We assessed whether a validated PCL had strong, selective, but unexpected connections to 3,333 annotated small molecule compounds. To focus on unexpected connections, we identified all compounds that connected to a validated PCL at τ ≥ 98 of which the given compound was not a member and whose members' gene targets did not overlap with the given compounds' gene targets. For each compound, we computed its PCL selectivity as the fraction of the 171 PCLs to which it failed to connect with τ ≥ 90 and considered only compounds with selectivity of at least 0.9. We identified 225 novel connections between drugs and validated PCLs, corresponding to 132 drugs (3.9% of total assessed). We applied the same analysis to 2,418 unannotated but transcriptionally active compounds and identified 194 strong, selective connections corresponding to 111 compounds (4.6% of total assessed).
