScienceComputer Science (R0)

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