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dc.contributor.authorWang, Shuoen_US
dc.date.accessioned2018-03-31T06:00:16Z
dc.date.available2018-03-31T06:00:16Z
dc.date.issued2016-10-06
dc.identifier.othervt_gsexam:8938en_US
dc.identifier.urihttp://hdl.handle.net/10919/82717
dc.description.abstractStochastic effects in cellular systems are usually modeled and simulated with Gillespie's stochastic simulation algorithm (SSA), which follows the same theoretical derivation as the chemical master equation (CME), but the low efficiency of SSA limits its application to large chemical networks. To improve efficiency of stochastic simulations, Haseltine and Rawlings proposed a hybrid of ODE and SSA algorithm, which combines ordinary differential equations (ODEs) for traditional deterministic models and SSA for stochastic models. In this dissertation, accuracy analysis, efficient implementation strategies, and application of of Haseltine and Rawlings's hybrid method (HR) to a budding yeast cell cycle model are discussed. Accuracy of the hybrid method HR is studied based on a linear chain reaction system, motivated from the modeling practice used for the budding yeast cell cycle control mechanism. Mathematical analysis and numerical results both show that the hybrid method HR is accurate if either numbers of molecules of reactants in fast reactions are above certain thresholds, or rate constants of fast reactions are much larger than rate constants of slow reactions. Our analysis also shows that the hybrid method HR allows for a much greater region in system parameter space than those for the slow scale SSA (ssSSA) and the stochastic quasi steady state assumption (SQSSA) method. Implementation of the hybrid method HR requires a stiff ODE solver for numerical integration and an efficient event-handling strategy for slow reaction firings. In this dissertation, an event-handling strategy is developed based on inverse interpolation. Performances of five wildly used stiff ODE solvers are measured in three numerical experiments. Furthermore, inspired by the strategy of the hybrid method HR, a hybrid of ODE and SSA stochastic models for the budding yeast cell cycle is developed, based on a deterministic model in the literature. Simulation results of this hybrid model match very well with biological experimental data, and this model is the first to do so with these recently available experimental data. This study demonstrates that the hybrid method HR has great potential for stochastic modeling and simulation of large biochemical networks.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis Item is protected by copyright and/or related rights. Some uses of this Item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjecthybrid stochastic simulation algorithmen_US
dc.subjectlinear chain reaction systemen_US
dc.subjectordinary differential equationen_US
dc.subjectcell cycle modelen_US
dc.titleAnalysis and Application of Haseltine and Rawlings's Hybrid Stochastic Simulation Algorithmen_US
dc.typeDissertationen_US
dc.contributor.departmentComputer Scienceen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineComputer Science and Applicationsen_US
dc.contributor.committeechairCao, Yangen_US
dc.contributor.committeememberRathinam, Muruhanen_US
dc.contributor.committeememberOnufriev, Alexeyen_US
dc.contributor.committeememberHoops, Stefanen_US
dc.contributor.committeememberWatson, Layne T.en_US


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