Identification of non-canonical peptides with moPepGen

Nat Biotechnol. 2025 Jun 16. doi: 10.1038/s41587-025-02701-0. Online ahead of print.

Abstract

Proteogenomics is limited by the challenge of modeling the complexities of gene expression. We create moPepGen, a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. moPepGen works with multiple technologies, in multiple species and on all types of genetic and transcriptomic data. In human cancer proteomes, it enumerates previously unobservable noncanonical peptides arising from germline and somatic genomic variants, noncoding open reading frames, RNA fusions and RNA circularization.