Prediction of reproductive and developmental toxicity using an attention and gate augmented graph convolutional network.
Journal:
Scientific reports
Published Date:
May 25, 2025
Abstract
Due to the diverse molecular structures of chemical compounds and their intricate biological pathways of toxicity, predicting their reproductive and developmental toxicity remains a challenge. Traditional Quantitative Structure-Activity Relationship models that rely on molecular descriptors have limitations in capturing the complexity of reproductive and developmental toxicity to achieve high predictive performance. In this study, we developed a descriptor-free deep learning model by constructing a Graph Convolutional Network designed with multi-head attention and gated skip-connections to predict reproductive and developmental toxicity. By integrating structural alerts directly related to toxicity into the model, we enabled more effective learning of toxicologically relevant substructures. We built a dataset of 4,514 diverse compounds, including both organic and inorganic substances. The model was trained and validated using stratified 5-fold cross-validation. It demonstrated excellent predictive performance, achieving an accuracy of 81.19% on the test set. To address the interpretability of the deep learning model, we identified subgraphs corresponding to known structural alerts, providing insights into the model's decision-making process. This study was conducted in accordance with the OECD principles for reliable Quantitative Structure-Activity Relationship modeling and contributes to the development of robust in silico models for toxicity prediction.
