Integrating -omics Data into Genome-scale Metabolic Network Models: Principles and Challenges

At genome scale, it is not yet possible to devise detailed kinetic models for metabolism because data on the biochemistry are too sparse. Predictive large-scale models for metabolism most commonly use the constraint-based framework, in which network structures constrain possible metabolic phenotypes at steady state. However, these models commonly leave many possibilities open, making them less predictive than desired. With increasingly available -omics data, it is appealing to increase the predictive power of constraint-based models (CBMs) through data integration. Many corresponding methods have been developed, but data integration is still a challenge and existing methods perform less well than expected. Here, we review main approaches for the integration of different types of -omics data into CBMs focussing on the methods' assumptions and limitations. We argue that key assumptions - often derived from single-enzyme kinetics - do not generally apply in the context of networks, thereby explaining current limitations. Emerging methods bridging CBMs and biochemical kinetics may allow for -omics data integration in a common framework to provide more accurate predictions.