DeepLigand: accurate prediction of MHC class I ligands using peptide embedding

Abstract

Motivation: The computational modeling of peptide display by class I major histocompatibility complexes (MHCs) is essential for peptide-based therapeutics design. Existing computational methods for peptide-display focus on modeling the peptide-MHC-binding affinity. However, such models are not able to characterize the sequence features for the other cellular processes in the peptide display pathway that determines MHC ligand selection. Results: We introduce a semi-supervised model, DeepLigand that outperforms the state-of-the-art models in MHC Class I ligand prediction. DeepLigand combines a peptide language model and peptide binding affinity prediction to score MHC class I peptide presentation. The peptide language model characterizes sequence features that correspond to secondary factors in MHC ligand selection other than binding affinity. The peptide embedding is learned by pre-training on natural ligands, and can discriminate between ligands and non-ligands in the absence of binding affinity prediction. Although conventional affinity-based models fail to classify peptides with moderate affinities, DeepLigand discriminates ligands from non-ligands with consistently high accuracy.