Abstract

BackgroundIntrinsic fluctuations due to the stochastic nature of biochemical reactions can have large effects on the response of biochemical networks. This is particularly true for pathways that involve transcriptional regulation, where generally there are two copies of each gene and the number of messenger RNA (mRNA) molecules can be small. Therefore, there is a need for computational tools for developing and investigating stochastic models of biochemical networks.ResultsWe have developed the software package Biochemical Network Stochastic Simulator (BioNetS) for efficiently and accurately simulating stochastic models of biochemical networks. BioNetS has a graphical user interface that allows models to be entered in a straightforward manner, and allows the user to specify the type of random variable (discrete or continuous) for each chemical species in the network. The discrete variables are simulated using an efficient implementation of the Gillespie algorithm. For the continuous random variables, BioNetS constructs and numerically solves the appropriate chemical Langevin equations. The software package has been developed to scale efficiently with network size, thereby allowing large systems to be studied. BioNetS runs as a BioSpice agent and can be downloaded from . BioNetS also can be run as a stand alone package. All the required files are accessible from .ConclusionsWe have developed BioNetS to be a reliable tool for studying the stochastic dynamics of large biochemical networks. Important features of BioNetS are its ability to handle hybrid models that consist of both continuous and discrete random variables and its ability to model cell growth and division. We have verified the accuracy and efficiency of the numerical methods by considering several test systems.

Highlights

  • Intrinsic fluctuations due to the stochastic nature of biochemical reactions can have large effects on the response of biochemical networks

  • We have developed Biochemical Network Stochastic Simulator (BioNetS) to be a reliable tool for studying the stochastic dynamics of large biochemical networks

  • One particular concern is the accuracy of the Euler methods. While these methods are only of order ∆t, we show that when the approximations that lead to the chemical Langevin equations are valid, the difference between the numerical solutions of the stochastic differential equations (SDEs) and the exact discrete Gillespie method are negligible

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Summary

Results

We have developed the software package Biochemical Network Stochastic Simulator (BioNetS) for efficiently and accurately simulating stochastic models of biochemical networks. BioNetS has a graphical user interface that allows models to be entered in a straightforward manner, and allows the user to specify the type of random variable (discrete or continuous) for each chemical species in the network. The discrete variables are simulated using an efficient implementation of the Gillespie algorithm. For the continuous random variables, BioNetS constructs and numerically solves the appropriate chemical Langevin equations. The software package has been developed to scale efficiently with network size, thereby allowing large systems to be studied. BioNetS runs as a BioSpice agent and can be downloaded from http://www.biospice.org. BioNetS can be run as a stand alone package. All the required files are accessible from http://x.amath.unc.edu/BioNetS

Conclusions
Background
Results and discussion
Glass L
Keller A
19. Hume D
24. Bialek W
35. Gardiner C: Handbook of stochastic methods
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