Fig 2. Establishment of signaling-metabolic pathway protein (S-M) interconnections for construction of SMIN.

(A) Fourteen signaling (left) and six groups of metabolic pathways (right; grouping of 81 individual metabolic pathways) were selected from the KEGG database to develop the S-M interconnected network (SMIN) through PPI. Experimentally validated data from the STRING protein-interaction database were used to construct an initial HPPIN. The levels of interaction were restricted at the interactors of interactors to create the network resulting in four possible linking paths through which selected signaling and metabolic pathway proteins could be connected directly or through one, two and three PPI. (B) Conversion of interconnecting paths into network representation.