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On Robustness Computation and Optimization in BIOCHAM-4

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Computational Methods in Systems Biology (CMSB 2018)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 11095))

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Abstract

BIOCHAM-4 is a tool for modeling, analyzing and synthesizing biochemical reaction networks with respect to some formal, yet possibly imprecise, specification of their behavior. We focus here on one new capability of this tool to optimize the robustness of a parametric model with respect to a specification of its dynamics in quantitative temporal logic. More precisely, we present two complementary notions of robustness: the statistical notion of model robustness to parameter perturbations, defined as its mean functionality, and a metric notion of formula satisfaction robustness, defined as the penetration depth in the validity domain of the temporal logic constraints. We show how the formula robustness can be used in BIOCHAM-4 with no extra cost as an objective function in the parameter optimization procedure, to actually improve the model robustness. We illustrate these unique features with a classical example of the hybrid systems community and provide some performance figures on a model of MAPK signalling with 37 parameters.

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Notes

  1. 1.

    http://lifeware.inria.fr/biocham4.

  2. 2.

    https://lifeware.inria.fr/wiki/Main/Software#CMSB18.

  3. 3.

    http://www.bugseng.com/ppl.

References

  1. Courbet, A., Amar, P., Fages, F., Renard, E., Molina, F.: Computer-aided biochemical programming of synthetic microreactors as diagnostic devices. Mol. Syst. Biol. 14(4), e7845 (2018)

    Article  Google Scholar 

  2. Donzé, A., Maler, O.: Robust satisfaction of temporal logic over real-valued signals. In: Chatterjee, K., Henzinger, T.A. (eds.) FORMATS 2010. LNCS, vol. 6246, pp. 92–106. Springer, Heidelberg (2010). https://doi.org/10.1007/978-3-642-15297-9_9

    Chapter  MATH  Google Scholar 

  3. Fages, F., Gay, S., Soliman, S.: Inferring reaction systems from ordinary differential equations. Theor. Comput. Sci. 599, 64–78 (2015)

    Article  MathSciNet  Google Scholar 

  4. Fages, F., Martinez, T., Rosenblueth, D., Soliman, S.: Influence networks compared with reaction networks: semantics, expressivity and attractors. IEEE/ACM Trans. Comput. Biol. Bioinform. (2018). https://doi.org/10.1109/TCBB.2018.2805686

  5. Fages, F., Rizk, A.: On temporal logic constraint solving for the analysis of numerical data time series. Theor. Comput. Sci. 408(1), 55–65 (2008)

    Article  Google Scholar 

  6. Fages, F., Traynard, P.: Temporal logic modeling of dynamical behaviors: first-order patterns and solvers. In: del Cerro, L.F., Inoue, K. (eds.) Logical Modeling of Biological Systems, Chap. 8, pp. 291–323. Wiley, Hoboken (2014)

    Google Scholar 

  7. Fainekos, G.E., Pappas, G.J.: Robustness of temporal logic specifications. In: Havelund, K., Núñez, M., Roşu, G., Wolff, B. (eds.) FATES/RV 2006. LNCS, vol. 4262, pp. 178–192. Springer, Heidelberg (2006). https://doi.org/10.1007/11940197_12

    Chapter  Google Scholar 

  8. Hansen, N., Ostermeier, A.: Completely derandomized self-adaptation in evolution strategies. Evol. Comput. 9(2), 159–195 (2001)

    Article  Google Scholar 

  9. Heitzler, D., et al.: Competing G protein-coupled receptor kinases balance G protein and \(\beta \)-arrestin signaling. Mol. Syst. Biol. 8, 590 (2012)

    Article  Google Scholar 

  10. Huang, C.Y., Ferrell, J.E.: Ultrasensitivity in the mitogen-activated protein kinase cascade. PNAS 93(19), 10078–10083 (1996)

    Article  Google Scholar 

  11. Kitano, H.: Towards a theory of biological robustness. Mol. Syst. Biol. 3, 137 (2007)

    Article  Google Scholar 

  12. Qiao, L., Nachbar, R.B., Kevrekidis, I.G., Shvartsman, S.Y.: Bistability and oscillations in the Huang-Ferrell model of MAPK signaling. PLoS Comput. Biol. 3(9), 1819–1826 (2007)

    Article  MathSciNet  Google Scholar 

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

    Article  Google Scholar 

  14. Rizk, A., Batt, G., Fages, F., Soliman, S.: Continuous valuations of temporal logic specifications with applications to parameter optimization and robustness measures. Theor. Comput. Sci. 412(26), 2827–2839 (2011)

    Article  MathSciNet  Google Scholar 

  15. Traynard, P., Fages, F., Soliman, S.: Trace simplifications preserving temporal logic formulae with case study in a coupled model of the cell cycle and the circadian clock. In: Mendes, P., Dada, J.O., Smallbone, K. (eds.) CMSB 2014. LNCS, vol. 8859, pp. 114–128. Springer, Cham (2014). https://doi.org/10.1007/978-3-319-12982-2_9

    Chapter  Google Scholar 

  16. Traynard, P., Feillet, C., Soliman, S., Delaunay, F., Fages, F.: Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: prediction of RevErb-\(\alpha \) up-regulation during mitosis. Biosystems 149, 59–69 (2016)

    Article  Google Scholar 

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Acknowledgment

This work benefited from partial support from the ANR project HYCLOCK contract DS0401.

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Correspondence to François Fages .

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Fages, F., Soliman, S. (2018). On Robustness Computation and Optimization in BIOCHAM-4. In: Češka, M., Šafránek, D. (eds) Computational Methods in Systems Biology. CMSB 2018. Lecture Notes in Computer Science(), vol 11095. Springer, Cham. https://doi.org/10.1007/978-3-319-99429-1_18

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  • DOI: https://doi.org/10.1007/978-3-319-99429-1_18

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-99428-4

  • Online ISBN: 978-3-319-99429-1

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