Study outline and new features used. (a) Study outline. Diverse features of gene pairs were computed and used to predict GIs using various classifiers. Performance was assessed by ten-fold cross-validation and the best combination of feature groups and classifier was selected. This combination was used to predict new GIs, which were subsequently tested against an independent E-MAP and negative interactions reported in the BioGrid database. In addition, we tested the correlation between the new GIs with functional similarity based on Gene Ontology. (b) Illustration of the GSG and GSG-MATRIX features. We were interested in predicting the GI between genes A and B. GSG features capture measured GIs between A and genes similar to B and vice versa. GSG-MATRIX features capture measured GIs between genes similar to A and genes similar to B.