Combining Flux Balance Analysis and Model Checking for Metabolic Network Validation and Analysis.

Several human diseases are caused by metabolism defects. Discovering the mechanisms that govern the onset and progression of human metabolism-related diseases is not a straightforward process. Computational approaches, such as the flux balance analysis, have been successfully used to extract useful knowledge on the metabolic dysregulation processes from genome-scale network models. In this work, we propose a novel approach which integrates constraint-based techniques with model checking methods, with the aim to extract relevant qualitative information from a metabolic network model. As a case study, we applied our methodology to the simulation and analysis of the primary hyperoxaluria type I, an inherited disease in which the lack of a particular liver enzyme causes the kidney to accumulate excessive amounts of oxalate.