Annotating protein functions via fusing multiple biological modalities

Understanding the function of proteins is of great significance for revealing disease pathogenesis and discovering new targets. Benefiting from the explosive growth of the protein universal, deep learning has been applied to accelerate the protein annotation cycle from different biological modalities. However, most existing deep learning-based methods not only fail to effectively fuse different biological modalities, resulting in low-quality protein representations, but also suffer from the convergence of suboptimal solution caused by sparse label representations. Aiming at the above issue, we propose a multiprocedural approach for fusing heterogeneous biological modalities and annotating protein functions, i.e., MIF2GO (Multimodal Information Fusion to infer Gene Ontology terms), which sequentially fuses up to six biological modalities ranging from different biological levels in three steps, thus leading to powerful protein representations. Evaluation results on seven benchmark datasets show that the proposed method not only considerably outperforms state-of-the-art performance, but also demonstrates great robustness and generalizability across species. Besides, we also present biological insights into the associations between those modalities and protein functions. This research provides a robust framework for integrating multimodal biological data, offering a scalable solution for protein function annotation, ultimately facilitating advancements in precision medicine and the discovery of novel therapeutic strategies.