Protein-centric representation of the biotin metabolism. The protein-centric or reaction graph representation which was used in our study has enzymes as vertices and reactants as edges. EC 188.8.131.52 is a neighbor of EC 184.108.40.206 because there is an edge leading from EC 220.127.116.11 to EC 18.104.22.168. In the same manner, EC 22.214.171.124 is a neighbor of 126.96.36.199. In the biotin metabolism example there are 8 enzyme neighbor pairs. Note that in our definition an edge can consist of one or more compounds and there can only be one edge in each direction between two enzymes. The edges in blue font, representing CO2, between EC 188.8.131.52 and EC 184.108.40.206, are eliminated when the 20 most promiscuous compounds are removed from the network.