HAGCN: Heterogeneous Attentive GCN for Gene-Disease Association

Kibeom Kim, Giltae Song

http://doi.org/10.5626/JOK.2025.52.2.161

Predicting gene-disease associations (GDAs) is essential for understanding molecular mechanisms, diagnosing disease, and targeting genes. Validating causal relationships between diseases and genes using experimental methods can be extremely costly and time-consuming. Deep learning, particularly graph neural networks, has shown great promise in this area. However, most models rely on single-source, homogeneous graphs. Another is the need for expert knowledge in manual definition of meta-paths to build multi-source heterogeneous graphs. Recognizing these challenges, the present study introduces the Heterogeneous Attentive Graph Convolution Network (HAGCN). HAGCN processes heterogeneous biological entity association graphs as input. We construct the input graphs using the biological association information from curated databases such as Gene Ontology, Disease Ontology, Human Phenotype Ontology, and TBGA. HAGCN learns the relationship heterogeneity between biological entities without meta-paths by using the attention mechanism. HAGCN achieved the best performance in AUC-ROC in a binary classification task to predict gene-disease association, and also achieved competitive performance in F1 score, MCC, and accuracy against baselines. We believe that HAGCN can accelerate the discovery of disease-associated genes and