ToxDL 2.0: Protein toxicity prediction using a pretrained language model and graph neural networks

In this study, we present ToxDL 2.0, a novel multimodal deep learning model for protein toxicity prediction that integrates both evolutionary and structural information derived from a pretrained language model and AlphaFold2. ToxDL 2.0 consists of three key modules: (1) a Graph Convolutional Network (GCN) module for generating protein graph embeddings based on AlphaFold2-predicted structures, (2) a domain embedding module for capturing protein domain representations, and (3) a dense module that combines these embeddings to predict the toxicity. After constructing a comprehensive toxicity benchmark dataset, we obtained experimental results on both an original non-redundant test set (comprising pre-2022 protein sequences) and an independent non-redundant test set (a holdout set of post-2022 protein sequences), demonstrating that ToxDL 2.0 outperforms existing state-of-the-art methods. Additionally, we utilized Integrated Gradients to discover known toxic motifs associated with protein toxicity. A web server for ToxDL 2.0 is publicly available at www.csbio.sjtu.edu.cn/bioinf/ToxDL2/.