Fig 3. Ensemble modeling segregates compound populations by hERG liability.

(a) Schematic of ensemble voting procedure. MLSMR compounds (left) are divided in 5 test folds (bottom), each receiving binary votes from an ensemble of hERG classifiers (center right) developed using balanced batches of the 80% training set not included in each test fold (top right). (b) The average vote of hERG blocker over all models in the ensemble is recorded as a hERG Blocker Score (hBS). Compounds with high hBS (red histogram bar) have consistent blocker classification, while those with low hBS (dark blue histogram bar) have consistent nonblocker classification. Compounds with intermediate hBS score are denoted by light blue histogram bars. (c) Distribution of hERG inhibition (10 μM) for compounds with High (>0.95), Intermediate (0.05<hBS<0.95) and Low (<0.05) hBS.