Figure 7.

A toy network illustrating how to measure indirect effects. In this toy PPI network, there are two disease proteins, a red (D degree = 3) and a black (D = 7) one. Their interacting partners (IPs) are colorful: the green (D = 2) and the yellow (D = 5) nodes mediate two-step-long indirect effects between disease proteins, the blue ones do not. White nodes are not IPs. The PPI network contains all nodes, the DPIP network contains all colorful nodes but no links among IPs, while the IP network contains only IPs and the links among them. The strength of the effect from the red node to the green one is 1/2, and from the green to the black node it equals 1/7, thus, the red-green-black pathway is of strength 1/14. Similarly, the red-yellow-black pathway is of strength 1/5*1/7 = 1/35. Additively, the two-step-long indirect effects from red to black equal 1/14+1/35 = 49/490 = 1/10. From black to red, the strength of two-step-long indirect influence is (1/5*1/3)+(1/2*1/3) = 7/30. The summed mutual dependence equals 7/30+1/10 = 10/30 = 1/3. The relative contribution of the two mediator proteins are 1/15+1/35 = 50/525 = 0.095 (yellow) and 1/14+1/6 = 20/84 = 5/21 = 0.238 (green). Figure drawn by [38].