Figure represents the ratio of predicted actives by protein and Table of the Supporting Information summarizes the percentage of proteins with all actives or inactives (ex-treme cases). They show that no_resampling strategy was inclined to predict everything as positives (71.6% of the time, compared to 3.5% for predicting all negatives). Resam-pling_before_clustering and semi_resampling alleviated the imbalance in the predictions, but still retained a spike of proteins where all the compounds were predicted as positives (23.4% and 29.1%) and negatives (5.5% and 4%). Resampling_after_clustering kept a wide and symmetric distribution of predicted actives, with only 1.2% predicted as all actives and 0% as all inactives. ), but since the training and the test ratio are also positively correlated (Figure ), the latter could be the one driving the predicted ratio of positives;