We present a thorough in silico analysis and optimization of the genome-scale metabolic model of the mycolic acid pathway in M. tuberculosis. We apply and further extend meGDMO to account for finer sensitivity analysis and post-processing analysis, thanks to the combination of statistical evaluation of strains robustness, and clustering analysis to map the phenotype-genotype relationship among Pareto optimal strains. In the first analysis scenario, we find 12 Pareto-optimal single gene set knockout, which completely shut down the pathway, hence critically reducing the pathogenicity of M. tuberculosis; as well as 34 genotypically different strains in which the production of mycolic acid is severely reduced.
Metabolic circuit design automation by multi-objective BioCAD
Conca P.;Carapezza G.;Costanza J.;Nicosia G.
2016-01-01
Abstract
We present a thorough in silico analysis and optimization of the genome-scale metabolic model of the mycolic acid pathway in M. tuberculosis. We apply and further extend meGDMO to account for finer sensitivity analysis and post-processing analysis, thanks to the combination of statistical evaluation of strains robustness, and clustering analysis to map the phenotype-genotype relationship among Pareto optimal strains. In the first analysis scenario, we find 12 Pareto-optimal single gene set knockout, which completely shut down the pathway, hence critically reducing the pathogenicity of M. tuberculosis; as well as 34 genotypically different strains in which the production of mycolic acid is severely reduced.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
