Integration of proteomic data with genome‐scale metabolic models: A methodological overview

The integration of proteomics data with constraint‐based reconstruction and analysis (COBRA) models plays a pivotal role in understanding the relationship between genotype and phenotype and bridges the gap between genome‐level phenomena and functional adaptations. Integrating a generic genome‐scale model with information on proteins enables generation of a context‐specific metabolic model which improves the accuracy of model prediction. This review explores methodologies for incorporating proteomics data into genome‐scale models. Available methods are grouped into four distinct categories based on their approach to integrate proteomics data and their depth of modeling. Within each category section various methods are introduced in chronological order of publication demonstrating the progress of this field. Furthermore, challenges and potential solutions to further progress are outlined, including the limited availability of appropriate in vitro data, experimental enzyme turnover rates, and the trade‐off between model accuracy, computational tractability, and data scarcity. In conclusion, methods employing simpler approaches demand fewer kinetic and omics data, consequently leading to a less complex mathematical problem and reduced computational expenses. On the other hand, approaches that delve deeper into cellular mechanisms and aim to create detailed mathematical models necessitate more extensive kinetic and omics data, resulting in a more complex and computationally demanding problem. However, in some cases, this increased cost can be justified by the potential for more precise predictions.