{"doi":"10.1101/2020.02.12.945840","title":"Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer","abstract":"Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression. To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples, developed a sensitive analytic approach for hierarchical ORF prediction, and constructed a high-confidence database of translated nuORFs across tissues. Peptides from 3,555 unique translated nuORFs were presented on MHC I, based on analysis of an extensive dataset of MHC I-bound peptides detected by mass spectrometry, with >20-fold more nuORF peptides detected in the MHC I immunopeptidomes compared to whole proteomes. We further detected somatic mutations in nuORFs of cancer samples and identified nuORFs with tumor-specific translation in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs thus expand the pool of MHC I-presented, tumor-specific peptides, targetable by immunotherapies.","journal":null,"year":2020,"id":7582,"datarank":1.6732588098444916,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":1.0989626003711273,"self_endowment_contribution":0.5742962094733643,"citer_contribution":1.0989626003711273,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":39,"citers_with_citation_signal":35,"citers_with_endowment":35,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0505,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-02-13","fair_score":55.0,"fair_percentile":78.9,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7645,"name":"Travis Law","orcid":"0000-0002-7399-3299","position":1,"is_corresponding":false},{"id":2216,"name":"Karl R. 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