Skip to main content
Log in

Large Deviations for Gaussian Diffusions with Delay

  • Published:
Journal of Statistical Physics Aims and scope Submit manuscript

Abstract

Dynamical systems driven by nonlinear delay SDEs with small noise can exhibit important rare events on long timescales. When there is no delay, classical large deviations theory quantifies rare events such as escapes from metastable fixed points. Near such fixed points, one can approximate nonlinear delay SDEs by linear delay SDEs. Here, we develop a fully explicit large deviations framework for (necessarily Gaussian) processes \(X_t\) driven by linear delay SDEs with small diffusion coefficients. Our approach enables fast numerical computation of the action functional controlling rare events for \(X_t\) and of the most likely paths transiting from \(X_0 = p\) to \(X_T=q\). Via linear noise local approximations, we can then compute most likely routes of escape from metastable states for nonlinear delay SDEs. We apply our methodology to the detailed dynamics of a genetic regulatory circuit, namely the co-repressive toggle switch, which may be described by a nonlinear chemical Langevin SDE with delay.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Aurell, E., Sneppen, K.: Epigenetics as a first exit problem. Phys. Rev. Lett. 88, 048101 (2002)

    Article  ADS  Google Scholar 

  2. Azencott, R.: Grandes déviations et applications. In: Eighth Saint Flour Probability Summer School, Saint Flour,1978, vol. 774 of Lecture Notes in Mathematics, Springer, Berlin, pp. 1–176 (1980)

  3. Azencott, R., Freidlin, M.I., Varadhan, S.R.S.: Large Deviations at Saint-Flour. Probability at Saint-Flour. Springer, Heidelberg (2013)

    MATH  Google Scholar 

  4. Baker, C.T.H., Buckwar, E.: Numerical analysis of explicit one-step methods for stochastic delay differential equations. LMS J. Comput. Math. 3, 315–335 (2000). (electronic)

    Article  MathSciNet  MATH  Google Scholar 

  5. Balaban, N.Q., Merrin, J., Chait, R., Kowalik, L., Leibler, S.: Bacterial persistence as a phenotypic switch. Science 305, 1622–1625 (2004)

    Article  ADS  Google Scholar 

  6. Bao, J., Yuan, C.: Large deviations for neutral functional SDEs with jumps. Stochastics 87, 48–70 (2015)

    Article  MathSciNet  MATH  Google Scholar 

  7. Bellen, A., Zennaro, M.: Numerical Methods for Delay Differential Equations. Numerical Mathematics and Scientific Computation. The Clarendon Press and Oxford University Press, New York (2003)

    Book  MATH  Google Scholar 

  8. Bouchet, F., Laurie, J., Zaboronski, O.: Langevin dynamics, large deviations and instantons for the quasi-geostrophic model and two-dimensional Euler equations. J. Stat. Phys. 156, 1066–1092 (2014)

    Article  ADS  MathSciNet  MATH  Google Scholar 

  9. Bouchet, F., Grafke, T., Tangarife, T., Vanden-Eijnden, E.: Large deviations in fast-slow systems. J. Stat. Phys. 162, 793–812 (2016)

    Article  ADS  MathSciNet  MATH  Google Scholar 

  10. Brett, T., Galla, T.: Stochastic processes with distributed delays: chemical langevin equation and linear-noise approximation. Phys. Rev. Lett. 110, 250601 (2013)

    Article  ADS  Google Scholar 

  11. Çaǧatay, T., Turcotte, M., Elowitz, M., Garcia-Ojalvo, J., Süel, G.: Architecture-dependent noise discriminates functionally analogous differentiation circuits. Cell 139, 512–522 (2009)

    Article  Google Scholar 

  12. Chiarini, A., Fischer, M.: On large deviations for small noise Itô processes. Adv. Appl. Probab. 46, 1126–1147 (2014)

