摘要Computational approaches for predicting drug-target interactions(DTIs)are pivotal in advancing drug discovery.Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information.To comprehensively consider network information,we propose DHGT-DTI,a novel deep learning-based approach for DTI prediction.Specifically,we capture the local and global structural information of the network from both neighborhood and meta-path per-spectives.In the neighborhood perspective,we employ a heterogeneous graph neural network(HGNN),which extends Graph Sample and Aggregate(GraphSAGE)to handle diverse node and edge types,effectively learning local network structures.In the meta-path perspective,we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths,such as"drug-disease-drug",and use an attention mechanism to fuse information across multiple meta-paths.The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method.Furthermore,DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy.Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods.Additionally,case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.