Figure 5

A network target perspective for understanding the mechanisms of multicomponent synergy. a. Two agents targeting a protein complex, the feedback loop or crosstalk in a signaling network (the left figure) may have the shortest path distance and obtain high NIMS synergy score compared to those do not (the right figure). b. Two agents targeting hub or betweenness nodes (the left figure) may produce higher synergism than the combinations targeting peripheral nodes (the right figure). c. Two agents targeting two compensatory modules related to one disease or the similar diseases (the left figure) may produce higher synergism than those targeting two unrelated modules from unrelated diseases (the right figure). Dashed lines represent direct or indirect connections in a network. Blue or red nodes denote the responsive genes of two agents respectively.