CrypticProteinDB

Translated non-canonical proteins derived from noncoding regions or alternative open reading frames (ORFs) can contribute to critical and diverse cellular processes. In the context of cancer, they also represent an under-appreciated source of targets for cancer immunotherapy through their tumor-enriched expression or by harboring somatic mutations that produce neoantigens. Here, we introduce the largest integration and proteogenomic analysis of novel peptides to assess the prevalence of non-canonical ORFs (ncORFs) in more than 900 patient proteomes and 26 immunopeptidome datasets across 14 cancer types. The integrative proteogenomic analysis of whole-cell proteomes and immunopeptidomes revealed peptide support for a nonredundant set of 9760 upstream, downstream, and out-of-frame ncORFs in protein coding genes and 12811 in noncoding RNAs. Notably, 6486 ncORFs were derived from differentially expressed genes and 340 were ubiquitously translated across eight or more cancers.