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Parameter estimation methods for biological systems

dc.contributor.advisorWu, FangXiangen_US
dc.contributor.committeeMemberShi, Yangen_US
dc.contributor.committeeMemberDolovich, Allanen_US
dc.contributor.committeeMemberBugg, Jamesen_US
dc.contributor.committeeMemberChen, Lien_US
dc.creatorMu, Leien_US
dc.date.accessioned2010-03-30T14:01:38Zen_US
dc.date.accessioned2013-01-04T04:27:44Z
dc.date.available2011-04-13T08:00:00Zen_US
dc.date.available2013-01-04T04:27:44Z
dc.date.created2010-03en_US
dc.date.issued2010-03en_US
dc.date.submittedMarch 2010en_US
dc.description.abstractThe inverse problem of modeling biochemical processes mathematically from measured time course data falls into the category of system identification and parameter estimation. Analyzing the time course data would provide valuable insights into the model structure and dynamics of the biochemical system. Based on the types of biochemical reactions, such as metabolic networks and genetic networks, several modeling frameworks have been proposed, developed and proved effective, including the Michaelis-Menten equation, the Biochemical System Theory (BST), etc. One bottleneck in analyzing the obtained data is the estimation of parameter values within the system model. As most models for molecular biological systems are nonlinear with respect to both parameters and system state variables, estimation of parameters in these models from experimental measurement data is thus a nonlinear estimation problem. In principle, all algorithms for nonlinear optimization can be used to deal with this problem, for example, the Gauss-Newton iteration method and its variants. However, these methods do not take the special structures of biological system models into account. When the number of parameters to be determined increases, it will be challenging and computationally expensive to apply these conventional methods. In this research, several methods are proposed for estimating parameters in two classes of widely used biological system models: the S-system model and the linear fractional model (LFM), by utilizing their structure specialties. For the S-system, two estimation methods are designed. 1) Based on the two-term structure (production and degradation) of the model, an alternating iterative least squares method is proposed. 2) A separation nonlinear least squares method is proposed to deal with the partially linear structure of the model. For the LFM, two estimation methods are provided. 1) The separation nonlinear least squares method can also be adopted to treat the partially linear structure of the LFM, and moreover a modified iterative version is included. 2) A special strategy using the separation principle and the weighted least squares method is implemented to turn the cost function into a quadratic form and thus the estimates for parameters can be analytically solved. Simulation results have demonstrated the effectiveness of the proposed methods, which have shown better performance in terms of estimation accuracy and computation time, compared with those conventional nonlinear estimation methods.en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-03302010-140138en_US
dc.language.isoen_USen_US
dc.subjectparameter estimationen_US
dc.subjectleast squaresen_US
dc.subjectoptimizationen_US
dc.subjectlinear fractional model (LFM)en_US
dc.subjectseparation methoden_US
dc.subjectnonlinear biological systemen_US
dc.subjectS-systemen_US
dc.subjecttime course dataen_US
dc.titleParameter estimation methods for biological systemsen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentMechanical Engineeringen_US
thesis.degree.disciplineMechanical Engineeringen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US

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