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Parallelized Parameter Estimation of Biological Pathway Models

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Hybrid Systems Biology (HSB 2015)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 9271))

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Abstract

We develop a GPU based technique to analyze bio-pathway models consisting of systems of ordinary differential equations (ODEs). A key component in our technique is an online procedure for verifying whether a numerically generated trajectory of a model satisfies a property expressed in bounded linear temporal logic. Using this procedure, we construct a statistical model checking algorithm which exploits the massive parallelism offered by GPUs while respecting the severe constraints imposed by their memory hierarchy and the hardware execution model. To demonstrate the computational power of our method, we use it to solve the parameter estimation problem for bio-pathway models. With three realistic benchmarks, we show that the proposed technique is computationally efficient and scales well with the number of GPU units deployed. Since both the verification framework and the computational platform are generic, our scheme can be used to solve a variety of analysis problems for models consisting of large systems of ODEs.

This research was supported by the Singapore MOE grant MOE2013-T2-2-033.

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Notes

  1. 1.

    Source code available at https://www.comp.nus.edu.sg/~rpsysbio/smcgpu/.

References

  1. Barnat, J., Brim, L., Cerná, I., Drazan, S., Fabriková, J., Láník, J., Safránek, D., Ma, H.: Biodivine: A framework for parallel analysis of biological models. In: Proceedings Second International Workshop on Computational Models for Cell Processes, COMPMOD 2009, Eindhoven, The Netherlands, 3 November 2009, pp. 31–45 (2009)

    Google Scholar 

  2. Barnat, J., Brim, L., Ceska, M., Lamr, T.: Cuda accelerated LTL model checking. In: 2009 15th International Conference on Parallel and Distributed Systems (ICPADS), pp. 34–41. IEEE (2009)

    Google Scholar 

  3. Barre, B., Klein, M., Soucy-Boivin, M., Ollivier, P.-A., Hallé, S.: MapReduce for parallel trace validation of LTL properties. In: Qadeer, S., Tasiran, S. (eds.) RV 2012. LNCS, vol. 7687, pp. 184–198. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  4. Biere, A., Cimatti, A., Clarke, E., Zhu, Y.: Symbolic model checking without BDDs. In: Cleaveland, W.R. (ed.) TACAS 1999. LNCS, vol. 1579, p. 193. Springer, Heidelberg (1999)

    Chapter  Google Scholar 

  5. Bortolussi, L., Sanguinetti, G.: Learning and designing stochastic processes from logical constraints. In: Joshi, K., Siegle, M., Stoelinga, M., D’Argenio, P.R. (eds.) QEST 2013. LNCS, vol. 8054, pp. 89–105. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  6. Brown, K.S., Hill, C.C., Calero, G.A., Myers, C.R., Lee, K.H., Sethna, J.P., Cerione, R.A.: The statistical mechanics of complex signaling networks: nerve growth factor signaling. Phys. Biol. 1(3), 184 (2004)

    Article  Google Scholar 

  7. Bulychev, P., David, A., Larsen, K.G., Mikučionis, M., Poulsen, D.B., Legay, A., Wang, Z.: Uppaal-smc: Statistical model checking for priced timed automata. arXiv preprint arXiv:1207.1272 (2012)

  8. Clarke, E.M., Faeder, J.R., Langmead, C.J., Harris, L.A., Jha, S.K., Legay, A.: Statistical model checking in BioLab: applications to the automated analysis of T-cell receptor signaling pathway. In: Heiner, M., Uhrmacher, A.M. (eds.) CMSB 2008. LNCS (LNBI), vol. 5307, pp. 231–250. Springer, Heidelberg (2008)

    Chapter  Google Scholar 

  9. David, A., Du, D., Guldstrand Larsen, K., Legay, A., Mikučionis, M.: Optimizing control strategy using statistical model checking. In: Brat, G., Rungta, N., Venet, A. (eds.) NFM 2013. LNCS, vol. 7871, pp. 352–367. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  10. Dean, J., Ghemawat, S.: MapReduce: simplified data processing on large clusters. Commun. ACM 51(1), 107–113 (2008)

    Article  Google Scholar 

  11. Goldbeter, A., Pourquié, O.: Modeling the segmentation clock as a network of coupled oscillations in the Notch, Wnt and FGF signaling pathways. J. Theoret. Biol. 252(3), 574–585 (2008)

    Article  MathSciNet  Google Scholar 

  12. Gyori, B.M., Liu, B., Paul, S., Ramanathan, R., Thiagarajan, P.: Approximate probabilistic verification of hybrid systems. In: Abate, A., Sǎfránek, D. (eds.) HSB 2015. LNCS (LNBI), vol. 9271, pp. 96–116. Springer, Heidelberg (2015)

    Google Scholar 

  13. Hagiescu, A., Liu, B., Ramanathan, R., Palaniappan, S.K., Cui, Z., Chattopadhyay, B., Thiagarajan, P., Wong, W.F.: GPU code generation for ode-based applications with phased shared-data access patterns. ACM Trans. Archit. Code Optim. (TACO) 10(4), 55 (2013)

    Google Scholar 

  14. Hindmarsh, A., Brown, P., Grant, K., Lee, S., Serban, R., Shumaker, D., Woodward, C.: SUNDIALS: Suite of nonlinear and differential/algebraic equation solvers. ACM T. Math. Softw. 31(3), 363–396 (2005)

    Article  MathSciNet  MATH  Google Scholar 

  15. Hirsch, M., Smale, S., Devaney, R.: Differential equations, dynamical systems, and an introduction to chaos. Academic Press, New York (2012)

