NeuTox 2.0: A hybrid deep learning architecture for screening potential neurotoxicity of chemicals based on multimodal feature fusion.

Chemically induced neurotoxicity is a critical aspect of chemical safety assessment. Traditional and costly experimental methods call for the development of high-throughput virtual screening. However, the small datasets of neurotoxicity have limited the application of advanced deep learning techniques. The current study developed a hybrid deep learning architecture, NeuTox 2.0, through multimodal feature fusion for enhanced prediction accuracy and generalization ability. We incorporated transfer learning based on self-supervised learning, graph neural networks, and molecular fingerprints/descriptors. Four datasets were used to profile neurotoxicity; these were related to blood-brain barrier permeability, neuronal cytotoxicity, microelectrode array-based neural activity, and mammalian neurotoxicity. Comprehensive performance evaluations demonstrated that NeuTox 2.0 has relatively higher predictive capability across all statistical metrics. Specifically, NeuTox 2.0 exhibits remarkable performance in three of the four datasets. In the BBB dataset, although it does not outperform the PaDEL descriptor model, its performance closely approximates that of the top single-modal model. The ablation experiments indicated that NeuTox 2.0 can learn the deeper structural differences of molecules from various feature extractions and capture complex interactions and mapping relationships between various modalities, thereby improving performance for neurotoxicity prediction. Evaluations of anti-noise ability indicated that NeuTox 2.0 has excellent noise resistance relative to traditional machine learning. We applied the NeuTox 2.0 model to predict the neurotoxicity of 315,790 compounds in the REACH database. The results showed that 701 compounds exhibited potential neurotoxicity in the four neurotoxicity-related predictions. In conclusion, NeuTox 2.0 can be used as an efficient tool for early neurotoxicity screening of environmental chemicals.