Abstract

Constraint-based modelling can mechanistically simulate the behaviour of a biochemical system, permitting hypotheses generation, experimental design and interpretation of experimental data, with numerous applications, especially 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 each context. However, existing model extraction algorithms are unable to ensure that a context-specific model is thermodynamically flux consistent. This protocol introduces XomicsToModel, a semiautomated 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. One of the key advantages of the XomicsToModel pipeline is its ability to seamlessly incorporate omics data into metabolic reconstructions, ensuring not only mechanistic accuracy but also physicochemical consistency. This functionality allows for more accurate metabolic simulations and predictions across different biological contexts, enhancing its utility in diverse research fields, including systems biology, drug development, and personalised medicine. The XomicsToModel pipeline is exemplified for extraction of a specific metabolic model from a generic metabolic model; it enables omics data integration and extraction of physicochemically consistent mechanistic models from any generic biochemical network. It can be implemented by anyone who has basic MATLAB programming skills and the fundamentals of constraint-based modelling. Key pointsXomicsToModel is a semi-automated pipeline that integrates bibliomic, transcriptomic, proteomic, and metabolomic data with a generic genome-scale metabolic reconstruction or model. It enables the seamless incorporation of multi-omics datasets into metabolic reconstructions, ensuring mechanistic accuracy and physicochemical consistency.