    MATH  Google Scholar 

  16. Jha, S.K., Langmead, C.J.: Synthesis and infeasibility analysis for stochastic models of biochemical systems using statistical model checking and abstraction refinement. Theoret. Comput. Sci. 412(21), 2162–2187 (2011)

    Article  MathSciNet  MATH  Google Scholar 

  17. Klipp, E., Herwig, R., Kowald, A., Wierling, C., Lehrach, H.: Systems Biology in Practice: Concepts, Implementation and Application. Wiley-VCH, Weinheim (2005)

    Book  Google Scholar 

  18. Kuhtz, L., Finkbeiner, B.: Efficient parallel path checking for linear-time temporal logic with past and bounds. arXiv preprint arXiv:1210.0574 (2012)

  19. Lambert, J.D.: Numerical Methods for Ordinary Differential Systems: The Initial Value Problem. Wiley, Chichester (1991)

    MATH  Google Scholar 

  20. Le Novere, N., Bornstein, B., Broicher, A., Courtot, M., Donizelli, M., Dharuri, H., Li, L., Sauro, H., Schilstra, M., Shapiro, B., Snoep, J., Hucka, M.: BioModels database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucleic Acids Res. 34, D689–D691 (2006)

    Article  Google Scholar 

  21. Legay, A., Delahaye, B., Bensalem, S.: Statistical model checking: an overview. In: Barringer, H., et al. (eds.) RV 2010. LNCS, vol. 6418, pp. 122–135. Springer, Heidelberg (2010)

    Chapter  Google Scholar 

  22. Lindholm, E., Nickolls, J., Oberman, S., Montrym, J.: Nvidia tesla: a unified graphics and computing architecture. IEEE Micro 28(2), 39–55 (2008)

    Article  Google Scholar 

  23. Liu, B., Hagiescu, A., Palaniappan, S.K., Chattopadhyay, B., Cui, Z., Wong, W.F., Thiagarajan, P.: Approximate probabilistic analysis of biopathway dynamics. Bioinformatics 28(11), 1508–1516 (2012)

    Article  Google Scholar 

  24. Maeda, A., Ozaki, Y.I., Sivakumaran, S., Akiyama, T., Urakubo, H., Usami, A., Sato, M., Kaibuchi, K., Kuroda, S.: Ca2+-independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response. Genes to Cells 11(9), 1071–1083 (2006)

    Article  Google Scholar 

  25. Maedo, A., Ozaki, Y., Sivakumaran, S., Akiyama, T., Urakubo, H., Usami, A., Sato, M., Kaibuchi, K., Kuroda, S.: Ca\(^{2+}\)-independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response. Genes Cells 11, 1071–1083 (2006)

    Article  Google Scholar 

  26. Moles, C.G., Mendes, P., Banga, J.R.: Parameter estimation in biochemical pathways: a comparison of global optimization methods. Genome Res. 13(11), 2467–2474 (2003)

    Article  Google Scholar 

  27. Murray, L.: GPU acceleration of Runge-Kutta integrators. IEEE Trans. Parallel Distrib. Syst. 23(1), 94–101 (2012)

    Article  Google Scholar 

  28. Oshima, K., Matsumoto, T., Fujita, M.: Hardware implementation of BLTL property checkers for acceleration of statistical model checking. In: Proceedings of the International Conference on Computer-Aided Design, pp. 670–676. IEEE Press (2013)

    Google Scholar 

  29. Palaniappan, S.K., Gyori, B.M., Liu, B., Hsu, D., Thiagarajan, P.S.: Statistical model checking based calibration and analysis of bio-pathway models. In: Gupta, A., Henzinger, T.A. (eds.) CMSB 2013. LNCS, vol. 8130, pp. 120–134. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  30. Runarsson, T.P., Yao, X.: Stochastic ranking for constrained evolutionary optimization. IEEE Trans. Evol. Comput. 4(3), 284–294 (2000)

    Article  Google Scholar 

  31. Sen, K., Viswanathan, M., Agha, G.: On statistical model checking of stochastic systems. In: Etessami, K., Rajamani, S.K. (eds.) CAV 2005. LNCS, vol. 3576, pp. 266–280. Springer, Heidelberg (2005)

    Chapter  Google Scholar 

  32. Wald, A.: Sequential tests of statistical hypotheses. Ann. Math. Stat. 16, 117–186 (1945)

    Article  MathSciNet  MATH  Google Scholar 

  33. Younes, H.L., Kwiatkowska, M., Norman, G., Parker, D.: Numerical vs. statistical probabilistic model checking. Int. J. Softw. Tools Technol. Transfer 8(3), 216–228 (2006)

    Article  MATH  Google Scholar 

  34. Younes, H.L., Simmons, R.G.: Statistical probabilistic model checking with a focus on time-bounded properties. Inf. Comput. 204(9), 1368–1409 (2006)

    Article  MathSciNet  MATH  Google Scholar 

  35. Zhou, Y., Liepe, J., Sheng, X., Stumpf, M.P., Barnes, C.: GPU accelerated biochemical network simulation. Bioinformatics 27(6), 874–876 (2011)

    Article  Google Scholar 

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Correspondence to R. Ramanathan .

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Ramanathan, R., Zhang, Y., Zhou, J., Gyori, B.M., Wong, WF., Thiagarajan, P.S. (2015). Parallelized Parameter Estimation of Biological Pathway Models. In: Abate, A., Šafránek, D. (eds) Hybrid Systems Biology. HSB 2015. Lecture Notes in Computer Science(), vol 9271. Springer, Cham. https://doi.org/10.1007/978-3-319-26916-0_3

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  • DOI: https://doi.org/10.1007/978-3-319-26916-0_3

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