Figure 3

Analysis of hub overlaps. (a) Venn diagram describing hub overlaps between networks. Shaded areas represent composite hubs. (b) Fold enrichments of hub overlaps (O) between two networks relative to random expectation. The bars above the line (where O = 1) show that overlapping hubs between the two networks are more than expected. The schematic above the first three bars shows that action networks tend to share the same hubs. One of the tri-hubs is Idh1p, an isocitrate dehydrogenase involved in the tricarboxylic acid cycle connecting a number of different pathways [7]. It is also involved in a number of complexes, and is thus co-expressed with many other genes [5,6,40,49]. In this schematic, the solid circle represents the composite hub; open circles represent different proteins; black solid lines represent interaction relationships; red dashed lines represent co-expression relationships; green dashed arrows represent metabolic reactions. The schematic above the last two bars shows that the regulatory network uses a distinct set of hubs. For example, Swi4p is a major TF regulating the yeast cell cycle [50]. However, it is not a hub in any of the action networks. In this schematic, the solid circle represents the regulatory hub; open circles represent different proteins; black solid arrows represent regulatory relationships. P values measure the significance of the differences between the observed overlaps and the random expectation. The random expectation was calculated as described in Materials and methods. P values in this figure and all following figures were calculated using the cumulative binomial distribution (Additional data file 1). Met, the metabolic network; Int, the interaction network; Exp, the co-expression network; and Reg, the regulatory network (in Figures 2 and 3, we only consider the regulator population in the regulatory network).