Ahmadian, Mansooreh2020-08-052020-08-052020-08-04vt_gsexam:27199http://hdl.handle.net/10919/99481A complex network of genes and proteins governs the robust progression through cell cycles in the presence of inevitable noise. Stochastic modeling is viewed as a key paradigm to study the effects of intrinsic and extrinsic noise on the dynamics of biochemical networks. A detailed quantitative description of such complex and multiscale networks via stochastic modeling poses several challenges. First, stochastic models generally require extensive computations, particularly when applied to large networks. Second, the accuracy of stochastic models is highly dependent on the quality of the parameter estimation based on experimental observations. The goal of this dissertation is to address these problems by developing new efficient methods for modeling and simulation of stochastic effects in biochemical systems. Particularly, a hybrid stochastic model is developed to represent a detailed molecular mechanism of cell cycle control in budding yeast cells. In a single multiscale model, the proposed hybrid approach combines the advantages of two regimes: 1) the computational efficiency of a deterministic approach, and 2) the accuracy of stochastic simulations. The results show that this hybrid stochastic model achieves high computational efficiency while generating simulation results that match very well with published experimental measurements. Furthermore, a new hierarchical deep classification (HDC) algorithm is developed to address the parameter estimation problem in a monomolecular system. The HDC algorithm adopts a neural network that, via multiple hierarchical search steps, finds reasonably accurate ranges for the model parameters. To train the neural network in the presence of experimental data scarcity, the proposed method leverages the domain knowledge from stochastic simulations to generate labeled training data. The results show that the proposed HDC algorithm yields accurate ranges for the model parameters and highlight the potentials of model-free learning for parameter estimation in stochastic modeling of complex biochemical networks.ETDIn CopyrightCell Cycle ModelingHybrid Stochastic ModelingCell size controlParameter estimationNeural networkTheory-guided machine learningDissertation