The models in Equation 1 that describe the predicted ratio of actives for each balancing strategy are summarized in Tables S8-S9 of the Supporting Information. For semi_resampling and resampling_before_clustering (Table ), the original actives ratio in the test set had a positive, significant effect on the predicted actives ratio (β = 0.945 and 0.784, both p < 10 -16 ). However, the original actives ratio of the training set showed no evidence of affecting the predicted ratio (β = 0.197 and -0.446, p = 0.73 and 0.31). Conversely, for the no_resampling strategy (Table ), both the original training (β = 8.312, p < 10 -16 ) and test ratios (β = 1.102, p = 2.6 • 10 -9 ) had positive, significant effects on the predicted actives ratio. In the three models, the number of interactions per protein had a significant, negative effect (β = -0.391, -0.396 and -1.24, all p < 10 -16 ), and some of the folds entailed significant variations of the predicted ratio.