GHF-ACL: A novel contrastive learning framework with multi-order graph structures for herb-disease association prediction

by Yunmeng Zhang, Xiuhong Wu, Qiutong Wang, Lin Shi, Meiling Liu, Guohua Wang

Predicting Herb, Disease Associations (HDA) is pivotal for modernizing Traditional Chinese Medicine (TCM); however, this is impeded by data heterogeneity and the complex, multi-component mechanisms of herbal medicines. Existing drug, disease prediction models often struggle to capture high-order structural patterns and resolve semantic inconsistencies intrinsic to herbs. To overcome these limitations, we present HData, a standardized benchmark dataset that integrates herbal medicinal properties, chemical compositions, and disease associations. We further propose GHF-ACL, a novel multi-order graph contrastive learning framework designed for HDA prediction. Specifically, GHF-ACL explicitly models low-order functional similarities via a herb, disease similarity graph while capturing high-order component interactions through a herb, chemical hypergraph. Furthermore, an adaptive gating-guided structural interaction module aligns heterogeneous graph representations into a unified latent space, and hierarchical contrastive learning enforces consistency across structural views. Extensive experiments on five datasets demonstrate that GHF-ACL achieves superior or competitive performance over six state-of-the-art models across most metrics, with significant improvements over the best-performing baseline model in AUPR (+4.8% on LRSSL, + 3.81% on Cdata), F1 score, and Recall. These results underscore the model’s superior capability in detecting true positive associations within imbalanced biomedical data. By synergizing multi-view graph modeling, semantic fusion, and contrastive regularization, this work establishes a unified framework for HDA prediction, offering valuable insights for computational TCM and data-driven drug discovery.