Stochastic modelling of biochemical systems of multi-step reactions using a simplified two-variable model
Web of Science
AuthorWu, Q; Smith-Miles, K; Zhou, T; Tian, T
Source TitleBMC Systems Biology
University of Melbourne Author/sSmith-Miles, Kate
AffiliationSchool of Mathematics and Statistics
Document TypeJournal Article
CitationsWu, Q., Smith-Miles, K., Zhou, T. & Tian, T. (2013). Stochastic modelling of biochemical systems of multi-step reactions using a simplified two-variable model. BMC SYSTEMS BIOLOGY, 7 (SUPPL4), https://doi.org/10.1186/1752-0509-7-S4-S14.
Access StatusOpen Access
BACKGROUND: A fundamental issue in systems biology is how to design simplified mathematical models for describing the dynamics of complex biochemical reaction systems. Among them, a key question is how to use simplified reactions to describe the chemical events of multi-step reactions that are ubiquitous in biochemistry and biophysics. To address this issue, a widely used approach in literature is to use one-step reaction to represent the multi-step chemical events. In recent years, a number of modelling methods have been designed to improve the accuracy of the one-step reaction method, including the use of reactions with time delay. However, our recent research results suggested that there are still deviations between the dynamics of delayed reactions and that of the multi-step reactions. Therefore, more sophisticated modelling methods are needed to accurately describe the complex biological systems in an efficient way. RESULTS: This work designs a two-variable model to simplify chemical events of multi-step reactions. In addition to the total molecule number of a species, we first introduce a new concept regarding the location of molecules in the multi-step reactions, which is the second variable to represent the system dynamics. Then we propose a simulation algorithm to compute the probability for the firing of the last step reaction in the multi-step events. This probability function is evaluated using a deterministic model of ordinary differential equations and a stochastic model in the framework of the stochastic simulation algorithm. The efficiency of the proposed two-variable model is demonstrated by the realization of mRNA degradation process based on the experimentally measured data. CONCLUSIONS: Numerical results suggest that the proposed new two-variable model produces predictions that match the multi-step chemical reactions very well. The successful realization of the mRNA degradation dynamics indicates that the proposed method is a promising approach to reduce the complexity of biological systems.
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