Workflow of the subnetwork extraction. First, single and combined z-scores are calculated from the phosphoproteomics data set and subsequently mapped on an interaction network (orange nodes). Proteins that do not occur in the interaction network are stored in a separate list (violet node). For the genetic algorithm (GA) procedure the network is encoded into a binary vector, where 1 codes for the associated node being active (i.e. part of a regulated subnetwork) and 0 inactive. The GA runs for a defined number of generations (exemplarily, the two-point crossover step in combination with a single-point mutation is depicted), and the strongest individual of the final generation encodes for the globally best achievable solution (here, this would be a subnetwork containing six nodes and a single-node network). Finally, the global rank (GR) significance test is performed on both extracted subnetworks and single nodes (or-more generally-single-node subnetworks) resulting in a set of significantly regulated subnetworks (only one in the depicted example).