BiBLDR: Bidirectional Behavior Learning for Drug Repositioning
1.BiBLDR reframes drug repositioning as a behavioral sequence prediction task, inspired by recommendation systems. Instead of modeling associations via graphs, it learns from interaction patterns between drugs and diseases, enabling stronger generalization—especially for new drugs.
2.The method constructs bidirectional behavioral sequences, representing both drug-to-disease and disease-to-drug associations. This dual perspective captures more complete interaction signals than unidirectional models.
3.BiBLDR is the first to apply Transformer architecture to drug repositioning using behavior sequences. The model leverages multi-head self-attention to extract complex semantic patterns in both drug and disease behavioral contexts.
4.A two-stage learning strategy is proposed: • Stage I builds latent prototype spaces for drugs and diseases using similarity data and Siamese networks. • Stage II uses these prototypes, enriched with explicit similarity information, as input to the Transformer to predict associations.
5.Similarity fusion plays a central role. BiBLDR integrates numerical similarity values directly into prototype features within behavioral sequences, enhancing contrast between similar and dissimilar entities.
6.The model introduces a logarithmic weighting scheme in behavioral sequences to emphasize positive associations during training, aiding contrastive learning and mitigating sparsity.
7.BiBLDR demonstrates state-of-the-art performance on three benchmark datasets (Gdataset, Cdataset, LRSSL), outperforming both classical and deep learning methods, including GCN-based approaches, in AUROC and AUPRC.
8.In cold-start scenarios, where novel drugs have no known associations, BiBLDR outperforms existing methods with a large margin (e.g., AUPRC of 0.6194 vs 0.3484), validating its ability to generalize beyond observed data.
9.BiBLDR maintains robustness under extreme data sparsity, thanks to the independent prototype construction stage, which does not rely on the association matrix’s density.
10.Ablation studies confirm the value of each design component: bidirectional modeling, prototype spaces, similarity fusion, and Transformer layers all significantly contribute to performance.
11.In real-world case studies on lung cancer and hypertension, BiBLDR achieved high hit rates (80%–90%) in top-ranked predictions. For unverified predictions, molecular docking experiments confirmed strong binding affinities.
12.In conclusion, BiBLDR offers a novel and effective direction for drug repositioning research, combining strengths of recommender systems, prototype learning, and attention-based modeling.
💻Code:
github.com/Renyeeah/BiBLDR
📜Paper:
arxiv.org/abs/2505.23861v1
#DrugRepositioning #Transformer #DeepLearning #BiomedicalAI #RecommendationSystem