AI-driven neoantigen identification: a comprehensive review from somatic variant calling to T cell recognition

Abstract Background: Neoantigens—tumor-specific peptides generated by somatic mutations—are central targets of effective anticancer T cell immunity and underpin the clinical success of immune checkpoint blockade and personalized cancer vaccines. Advances in high-throughput sequencing, immunopeptidomics, and artificial intelligence (AI) have transformed neoantigen discovery from tailored experimental workflows into scalable, computational pipelines. However, accurately identifying the small subset of tumor mutations that yield processed, presented, and immunogenic epitopes remains a major bottleneck. Methods: This review summarizes how AI is reshaping neoantigen discovery,