Adverse drug reaction (ADR) prediction is typically formulated as drug-ADR association learning on extremely sparse, positive-unlabeled matrices, which limits generalization and makes naive pseudolabel expansion prone to confirmation bias. Here, we propose DWPL-GCNMF, a structure-aware semisupervised framework that combines graph convolutional network (GCN)-based structural embeddings learned from a drug-protein knowledge graph with matrix factorization scoring and introduces a prediction-consistency-driven dynamic weighted pseudolabel learning strategy to expand training pairs while down-weighting unreliable pseudolabels; multiple base models are further fused to improve prediction stability. We evaluate DWPL-GCNMF on a DrugBank-derived benchmark (1,177 drugs × 4,247 ADRs; ∼2.6% observed associations) and an external SIDER benchmark (1,080 drugs × 5,579 ADRs; ∼2.3% observed associations) to assess robustness under different data sets and increased sparsity. DWPL-GCNMF consistently outperforms representative baselines, achieving AUPR/F1 of 0.6656/0.6194 on DrugBank and 0.6106/0.5816 on SIDER, while also improving top-K prioritization (e.g., Recall@15 up to 0.8078 and 0.8146, respectively), indicating that structure-aware representation learning with dynamically weighted pseudolabeling provides a robust approach for prioritizing potential ADRs under severe data sparsity.
Chen et al. (Fri,) studied this question.