In order to test the accuracy of PCL connections, we profiled 137 holdout compounds known to share a mechanism with one or more of 54 small-molecule PCLs, but which were not used in the construction of the PCL itself. We subjected the resulting signatures to connectivity analyses as described above and observed that for 41/54 classes (76%), the test compounds connected to their designated PCL in multiple cell types (Figure 4B). For an additional 7/54 (13%), a selective connection was observed in a single cell type. The remaining 6/54 (11%) did not reconnect at a threshold of t >90. Thus, 48 of the 54 assessed PCLs (89%) were considered validated in that they successfully connected to their corresponding holdout compound(s).
