To benchmark the predictive performance of AWESOM, we referred to the identical test set (a subset of the METAQSAR database) previously used for testing the established SOM predictor FAME 3. However, for model training, we were able to make use of an extended and refined training set (a subset of a new version of the METAQSAR database) as well as a refined data preprocessing pipeline (see Methods, section 2.2, and Supporting Information, section S.2, for details). To enable a fair, direct comparison of the two methods we retrained FAME 3 using the new, identical training set we employed for training AWESOM, and refer to this model as FAME 3R throughout the paper.