We then computed the pairwise similarity (using WTCS) between signatures of the same perturbagen in different cell lines, yielding an N × N matrix of similarity values, where N is the number of cell lines in which the perturbagen gave a high-TAS signature. Next, we computed the median WTCS between each cell line and all others, yielding a vector of N median WTCS values (WTCSmed). We then computed the median of medians (MoM) and range of WTCSmed, yielding WTCSMoM and WTCSrange, metrics which indicate the aggregate similarity and the variability thereof between signatures of the same perturbagen in different cell lines. Perturbagens that give a single signature across multiple cell types should have high WTCSMoM and low WTCSrange values, respectively. To estimate significance, we computed WTCSMoM and WTCSrange for 1,000 random combinations of N high-TAS signatures for values of N between 3 and 9. For a perturbagen to be considered as giving a single signature, we required that its WTCSMoM be greater than 95% and its WTCSrange be less than 95% of its size-matched null.
