Figure 5.

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. (a) Bridges. The schematic shows that a bridge consists of four proteins: T1 regulates T2 and P1; T2 regulates P2. For example, Fol2p and Pho8p are two subsequent enzymes involved in the folate biosynthesis pathway [7]. FOL2 is regulated by Yox1p [9]. PHO8 is regulated by Pho4p [56]. Yox1p also regulates PHO4 [9]. The P value in the figure indicates the significance of the different between the fraction of bridges between all disconnected enzyme pairs and the random expectation (Table 3 in Additional data file 1). The regression equation for Met-Reg: F = 0.003k + 0.18; R = 0.56; P < 0.01. The regression equation for Int-Reg: F = -0.01k + 0.19; R = 0.74; P < 10^-3. The regression equation for Exp-Reg: F = -0.01k + 0.24; R = 0.93; P < 10^-9. P values here measure the significance of the correlation (R) in regression. (b) Composite motifs in the combined network of Met-Exp (that is co-expression motifs and shifted motifs). The schematic shows that composite motifs in Met-Exp consist of two proteins: P1 and P2. P1 and P2 have a distance of k in the metabolic network. They also have an expression relationship (co-expressed or others) in the co-expression network. The P value indicates that the fraction of protein pairs in shifted motifs in Met-Exp is significantly higher than expected. The regression equation for Met-Exp: F = 0.002k + 0.0037; R = 0.92; P < 10^-8. Met, the metabolic network; Int, the interaction network; Exp, the co-expression network; and Reg, the regulatory network.