To define AD in this study, we adopted the maximum value of Tanimoto similarity (MTS) for the training data, which is very simple but one of the most commonly used methods . At a reliability level ρ, a molecule is included in the AD of a prediction model if the highest value of Tanimoto similarities between the molecule and the ones in the training data of the model exceeds ρ. The spread size of an AD varies with the reliability level ρ.