EAAI Journal 2026 Journal Article
A multi-view collaborative heterogeneous graph neural network with semantic- and relation-aware for drug-disease association prediction
- Jinzhou Wu
- Donglin He
- Xin Li
- Rui Wang
- Yujuan Zhang
Drug repositioning (DR) is crucial for accelerating drug development and reducing costs; computational methods offer efficient alternatives to costly traditional methods. However, existing methods rely on static linear operations for integrating multi-source similarity networks, causing noise accumulation and redundancy. Additionally, meta-path aggregation often fails to dynamically balance intra-path interactions and cross-path heterogeneity, limiting multi-granularity information fusion. To address these, we propose a Multi-view Collaborative Heterogeneous Graph Neural Network with Semantic and Relation-Aware (MSRHGNN) for Drug-Disease Association (DDA) prediction. MSRHGNN jointly encodes similarity and heterogeneous biological network features. It first uses an adaptive dynamic fusion mechanism to integrate multi-source similarity data, leveraging a Graph Transformer to capture richer structural features. Second, within the heterogeneous biological network, the low-order relational view aggregates first-order neighborhood information to capture local topology, while the high-order relational view designs a dual attention collaborative aggregation mechanism: node-level attention driven by central anchor points highlights key interactions within paths, and semantic and relation-aware mechanisms at the cross-path level quantify the consistency within paths and heterogeneity between paths, achieving complementary dynamic fusion. Additionally, MSRHGNN aligns node- and graph-level representations through a multi-view contrastive learning strategy and employs a multi-task balance strategy to alleviate gradient conflicts between the main and auxiliary tasks. Experimental results demonstrate that our method outperforms other baseline models across multiple evaluation metrics on several public datasets, with its stability and robustness validated under cold-start, imbalanced, and noisy conditions. Furthermore, case studies on specific diseases and molecular docking experiments highlight its potential value in practical drug discovery.