Genome-scale metabolic network reconstructions in microorganisms have been formulated and studied for about 8 years. The constraint-based approach has shown great promise in analyzing the systemic properties of these network reconstructions. Notably, constraint-based models have been used successfully to predict the phenotypic effects of knock-outs and for metabolic engineering. The inherent uncertainty in both parameters and variables of large-scale models is significant and is well suited to

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... tudy by Monte Carlo sampling of the solution space. These techniques have been applied extensively to the reaction rate (flux) space of networks, with more recent work focusing on dynamic/kinetic properties. Monte Carlo sampling as an analysis tool has many advantages, including the ability to work with missing data, the ability to apply post-processing techniques, and the ability to quantify uncertainty and to optimize experiments to reduce uncertainty. We present an overview of this emerging area of research in systems biology.