DOI
https://doi.org/10.25772/JQ6K-3824
Defense Date
2011
Document Type
Thesis
Degree Name
Master of Science
Department
Bioinformatics
First Advisor
Paul Brooks
Abstract
Metabolites consumed and produced by microorganisms for mass and energy conservation may cause changes in a microorganism’s environment. The microorganisms are unable to tolerate a particular environment for a long period. They may leave their old existence to find a new environment to sustain life. Essentially, organisms need to maintain their metabolic processes to survive in the new environment. Limitations of experimental studies to explore cell functions and regulations in detail result in insufficient information to explain processes of metabolic expressions under environments of organisms. Consequently, mathematical modeling and computer simulations have been conducted to combine all possible cellular metabolic fluxes into single or multiple connected networks. Metabolic modeling based on linear programming (LP) subjected to constraints with an optimization approach is often applied metabolic reconstruction. The LP objective function is maximized to obtain an optimal value of biomass flux. Optimal solutions in LP problems can be used to explain how metabolites function in metabolic reactions. As an LP problem may have many optimal solutions, this study proposes a method for enumerating all alternate optimal solutions to evaluate important reactions of metabolic pathways in microorganisms. The algorithm for generating alternate optimal solutions is implemented in MetModelGUI, a Java-based software for creating and analyzing metabolic reconstructions. The algorithm is applied to models of five microorganisms: Trypanosoma cruzi, Thermobifida fusca, Helicobacter pylori, Cryptococcus neoformans and Clostridium thermocellum. The results are analyzed using principal component analysis, and insight into the essential and non-essential pathways for each organism is derived
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
December 2011