Construction of interpretable ensemble learning models for predicting bioaccumulation parameters of organic chemicals...

Accurate prediction of bioaccumulation parameters is essential for assessing exposure, hazards, and risks of chemicals. However, the majority of prediction models on bioaccumulation parameters are individual models based on a single algorithm and lack model interpretation, resulting in unsatisfactory prediction accuracy due to inherent constraints of the algorithm and weak interpretability. Ensemble learning (EL) that combine multiple algorithms, coupled with SHapley Additive exPlanation (SHAP) method, may overcome the limitations. Herein, EL models were constructed for three bioaccumulation parameters using datasets covering 2496 chemicals. The EL models demonstrated superior prediction accuracy compared to both individual models developed in this study and those from previous research, achieving a coefficient of determination of up to 0.861 on the validation sets. Applicability domains were characterized using a structure-activity landscape-based (abbreviated as AD_SAL) methodology. The optimal EL models, together with the AD_SAL, were successfully used to predict bioaccumulation parameters for 4374 chemicals included in the Inventory of Existing Chemical Substances of China. Model interpretation using the SHAP method offered insight into key features influencing bioaccumulation potential, including hydrophobicity, water solubility, polarizability, ionization potential, weight, and volume of molecules. Overall, the study provides data and models to support the sound management and risk assessment of chemicals.