SeqDA-HLA: Language Model and Dual Attention-Based Network to Predict Peptide-HLA Class I Binding

Abstract

Accurate prediction of peptide-HLA class I binding is crucial for immunotherapy and vaccine development, but existing methods often struggle to capture the intricate biological relationships between peptides and diverse HLA alleles. Here, we introduce SeqDA-HLA, a pan-specific prediction model that combines language model-based embeddings (ELMo) with a dual attention mechanism-self-aligned cross-attention and self-attention-to capture rich contextual features and pairwise interactions. Evaluations against 14 state-of-the-art methods on multiple benchmark datasets demonstrate that SeqDA-HLA consistently outperforms competing approaches, achieving an AUC value up to 0.9856 and accuracy as high as 0.9408. Notably, SeqDA-HLA maintains robust performance across peptide lengths (8-14) and HLA alleles, showcasing its generalizability. Beyond predictive accuracy, SeqDA-HLA offers interpretability by highlighting essential anchor residues and revealing key binding motifs, thereby aligning with experimentally validated biological insights. As a further demonstration of practical impact, we fine-tune SeqDA-HLA on an Influenza virus dataset, successfully predicting binding changes induced by single amino acid mutations. Overall, SeqDA-HLA serves as a powerful and interpretable tool for peptide-HLA binding prediction, with potential applications in epitope-based vaccine design and precision immunotherapy.