Tau leaping of stiff stochastic chemical systems via local central limit approximation

Stiffness manifests in stochastic dynamic systems in a more complex manner than in deterministic systems; it is not only important for a time-stepping method to remain stable but it is also important for the method to capture the asymptotic variances accurately. In the context of stochastic chemical systems, time stepping methods are known as tau leaping. Well known existing tau leaping methods have shortcomings in this regard. The implicit tau method is far more stable than the trapezoidal tau method but underestimates the asymptotic variance. On the other hand, the trapezoidal tau method which estimates the asymptotic variance exactly for linear systems suffers from the fact that the transients of the method do not decay fast enough in the context of very stiff systems. We propose a tau leaping method that possesses the same stability properties as the implicit method while it also captures the asymptotic variance with reasonable accuracy at least for the test system S"[email protected]?S"2. The proposed method uses a central limit approximation (CLA) locally over the tau leaping interval and is referred to as the [email protected] The CLA predicts the mean and covariance as solutions of certain differential equations (ODEs) and for efficiency we solve these using a single time step of a suitable low order method. We perform a mean/covariance stability analysis of various possible low order schemes to determine the best scheme. Numerical experiments presented show that [email protected] performs favorably for stiff systems and that the [email protected] is also able to capture bimodal distributions unlike the CLA itself. The proposed [email protected] method uses a split implicit step to compute the mean update. We also prove that any tau leaping method employing a split implicit step converges in the fluid limit to the implicit Euler method as applied to the fluid limit differential equation.

[1]  Hana El-Samad,et al.  Reversible-equivalent-monomolecular tau: A leaping method for "small number and stiff" stochastic chemical systems , 2007, J. Comput. Phys..

[2]  Yucheng Hu,et al.  Highly accurate tau-leaping methods with random corrections. , 2009, The Journal of chemical physics.

[3]  D. Gillespie,et al.  Avoiding negative populations in explicit Poisson tau-leaping. , 2005, The Journal of chemical physics.

[4]  Philipp Thomas,et al.  How accurate are the nonlinear chemical Fokker-Planck and chemical Langevin equations? , 2011, The Journal of chemical physics.

[5]  Stewart N. Ethier,et al.  Generators and Markov Processes , 2008 .

[6]  Tiejun Li,et al.  Analysis of Explicit Tau-Leaping Schemes for Simulating Chemically Reacting Systems , 2007, Multiscale Model. Simul..

[7]  S. Ethier,et al.  Markov Processes: Characterization and Convergence , 2005 .

[8]  Muruhan Rathinam,et al.  The numerical stability of leaping methods for stochastic simulation of chemically reacting systems. , 2004, The Journal of chemical physics.

[9]  D. Gillespie Exact Stochastic Simulation of Coupled Chemical Reactions , 1977 .

[10]  D. Gillespie Markov Processes: An Introduction for Physical Scientists , 1991 .

[11]  Muruhan Rathinam,et al.  Consistency and Stability of Tau-Leaping Schemes for Chemical Reaction Systems , 2005, Multiscale Model. Simul..

[12]  Antony Jameson,et al.  Solution of the Equation $AX + XB = C$ by Inversion of an $M \times M$ or $N \times N$ Matrix , 1968 .

[13]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[14]  M. Bennett,et al.  Transient dynamics of genetic regulatory networks. , 2007, Biophysical journal.

[15]  David F. Anderson,et al.  Error analysis of tau-leap simulation methods , 2009, 0909.4790.

[16]  Linda R Petzold,et al.  Efficient step size selection for the tau-leaping simulation method. , 2006, The Journal of chemical physics.

[17]  Antony Jameson,et al.  SOLUTION OF EQUATION AX + XB = C BY INVERSION OF AN M × M OR N × N MATRIX ∗ , 1968 .

[18]  Tobias Jahnke,et al.  Efficient simulation of discrete stochastic reaction systems with a splitting method , 2010 .

[19]  D. Gillespie A rigorous derivation of the chemical master equation , 1992 .

[20]  D. Gillespie A General Method for Numerically Simulating the Stochastic Time Evolution of Coupled Chemical Reactions , 1976 .

[21]  Sheldon M. Ross,et al.  Introduction to probability models , 1975 .

[22]  D. Gillespie Approximate accelerated stochastic simulation of chemically reacting systems , 2001 .

[23]  D. Vlachos,et al.  Binomial distribution based tau-leap accelerated stochastic simulation. , 2005, The Journal of chemical physics.

[24]  D. Gillespie The Chemical Langevin and Fokker−Planck Equations for the Reversible Isomerization Reaction† , 2002 .

[25]  D. Sherrington Stochastic Processes in Physics and Chemistry , 1983 .

[26]  Muruhan Rathinam,et al.  Stiffness in stochastic chemically reacting systems: The implicit tau-leaping method , 2003 .

[27]  Muruhan Rathinam,et al.  Integral tau methods for stiff stochastic chemical systems. , 2011, The Journal of chemical physics.

[28]  Chi-Tsong Chen,et al.  Linear System Theory and Design , 1995 .

[29]  P. Kloeden,et al.  Numerical Solution of Stochastic Differential Equations , 1992 .

[30]  N. Kampen,et al.  Stochastic processes in physics and chemistry , 1981 .

[31]  D. Gillespie The chemical Langevin equation , 2000 .

[32]  Peter Hänggi,et al.  Bistable systems: Master equation versus Fokker-Planck modeling , 1984 .

[33]  K. Burrage,et al.  Binomial leap methods for simulating stochastic chemical kinetics. , 2004, The Journal of chemical physics.

[34]  Carl D. Meyer,et al.  Matrix Analysis and Applied Linear Algebra , 2000 .