Kinetic Parameter Estimation in Oscillatory Biochemical Systems

NABAVI, SEYEDBEHZAD. Kinetic Parameter Estimation in Oscillatory Biochemical Systems. (Under the direction of Cranos M. Williams.) Oscillatory pathways are among the most important classes of biochemical systems with examples such as circadian rhythms and cell cycles. Mathematical modeling of these highly interconnected biochemical networks is needed to meet numerous objectives such as investigating, predicting and controlling the dynamics of these systems. Identifying the kinetic parameters is essential in fully modeling the biorhythms. However, the kinetic parameters are not usually available from measurements and most of them have to be estimated by parameter fitting techniques. One of the issues with estimating kinetic parameters in oscillatory systems is the irregularities in the Least Square (LS) cost function surface caused by the periodicity of the measurements. These irregularities result in numerous local minima, which limit the performance of even some of the most robust global optimization algorithms. We proposed a parameter estimation framework to address these issues by integrating temporal information with periodic information embedded in the measurements used to estimate these parameters. This periodic information is used to propose a cost function with better surface properties leading to fewer local minima and better performance of global optimization algorithms. We verified for three oscillatory biochemical systems that our method results in increased ability to estimate accurate kinetic parameters as compared to the traditional LS cost function. We combine this cost function with an improved noise removal approach that leverages periodic characteristics embedded in the measurements to effectively reduce noise. The results provide strong evidence on the efficacy of this noise removal approach over the previous commonly used wavelet hardthresholding noise removal methods. This proposed optimization framework results in more accurate kinetic parameters that will eventually lead to biochemical models that are more accurate, predictable and controllable. c © Copyright 2011 by Seyedbehzad Nabavi All Rights Reserved Kinetic Parameter Estimation in Oscillatory Biochemical Systems by Seyedbehzad Nabavi A thesis submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Master of Science Electrical Engineering Raleigh, North Carolina 2011