A pre-trained language model-based cross-modal fusion framework for predicting miRNA-drug resistance and sensitivity associations.

Abstract

MicroRNAs (miRNAs) are pivotal regulators of drug resistance and sensitivity in cancer cells, functioning as tumor suppressors or oncogenes that modulate the cellular response to anticancer drugs. While experimental identification of miRNA-mediated drug resistance and sensitivity is both costly and laborious, computational methods present a promising alternative. Recent advances in pre-trained language models (PLMs) offer new opportunities to leverage large-scale unlabeled biomolecular data for enhanced relationship prediction. In this study, we introduce PLMF-MDA, a PLM-based cross-modal fusion model designed to predict miRNA-drug resistance (MDR) and miRNA-drug sensitivity (MDS) associations. PLMF-MDA integrates miRNA and drug multimodal embeddings derived from PLMs and intrinsic feature extractors, and employs a cross-modal attention fusion module to adaptively capture key interactions between modalities. To evaluate the performance of the approach, we manually constructed two benchmark datasets. Experimental results demonstrate that the PLMF-MDA achieves superior prediction performance. Furthermore, case studies on anticancer drug docetaxel and gefitinib demonstrate its potential in discovering novel MDR (MDS) associations. All data and source code are available on GitHub: https://github.com/sheng-n/PLMF-MDA.