XomicsToModel: Omics data integration and generation of thermodynamically consistent metabolic models

AbstractConstraint-based modelling can mechanistically simulate the behaviour of a biochemical system, permitting hypotheses generation, experimental design and interpretation of experimental data, with numerous applications, including modelling of metabolism. Given a generic model, several methods have been developed to extract a context-specific, genome-scale metabolic model by incorporating information used to identify metabolic processes and gene activities in a given context. However, existing model extraction algorithms are unable to ensure that the context-specific model is thermodynamically feasible. This protocol introducesXomicsToModel, a semi-automated pipeline that integrates bibliomic, transcriptomic, proteomic, and metabolomic data with a generic genome-scale metabolic reconstruction, or model, to extract a context-specific, genome-scale metabolic model that is stoichiometrically, thermodynamically and flux consistent. TheXomicsToModelpipeline is exemplified for extraction of a specific metabolic model from a generic metabolic model, but it enables omics data integration and extraction of physicochemically consistent mechanistic models from any generic biochemical network. With all input data fully prepared, algorithmic completion of the pipeline takes ~10 min, however manual review of intermediate results may also be required, e.g., when inconsistent input data lead to an infeasible model.