    Article  MathSciNet  MATH  Google Scholar 

  13. Davidson, C., Surette, M.: Individuality in bacteria. Annu. Rev. Genet. 42, 253–268 (2008)

    Article  Google Scholar 

  14. Dupin, E., Real, C., Glavieux-Pardanaud, C., Vaigot, P., Le Douarin, N.M.: Reversal of developmental restrictions in neural crest lineages: transition from schwann cells to glial-melanocytic precursors in vitro. Proc. Natl. Acad. Sci. 100, 5229–5233 (2003)

    Article  ADS  Google Scholar 

  15. Ren, W.E.W., Vanden-Eijnden, E.: Minimum action method for the study of rare events. Commun. Pure Appl. Math. 57, 637–656 (2004)

    Article  MathSciNet  MATH  Google Scholar 

  16. Eldar, A., Elowitz, M.: Functional roles for noise in genetic circuits. Nature 467, 167–173 (2010)

    Article  ADS  Google Scholar 

  17. Ferreira, J.C., Menegatto, V.A.: Eigenvalues of integral operators defined by smooth positive definite kernels. Integr. Eqn. Oper. Theory 64, 61–81 (2009)

    Article  MathSciNet  MATH  Google Scholar 

  18. Freidlin, M.I., Wentzell, A.D.: Random perturbations of dynamical systems, vol. 260 of Grundlehren der Mathematischen Wissenschaften [Fundamental Principles of Mathematical Sciences], 3rd edn, Springer, Heidelberg. Translated from the 1979 Russian original by Joseph Szücs (2012)

  19. Gadat, S., Panloup, F., Pellegrini, C.: Large deviation principle for invariant distributions of memory gradient diffusions. Electron. J. Probab. 18, 34–81 (2013)

    Article  MathSciNet  MATH  Google Scholar 

  20. Gardner, T.S., Cantor, C.R., Collins, J.J.: Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000)

    Article  ADS  Google Scholar 

  21. Guglielmi, N.: Delay dependent stability regions of $\Theta $-methods for delay differential equations. IMA J. Numer. Anal. 18, 399–418 (1998)

    Article  MathSciNet  MATH  Google Scholar 

  22. Gupta, C., López, J.M., Azencott, R., Bennett, M.R., Josić, K., Ott, W.: Modeling delay in genetic networks: from delay birth-death processes to delay stochastic differential equations. J. Chem. Phys. 140, 204108 (2014)

    Article  ADS  Google Scholar 

  23. He, E., Kapuy, O., Oliveira, R.A., Uhlmann, F., Tyson, J.J., Novák, B.: Systems-level feedbacks make the anaphase switch irreversible. Proc. Natl. Acad. Sci. USA 108, 10016–10021 (2011)

    Article  ADS  Google Scholar 

  24. Heymann, M., Vanden-Eijnden, E.: The geometric minimum action method: a least action principle on the space of curves. Commun. Pure Appl. Math. 61, 1052–1117 (2008)

    Article  MathSciNet  MATH  Google Scholar 

  25. Higham, D.J.: An algorithmic introduction to numerical simulation of stochastic differential equations. SIAM Rev. 43, 525–546 (2001). (electronic)

    Article  ADS  MathSciNet  MATH  Google Scholar 

  26. Hong, T., Xing, J., Li, L., Tyson, J.J.: A simple theoretical framework for understanding heterogeneous differentiation of cd4$^+$ t cells. BMC Syst. Biol. 6, 66 (2012)

    Article  Google Scholar 

  27. Kepler, T.B., Elston, T.C.: Stochasticity in transcriptional regulation: origins consequences, and mathematical representations. Biophys. J. 81, 3116–3136 (2001)

    Article  ADS  Google Scholar 

  28. Kushner, H.J.: Large deviations for two-time-scale diffusions, with delays. Appl. Math. Optim. 62, 295–322 (2010)

    Article  MathSciNet  MATH  Google Scholar 

  29. Li, T., Li, X., Zhou, X.: Finding transition pathways on manifolds. Multiscale Model. Simul. 14, 173–206 (2016)

    Article  MathSciNet  MATH  Google Scholar 

  30. Lindley, B.S., Schwartz, I.B.: An iterative action minimizing method for computing optimal paths in stochastic dynamical systems. Phys. D. 255, 22–30 (2013)

