ArticleBMC bioinformatics2019
Analysis and remedy of negativity problem in hybrid stochastic simulation algorithm and its application.
Article in BMC bioinformatics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum.iScience · 2022Article
- Selected research articles from the 2018 International Workshop on Computational Network Biology: Modeling, Analysis, and Control (CNB-MAC).BMC bioinformatics · 2019Article
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2 authors.
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Abstract
backgroundThe hybrid stochastic simulation algorithm, proposed by Haseltine and Rawlings (HR), is a combination of differential equations for traditional deterministic models and Gillespie's algorithm (SSA) for stochastic models. The HR hybrid method can significantly improve the efficiency of stochastic simulations for multiscale biochemical networks. Previous studies on the accuracy analysis for a linear chain reaction system showed that the HR hybrid method is accurate if the scale difference between fast and slow reactions is above a certain threshold, regardless of population scales. However, the population of some reactant species might be driven negative if they are involved in both deterministic and stochastic systems.
resultsThis work investigates the negativity problem of the HR hybrid method, analyzes and tests it with several models including a linear chain system, a nonlinear reaction system, and a realistic biological cell cycle system. As a benchmark, the second slow reaction firing time is used to measure the effect of negative populations on the accuracy of the HR hybrid method. Our analysis demonstrates that usually the error caused by negative populations is negligible compared with approximation errors of the HR hybrid method itself, and sometimes negativity phenomena may even improve the accuracy. But for systems where negative species are involved in nonlinear reactions or some species are highly sensitive to negative species, the system stability will be influenced and may lead to system failure when using the HR hybrid method. In those circumstances, three remedies are studied for the negativity problem.
conclusionThe results of different models and examples suggest that the Zero-Reaction rule is a good remedy for nonlinear and sensitive systems considering its efficiency and simplicity.
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