Model Reduction of Multiscale Chemical Langevin Equations: A Numerical Case Study

Two very important characteristics of biological reaction networks need to be considered carefully when modeling these systems. First, models must account for the inherent probabilistic nature of systems far from the thermodynamic limit. Often, biological systems cannot be modeled with traditional continuous-deterministic models. Second, models must take into consideration the disparate spectrum of time scales observed in biological phenomena, such as slow transcription events and fast dimerization reactions. In the last decade, significant efforts have been expended on the development of stochastic chemical kinetics models to capture the dynamics of biomolecular systems, and on the development of robust multiscale algorithms, able to handle stiffness. In this paper, the focus is on the dynamics of reaction sets governed by stiff chemical Langevin equations, i.e., stiff stochastic differential equations. These are particularly challenging systems to model, requiring prohibitively small integration step sizes. We describe and illustrate the application of a semianalytical reduction framework for chemical Langevin equations that results in significant gains in computational cost.

[1]  T. Elston,et al.  Stochasticity in gene expression: from theories to phenotypes , 2005, Nature Reviews Genetics.

[2]  Vassilios Sotiropoulos,et al.  Synthetic tetracycline-inducible regulatory networks: computer-aided design of dynamic phenotypes , 2007, BMC Systems Biology.

[3]  J. Goutsias Quasiequilibrium approximation of fast reaction kinetics in stochastic biochemical systems. , 2005, The Journal of chemical physics.

[4]  Costas D Maranas,et al.  Elucidation and structural analysis of conserved pools for genome-scale metabolic reconstructions. , 2005, Biophysical journal.

[5]  M. Khammash,et al.  The finite state projection algorithm for the solution of the chemical master equation. , 2006, The Journal of chemical physics.

[6]  Tatsuo Shibata,et al.  Reducing the master equations for noisy chemical reactions , 2003 .

[7]  Yiannis N. Kaznessis,et al.  Models for synthetic biology , 2007, BMC Systems Biology.

[8]  Howard M. Salis,et al.  Numerical simulation of stochastic gene circuits , 2005, Comput. Chem. Eng..

[9]  S. Swain Handbook of Stochastic Methods for Physics, Chemistry and the Natural Sciences , 1984 .

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

[11]  P Borella,et al.  Sorbitol dehydrogenase from bovine lens: purification and properties. , 1997, Archives of biochemistry and biophysics.

[12]  P. Daoutidis,et al.  Nonlinear model reduction of chemical reaction systems , 2001 .

[13]  Yiannis N. Kaznessis,et al.  Multi-scale models for gene network engineering , 2006 .

[14]  Eric Vanden-Eijnden,et al.  Nested stochastic simulation algorithm for chemical kinetic systems with disparate rates. , 2005, The Journal of chemical physics.

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

[16]  Yiannis N Kaznessis,et al.  An equation-free probabilistic steady-state approximation: dynamic application to the stochastic simulation of biochemical reaction networks. , 2005, The Journal of chemical physics.

[17]  Bernhard O Palsson,et al.  The convex basis of the left null space of the stoichiometric matrix leads to the definition of metabolically meaningful pools. , 2003, Biophysical journal.

[18]  P. Swain,et al.  Stochastic Gene Expression in a Single Cell , 2002, Science.

[19]  Xenofon D. Koutsoukos,et al.  Verification of Biochemical Processes Using Stochastic Hybrid Systems , 2007, 2007 IEEE 22nd International Symposium on Intelligent Control.

[20]  H. Salis,et al.  Computer-aided design of modular protein devices: Boolean AND gene activation , 2006, Physical biology.

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

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

[23]  Prodromos Daoutidis,et al.  Non-linear reduction for kinetic models of metabolic reaction networks. , 2004, Metabolic engineering.

[24]  Brian Munsky,et al.  Reduction and solution of the chemical master equation using time scale separation and finite state projection. , 2006, The Journal of chemical physics.

[25]  Yiannis N Kaznessis,et al.  Model-driven designs of an oscillating gene network. , 2005, Biophysical journal.

[26]  M. Mavrovouniotis,et al.  Simplification of Mathematical Models of Chemical Reaction Systems. , 1998, Chemical reviews.

[27]  C. Rao,et al.  Stochastic chemical kinetics and the quasi-steady-state assumption: Application to the Gillespie algorithm , 2003 .

[28]  J. A. M. Janssen,et al.  The elimination of fast variables in complex chemical reactions. III. Mesoscopic level (irreducible case) , 1989 .

[29]  J. A. M. Janssen,et al.  The elimination of fast variables in complex chemical reactions. II. Mesoscopic level (reducible case) , 1989 .

[30]  Vassilios Sotiropoulos,et al.  SynBioSS: the synthetic biology modeling suite , 2008, Bioinform..

[31]  Guang Qiang Dong,et al.  Simplification of Stochastic Chemical Reaction Models with Fast and Slow Dynamics , 2007, Journal of biological physics.

[32]  Jeffrey W. Smith,et al.  Stochastic Gene Expression in a Single Cell , .

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

[34]  Vassilios Sotiropoulos,et al.  Multiscale Hy3S: Hybrid stochastic simulation for supercomputers , 2006, BMC Bioinformatics.

[35]  Prodromos Daoutidis,et al.  Decoupling of fast and slow variables in chemical Langevin equations with fast and slow reactions , 2006, 2006 American Control Conference.

[36]  S. Subramaniam,et al.  Reduced-order modelling of biochemical networks: application to the GTPase-cycle signalling module. , 2005, Systems biology.

[37]  D G Vlachos,et al.  Overcoming stiffness in stochastic simulation stemming from partial equilibrium: a multiscale Monte Carlo algorithm. , 2005, The Journal of chemical physics.

[38]  Hong Li,et al.  Efficient formulation of the stochastic simulation algorithm for chemically reacting systems. , 2004, The Journal of chemical physics.

[39]  Vassilios Sotiropoulos,et al.  An adaptive time step scheme for a system of stochastic differential equations with multiple multiplicative noise: chemical Langevin equation, a proof of concept. , 2008, The Journal of chemical physics.

[40]  Adam P Arkin,et al.  Fifteen minutes of fim: control of type 1 pili expression in E. coli. , 2002, Omics : a journal of integrative biology.

[41]  Linda R Petzold,et al.  The slow-scale stochastic simulation algorithm. , 2005, The Journal of chemical physics.

[42]  Michael A. Gibson,et al.  Efficient Exact Stochastic Simulation of Chemical Systems with Many Species and Many Channels , 2000 .

[43]  Yiannis Kaznessis,et al.  Accurate hybrid stochastic simulation of a system of coupled chemical or biochemical reactions. , 2005, The Journal of chemical physics.