DEPfold: RNA Secondary Structure Prediction as Dependency Parsing.

RNA secondary structure prediction is critical for understanding RNA functionbut remains challenging due to complex structural elements like pseudoknots andlimited training data. We introduce DEPfold, a novel deep learning approach thatre-frames RNA secondary structure prediction as a dependency parsing problem.DEPfold presents three key innovations: (1) a biologically motivated transformation of RNA structures into labeled dependency trees, (2) a biaffine attentionmechanism for joint prediction of base pairings and their types, and (3) an optimaltree decoding algorithm that enforces valid RNA structural constraints. Unlike traditional energy-based methods, DEPfold learns directly from annotated data andleverages pretrained language models to predict RNA structure. We evaluate DEPfold on both within-family and cross-family RNA datasets, demonstrating significant performance improvements over existing methods. DEPfold shows strongperformance in cross-family generalization when trained on data augmented bytraditional energy-based models, outperforming existing methods on the bpRNAnew dataset. This demonstrates DEPfold’s ability to effectively learn structuralinformation beyond what traditional methods capture. Our approach bridges natural language processing (NLP) with RNA biology, providing a computationallyefficient and adaptable tool for advancing RNA structure prediction and analysis