Document Type

Article

Publication Date

7-27-2012

First Advisor

Allen G. Holder

Abstract

Flux Balance Analysis (FBA) is a widely used computational model for studying the metabolic pathways of cells and the role individual metabolites and reactions play in maintaining cell function. However, the successes of FBA have been limited by faulty biological assumptions and computational imperfections. We introduce Robust Analysis of Metabolic Pathways (RAMP) to provide a more theoretically sound and computationally accurate model of cellular metabolism. RAMP overcomes the faulty assumptions of traditional FBA by allowing deviation from steady-state and accounting for variability across a cellular culture. Computationally, RAMP more successfully predicts the lethality of gene knockouts and reduces degeneracy in optimal ux values. Analytical results establish the stability of RAMP under perturbations in modeling parameters. The inclusion of new modeling parameters in RAMP opens the possibility of modeling different cellular cultures in a wider range of conditions, including non- optimized cultures. We conclude that RAMP is an improvement over traditional FBA and deserves further study.

Comments

MSTR 12-02

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