Flexible machine learning prediction of antigen presentation for rare and common HLA-I alleles

Summary The recent increase of immunopeptidomic data, obtained by mass spectrometry or binding assays, opens unprecedented possibilities for investigating endogenous antigen presentation by the highly polymorphic human leukocyte antigen class I (HLA-I) protein. We introduce a flexible and easily interpretable peptide presentation prediction method, RBM-MHC. We validate its performance as a predictor of cancer neoantigens and viral epitopes and we use it to reconstruct peptide motifs presented on specific HLA-I molecules. By benchmarking RBM-MHC performance on a wide range of HLA-I alleles, we show its importance to improve prediction accuracy for rarer alleles.