TransHLA: A Hybrid Transformer Model for HLA-Presented Epitope Detection

Abstract

BackgroundPrecise prediction of epitope presentation on human leukocyte antigen (HLA) molecules is crucial for advancing vaccine development and immunotherapy. Conventional HLA-peptide binding affinity prediction tools often focus on specific alleles and lack a universal approach for comprehensive HLA site analysis. This limitation hinders efficient filtering of invalid peptide segments. ResultsWe introduce TransHLA, a pioneering tool designed for epitope prediction across all HLA alleles, integrating Transformer and Residue CNN architectures. TransHLA utilizes the ESM2 large language model for sequence and structure embeddings, achieving high predictive accuracy. For HLA class I, it reaches an accuracy of 84.72% and an AUC of 91.95% on IEDB test data. For HLA class II, it achieves 79.94% accuracy and an AUC of 88.14%. Our case studies using datasets like CEDAR and VDJdb demonstrate that TransHLA surpasses existing models in specificity and sensitivity for identifying immunogenic epitopes and neoepitopes. ConclusionsTransHLA significantly enhances vaccine design and immunotherapy by efficiently identifying broadly reactive peptides. Our resources, including data and code, are publicly accessible at https://github.com/SkywalkerLuke/TransHLA Key PointsO_LIWe developed TransHLA, a deep learning tool for predicting epitopes across all HLA alleles using Transformer and Residue CNN architectures. C_LIO_LIThe model uses ESM2 embeddings to improve predictive accuracy and efficiency. C_LIO_LITransHLA shows superior specificity and sensitivity in identifying immunogenic epitopes and neoepitopes compared to existing models. C_LIO_LIOur approach offers potential advancements in vaccine design and immunotherapy through enhanced peptide analysis. C_LI