    Article  MathSciNet  MATH  Google Scholar 

  31. Luenberger, D.G.: Optimization by Vector Space Methods. Wiley, New York (1969)

    MATH  Google Scholar 

  32. Maamar, H., Dubnau, D.: Bistability in the bacillus subtilis k-state (competence) system requires a positive feedback loop. Mol. Microbiol. 56, 615–624 (2005)

    Article  Google Scholar 

  33. Maamar, H., Raj, A., Dubnau, D.: Noise in gene expression determines cell fate in bacillus subtilis. Science 317, 526–529 (2007)

    Article  ADS  Google Scholar 

  34. Mao, X.: Stochastic Differential Equations and Their Applications. Horwood Publishing Series in Mathematics & Applications. Horwood Publishing Limited, Chichester (1997)

    MATH  Google Scholar 

  35. Mao, X., Sabanis, S.: Numerical solutions of stochastic differential delay equations under local Lipschitz condition. J. Comput. Appl. Math. 151, 215–227 (2003)

    Article  ADS  MathSciNet  MATH  Google Scholar 

  36. Meeks, J.C., Campbell, E.L., Summers, M.L., Wong, F.C.: Cellular differentiation in the cyanobacterium nostoc punctiforme. Arch. Microbiol. 178, 395–403 (2002)

    Article  Google Scholar 

  37. Mo, C., Luo, J.: Large deviations for stochastic differential delay equations. Nonlinear Anal. 80, 202–210 (2013)

    Article  MathSciNet  MATH  Google Scholar 

  38. Mohammed, S.-E.A., Zhang, T.: Large deviations for stochastic systems with memory. Discret. Contin. Dyn. Syst. Ser. B 6, 881–893 (2006). (electronic)

    Article  MathSciNet  MATH  Google Scholar 

  39. Nevozhay, D., Adams, R.M., Van Itallie, E., Bennett, M.R., Balázsi, G.: Mapping the environmental fitness landscape of a synthetic gene circuit. PLoS Comput. Biol. 8, e1002480 (2012)

    Article  Google Scholar 

  40. Ozbudak, E.M., Thattai, M., Lim, H.N., Shraiman, B.I., van Oudenaarden, A.: Multistability in the lactose utilization network of Escherichia coli. Nature 427, 737–740 (2004)

    Article  ADS  Google Scholar 

  41. Puhalskii, A.A.: On some degenerate large deviation problems. Electron. J. Probab. 9(28), 862–886 (2004)

    Article  MathSciNet  MATH  Google Scholar 

  42. Süel, G., Kulkarni, R., Dworkin, J., Garcia-Ojalvo, J., Elowitz, M.: Tunability and noise dependence in differentiation dynamics. Science 315, 1716–1719 (2007)

    Article  ADS  Google Scholar 

  43. Süel, G.M., Garcia-Ojalvo, J., Liberman, L.M., Elowitz, M.B.: An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440, 545–550 (2006)

    Article  ADS  Google Scholar 

  44. Veliz-Cuba, A., Gupta, C., Bennett, M.R., Josić, K., Ott, W.: Effects of cell cycle noise on excitable gene circuits. arXiv:1605.09328 (2016)

  45. Warren, P.B., ten Wolde, P.R.: Chemical models of genetic toggle switches. J. Phys. Chem. B. 109, 6812–6823 (2005)

    Article  Google Scholar 

Download references

Acknowledgements

Funding was provided by Directorate for Mathematical and Physical Sciences (Grant Nos. 1413437 and 1412927.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William Ott.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azencott, R., Geiger, B. & Ott, W. Large Deviations for Gaussian Diffusions with Delay. J Stat Phys 170, 254–285 (2018). https://doi.org/10.1007/s10955-017-1909-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10955-017-1909-5

Keywords

Mathematics Subject Classification

Navigation