Figure 3: Target prediction and network information content.
From: Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data
(a) We performed three sets of optimizations to model the effect of mTOR inhibition: (i) with real K/P interactions and the expected drug target (mTOR); (ii) with the real interactions but another drug’s targets (MP2K1, MP2K2); and (iii) with three separate randomized sets of K/P interactions and the expected target. (b) Population average scores for each of the two mTOR inhibitors. (c) Simplified representation of the resulting networks (20% tolerance; full networks shown in Supplementary Fig. 6). The size of the nodes reflects the number of K/P or sites perturbed, at a distance d from the drug target. Real network/correct target: 33 out of 34 perturbed nodes connected to mTOR, average shortest path length of 4.3; 92 nodes in total. One of the three randomized networks/real target: 30 out of 34 perturbed nodes connected to mTOR, average shortest path length of 4.9; 83 nodes in total. Real network/incorrect target: 30 out of 34 perturbed nodes connected to MP2K1/MP2K2, average shortest path length of 8.1; 141 nodes in total. Most sites are connected to the designated targets in all cases but the paths are shorter with the correct target than with the incorrect ones. The random networks show a major difference in terms of number of sites explained directly by the drug target or its first neighbours (14 sites for the real network versus 4 sites for this random network).
