Fig 1. Algorithm for finding a medium with the maximal separation between dN/dS values of essential and nonessential genes.

Metabolic models (a) are first preprocessed and databases added to them, to support fast computation of essential genes (b). Simulated Annealing (c) is the first stage of optimization and the resulting medium found is further purified from redundant compounds (d), resulting in the two desired media: those which maximize the differential conservation of essential genes (e) and those which maximize the differential conservation of the nonessential genes (f).