Integration of comparative genomics with genome-scale metabolic modeling to investigate strain-specific phenotypical differences

Genome-scale metabolic reconstructions are powerful resources that allow translation biological knowledge and genomic information to phenotypical predictions using a number of constraint-based methods. This approach has been applied in recent years to gain deep insights into the cellular phenotype role of the genes at a systems-level, driving the design of targeted experiments and paving the way for knowledge-based synthetic biology. The identification of genetic determinants underlying the variability at the phenotypical level is crucial to understand the evolutionary trajectories of a bacterial species. Recently, genome-scale metabolic models of different strains have been assembled to highlight the intra-species diversity at the metabolic level. The strain-specific metabolic capabilities and auxotrophies can be used to identify factors related to the lifestyle diversity of a bacterial species. In this chapter, we present the computational steps to perform genome-scale metabolic modeling in the context of comparative genomics, and the different challenges related to this task.