Examples of CV-testing folds designed to have (A) all data points involving specific queries within 1-fold (points inside the purple box), (B) all data points involving specific targets within 1-fold (points inside the purple box) and (C) all data points involving the components of query compounds–target pairs within one testing fold (points inside the purple boxes). The data points covered by the blue boxes are omitted from both training and testing data during the CV round involving the purple boxed data as the testing set, and the remaining data points are used as the training set. Interacting pairs are shown in green while (putative) non-interacting pairs are shown in white (adapted from Pahikkala et al. [25]).