Abstract
MOTIVATION: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these models to represent cellular metabolism in specific conditions has been improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics data with other omics data sources into genome-scale models of metabolism have been developed. RESULTS: GIM(3)E (Gene Inactivation Moderated by Metabolism, Metabolomics and Expression) is an algorithm that enables the development of condition-specific models based on an objective function, transcriptomics and cellular metabolomics data. GIM(3)E establishes metabolite use requirements with metabolomics data, uses model-paired transcriptomics data to find experimentally supported solutions and provides calculations of the turnover (production/consumption) flux of metabolites. GIM(3)E was used to investigate the effects of integrating additional omics datasets to create increasingly constrained solution spaces of Salmonella Typhimurium metabolism during growth in both rich and virulence media. This integration proved to be informative and resulted in a requirement of additional active reactions (12 in each case) or metabolites (26 or 29, respectively). The addition of constraints from transcriptomics also impacted the allowed solution space, and the cellular metabolites with turnover fluxes that were necessarily altered by the change in conditions increased from 118 to 271 of 1397. AVAILABILITY: GIM(3)E has been implemented in Python and requires a COBRApy 0.2.x. The algorithm and sample data described here are freely available at: http://opencobra.sourceforge.net/ CONTACTS: brianjamesschmidt@gmail.com