Figure 4

Fraction (F) of all P1-P2 pairs at distance k in a given combined network in a particular composite motif. Horizontal dashed lines indicate the random expectation. Vertical dashed lines indicate connected pairs in combined networks. (a) Triangles. The schematic shows that a triangle consists of three proteins: the common regulator TF regulates both P1 and P2. In all schematics, circles represent TFs, and rectangles represent non-TF genes. For example, ADE5, 7 and ADE8 are two subsequent enzymes in the purine biosynthesis pathway [7]. They are co-regulated by BAS1 [51]. (b) Trusses. The schematic shows that a truss consists of four proteins: T1 regulates T2, P1 and P2; T2 regulates P1 and P2. For example, Cln1p and Cln2p are two subunits of the CDC28-associated complex [4]. They are co-regulated by Mbp1p and Swi4p [52]. Mbp1p also regulates SWI4 [8,53]. (c) Semi-trusses. A semi-truss is an incomplete truss: either T2 does not regulate P1, or T1 does not regulate P2. For example, RPL3 and RPL9A, components of the ribosome large subunit, are co-expressed [6]. They are co-regulated by Bdf1p [54]. Rap1p regulates both RPL3 and BDF1 [8,55]. We also examined the occurrence of triangles and trusses between protein pairs connected in more than one network, termed highly combined networks. We only considered semi-trusses to get better statistics, since the number of full trusses in highly combined networks is too small to be used. In all highly combined networks, triangles and semi-trusses are enriched between protein pairs connected in more than one network (Figure 8 in Additional data file 1). Met, the metabolic network; Int, the interaction network; Exp, the co-expression network; and Reg, the regulatory network.