KGM4DTI: A Depression Knowledge Graph-Driven Multi-semantic Multi-view Computational Framework for Drug-Target Interaction Prediction
Tian Xu, Peifu Han, Xue Li, Hongzhen Ding, Wei He, Fengrui Jing, Shuang Wang, Xun Wang, Tao Song · 2024
Depression is a prevalent global mental health issue that significantly impacts both individuals and societies. Current methods often overlook the heterogeneity of depressive symptoms and fail to fully leverage available data, underscoring the need for more advanced computational methods DTI prediction. This paper introduces KGM4DTI, a multi-semantic, multi-view, and multi-level meta-path Transformer framework that integrates Transformer and GNN. KGM4DTI effectively captures both global semantic and local structural information between interaction pairs within a depression knowledge graph (DepKG), which comprises 2,258 drugs, 3,360 proteins, 6 subtypes of depression, 196 phenotypes, and 238 pathways. Comparative experiments have demonstrated that KGM4DTI significantly outperforms existing state-of-the-art methods, achieving an AUROC of 99.72 and an AUPR of 99.76. The robustness of framework is further confirmed through extensive ablation studies, which highlight the crucial role of integrating both global and local information. These results underscore the potential of KGM4DTI in accurately predicting DTI. This approach has promising implications for drug discovery, particularly in developing effective treatments for depression, and could extend its applicability to broader mental health disorders. The data and code are available at https://github.com/Tianxyuu/KGM4DTI/.