Fig. 1

The pipeline used to assemble and to sort the KP-Net, and the KP-Net bow tie structure. a The steps followed to elucidate the KP-Net hierarchical structure starting from the different sources used to collect kinase-protein and phosphatase-protein interactions, passing through the data annotation procedure and filtering criteria applied to select high quality PDIs, to the assembly and sorting of the KP-Net by the VS algorithm. b The bow tie structure of the KP-Net showing how KPs are classified in top, core and bottom layers. Top layer KPs control core layer KPs; top and core layer KPs control bottom layer KPs and KPs in the three layers control proteins in the substrates layer formed of proteins that are not KPs and of KPs having no substrates. Numbers between parentheses represent number of nodes in each layer. Arrows represent directed interactions (red: phosphorylation, green: dephosphorylation and black: both). Percentages designate percentage of interactions within and between layers