HGTRDA: Enhancing Prediction of ncRNA-Mediated Drug Resistance with Hypergraph Transformer

Exploring the intricate connections between non-coding RNAs (ncRNAs) and drug resistance is crucial for understanding the molecular mechanisms behind drug resistance, identifying novel drug development targets, and uncovering key biomarkers to optimize therapeutic strategies. Traditional biological assays face significant challenges, including high costs and lengthy timelines, prompting the need for advanced computational methods to predict ncRNA-drug resistance associations. In this study, we introduce HGTRDA, a novel computational framework designed to predict potential associations between ncRNAs and drug resistance. HGTRDA leverages LightGCN to generate node representations that capture topological information from the surrounding node neighborhood. These representations are then dynamically optimized using a global hypergraph transformer to model the relationships between ncRNAs and drug resistance. To enhance the quality of the learned embeddings, HGTRDA employs self-supervised learning to fine-tune topology-aware embeddings, reducing the impact of noise and improving representation quality. The final association scores between ncRNAs and drugs are computed using an inner product method. Empirical evaluations on the ncRNADrug database demonstrate that HGTRDA outperforms six contemporary state-of-the-art methods in predicting ncRNA-drug resistance associations. Furthermore, case studies illustrate the practical utility of HGTRDA as a predictive tool in real-world scenarios. The code and dataset for HGTRDA are freely available at https://github.com/one-melon/HGTRDA.