Prediction Model of Aryl Hydrocarbon Receptor Activation by a Novel QSAR Approach, DeepSnap-Deep Learning

Molecules. 2020 Mar 13;25(6):1317. doi: 10.3390/molecules25061317.


The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that senses environmental exogenous and endogenous ligands or xenobiotic chemicals. In particular, exposure of the liver to environmental metabolism-disrupting chemicals contributes to the development and propagation of steatosis and hepatotoxicity. However, the mechanisms for AhR-induced hepatotoxicity and tumor propagation in the liver remain to be revealed, due to the wide variety of AhR ligands. Recently, quantitative structure-activity relationship (QSAR) analysis using deep neural network (DNN) has shown superior performance for the prediction of chemical compounds. Therefore, this study proposes a novel QSAR analysis using deep learning (DL), called the DeepSnap-DL method, to construct prediction models of chemical activation of AhR. Compared with conventional machine learning (ML) techniques, such as the random forest, XGBoost, LightGBM, and CatBoost, the proposed method achieves high-performance prediction of AhR activation. Thus, the DeepSnap-DL method may be considered a useful tool for achieving high-throughput in silico evaluation of AhR-induced hepatotoxicity.

Keywords: DeepSnap; QSAR; aryl hydrocarbon receptor; chemical structure; deep learning; machine learning.