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High-Performance Symbolic Parameter Synthesis of Biological Models: A Case Study

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Computational Methods in Systems Biology (CMSB 2016)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 9859))

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Abstract

Complex behaviour arising in biological systems is described by highly parameterised dynamical models. Most of the parameters are mutually dependent and therefore it is hard and computationally demanding to find admissible parameter values with respect to hypothesised constraints and wet-lab measurements. Recently, we have developed several high-performance techniques for parameter synthesis that are based on parallel coloured model checking. These methods allow to obtain parameter values that guarantee satisfaction of a given set of dynamical properties and parameter constraints. In this paper, we review the applicability of our techniques in the context of biological systems. In particular, we provide an extended analysis of a genetic switch controlling the regulation in mammalian cell cycle phase transition and a synthetic pathway for biodegradation of a toxic pollutant in E. coli.

This work has been supported by the Czech Science Foundation grant GA15-11089S.

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References

  1. Ballarini, P., Guido, R., Mazza, T., Prandi, D.: Taming the complexity of biological pathways through parallel computing. Brief. Bioinform. 10(3), 278–288 (2009)

    Article  Google Scholar 

  2. Barnat, J., et al.: On parameter synthesis by parallel model checking. IEEE/ACM Trans. Comput. Biol. Bioinform. 9(3), 693–705 (2012)

    Article  MathSciNet  Google Scholar 

  3. Barrett, C., Fontaine, P., Tinelli, C.: The SMT-LIB Standard: Version 2.5. Technical report, Department of Computer Science, The University of Iowa (2015)

    Google Scholar 

  4. Bartocci, E., Lió, P.: Computational modeling, formal analysis, and tools for systems biology. PLoS Comput. Biol. 12(1), 1–22 (2016)

    Article  Google Scholar 

  5. Batt, G., Belta, C., Weiss, R.: Model checking genetic regulatory networks with parameter uncertainty. In: Bemporad, A., Bicchi, A., Buttazzo, G. (eds.) HSCC 2007. LNCS, vol. 4416, pp. 61–75. Springer, Heidelberg (2007)

    Chapter  Google Scholar 

  6. Batt, G., Yordanov, B., Weiss, R., Belta, C.: Robustness analysis and tuning of synthetic gene networks. Bioinformatics 23(18), 2415–2422 (2007)

    Article  Google Scholar 

  7. Beneš, N., Brim, L., Demko, M., Pastva, S., Šafránek, D.: Parallel SMT-based parameter synthesis with application to piecewise multi-affine systems. In: ATVA 2016. LNCS. Springer (2016) (to appear)

    Google Scholar 

  8. Bogomolov, S., Schilling, C., Bartocci, E., Batt, G., Kong, H., Grosu, R.: Abstraction-based parameter synthesis for multiaffine systems. In: Piterman, N., et al. (eds.) HVC 2015. LNCS, vol. 9434, pp. 19–35. Springer, Heidelberg (2015)

    Chapter  Google Scholar 

  9. Brim, L., Češka, M., Demko, M., Pastva, S., Šafránek, D.: Parameter synthesis by parallel coloured CTL model checking. In: Roux, O., Bourdon, J. (eds.) CMSB 2015. LNCS, vol. 9308, pp. 251–263. Springer, Heidelberg (2015)

    Chapter  Google Scholar 

  10. Calzone, L., Fages, F., Soliman, S.: BIOCHAM: an environment for modeling biological systems and formalizing experimental knowledge. Bioinformatics 22(14), 1805–1807 (2006)

    Article  Google Scholar 

  11. Dang, T., Dreossi, T., Piazza, C.: Parameter synthesis through temporal logic specifications. In: Bjørner, N., de Boer, F. (eds.) FM 2015. LNCS, vol. 9109, pp. 213–230. Springer, Heidelberg (2015)

    Chapter  Google Scholar 

  12. Donzé, A., Fanchon, E., Gattepaille, L.M., Maler, O., Tracqui, P.: Robustness analysis and behavior discrimination in enzymatic reaction networks. PLoS ONE 6(9), e24246 (2011)

    Article  Google Scholar 

  13. Dvořák, P.: Engineering of the synthetic metabolic pathway for biodegradation of environmental pollutant. Ph.D. thesis, Masaryk University (2014)

    Google Scholar 

  14. Gao, S., Kong, S., Clarke, E.M.: dReal: an SMT solver for nonlinear theories over the reals. In: Bonacina, M.P. (ed.) CADE 2013. LNCS, vol. 7898, pp. 208–214. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  15. Grosu, R., Batt, G., Fenton, F.H., Glimm, J., Le Guernic, C., Smolka, S.A., Bartocci, E.: From cardiac cells to genetic regulatory networks. In: Gopalakrishnan, G., Qadeer, S. (eds.) CAV 2011. LNCS, vol. 6806, pp. 396–411. Springer, Heidelberg (2011)

    Chapter  Google Scholar 

  16. Kurumbang, N.P., et al.: Computer-assisted engineering of the synthetic pathway for biodegradation of a toxic persistent pollutant. ACS Synth. Biol. 3(3), 172–181 (2013)

    Article  Google Scholar 

  17. Li, Y., Albarghouthi, A., Kincaid, Z., Gurfinkel, A., Chechik, M.: Symbolic optimization with SMT solvers. In: POPL 2014, pp. 607–618. ACM (2014)

    Google Scholar 

  18. Madsen, C., Shmarov, F., Zuliani, P.: BioPSy: an SMT-based tool for guaranteed parameter set synthesis of biological models. In: Roux, O., Bourdon, J. (eds.) CMSB 2015. LNCS, vol. 9308, pp. 182–194. Springer, Heidelberg (2015)

    Chapter  Google Scholar 

  19. Raue, A., et al.: Comparison of approaches for parameter identifiability analysis of biological systems. Bioinformatics 30, 1440–1448 (2014)

    Article  Google Scholar 

  20. Rizk, A., Batt, G., Fages, F., Soliman, S.: A general computational method for robustness analysis with applications to synthetic gene networks. Bioinformatics 25(12), i169–i178 (2009)

    Article  Google Scholar 

  21. Swat, M., Kel, A., Herzel, H.: Bifurcation analysis of the regulatory modules of the mammalian G1/S transition. Bioinformatics 20(10), 1506–1511 (2004)

    Article  Google Scholar 

  22. Yordanov, B., Belta, C.: Parameter synthesis for piecewise affine systems from temporal logic specifications. In: Egerstedt, M., Mishra, B. (eds.) HSCC 2008. LNCS, vol. 4981, pp. 542–555. Springer, Heidelberg (2008)

    Chapter  Google Scholar 

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Correspondence to David Šafránek .

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Demko, M., Beneš, N., Brim, L., Pastva, S., Šafránek, D. (2016). High-Performance Symbolic Parameter Synthesis of Biological Models: A Case Study. In: Bartocci, E., Lio, P., Paoletti, N. (eds) Computational Methods in Systems Biology. CMSB 2016. Lecture Notes in Computer Science(), vol 9859. Springer, Cham. https://doi.org/10.1007/978-3-319-45177-0_6

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  • DOI: https://doi.org/10.1007/978-3-319-45177-0_6

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