Tanimoto similarities for all molecules in our dataset. Then, we assigned to each molecule a similarity group containing all molecules with a Tanimoto similarity above a certain threshold (0.80). Next, we computed common subset thresholds considering not only true activity points but also activity points in the similarity groups. This is, for threshold calculation a non-existing activity point of molecule X in variant A was counted as existing if compound Y, similar to X, was tested in variant A.