Figure 1
Cumulative silencing time distribution of drug targets and non-target proteins.
The diagram shows the cumulative distribution of the normalized number of proteins with given silencing times, which are drug targets with known side effects (blue dashed line), which are drug targets without known side effects (red solid line) and which are not drug targets (green dotted line). The number of proteins was normalized by dividing the number of proteins in each silencing time range by the total number of proteins allowing a better comparison. The total number of drug targets with and without side effects and non-target proteins was 495, 1,231 and 10,713, respectively. The human interactome containing 12,439 proteins and 174,666 edges was built from the STRING database46, 1,726 human drug targets were obtained from the DrugBank database47 and 99,423 drug-side effect pairs were taken from the SIDER database2. Silencing times were calculated separately for every protein/drug target with the Turbine program35 as described in the Methods section using a starting energy of 1,000 and a dissipation value of 5 units. Statistical analysis was performed using the Mann-Whitney (Wilcoxon rank sum) test function of the R package56. There was a statistically significant difference (p = 1.677e-5) between the silencing times of drug targets with known side effects and the silencing times of drug targets without reported side effects. The difference between the silencing times of drug targets and non-target proteins was also statistically significant (p = 2.2e-16).
