Evidence map›Paper›PMID 34663921›Full record

ArticleNature biotechnology2022

Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer.

Tamara Ouspenskaia, Travis Law, Karl R Clauser, Susan Klaeger, Siranush Sarkizova, François Aguet, Bo Li, Elena Christian, Binyamin A Knisbacher, Phuong M Le and 19 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
197citing papers in PubMed, 1 pooled it
18.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

197 citing papers in PubMed, 1 synthesis or guideline pooled it, 285 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Recoding by NNature communications · 2026
    Article
  6. Review
  7. Determining the dark proteome.Nature chemical biology · 2026
    Article
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137 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 5 institutions in 1 country.

Tamara Ouspenskaia *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5462-7103
Travis Law *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7399-3299
Karl R Clauser *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Susan Klaeger *Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0074-5163
Siranush SarkizovaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
François AguetBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9414-300X
Bo LiKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0668-1620
Elena ChristianHarvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5593-0155
Binyamin A KnisbacherBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4962-9956
Phuong M LeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Christina R HartiganBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hasmik KeshishianBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Annie ApffelBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2209-3944
Giacomo OliveiraDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7435-5603
Wandi ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sarah ChenPhillips Academy, Andover, MA, USA.
Yuen Ting ChowHarvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9483-7324
Zhe JiDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1809-8099
Irwin JungreisBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3197-5367
Sachet A ShuklaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Sune JustesenImmunitrack, Copenhagen, Denmark.
Pavan BachireddyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Manolis KellisBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7113-9630
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0936-0753
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2349-2656
Derin B KeskinBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8496-6181
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Catherine J WuBroad Institute of MIT and Harvard, Cambridge, MA, USA. cwu@partners.org.ORCID http://orcid.org/0000-0002-3348-5054
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA. aviv.regev.sc@gmail.com.ORCID http://orcid.org/0000-0003-3293-3158
Broad Institute · USDana-Farber Cancer Institute · USHarvard University Press · USNorthwestern University · USPhillips Academy · US

Funding

Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4M
GENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3M
ProteomicsP01CA206978 · NCI · DANA-FARBER CANCER INST · PI DAVIDS, MATTHEW S · 2016 to 2025
$17.0M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Personal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6M
MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0M
Center of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4M
Integrated high throughput proteogenomic data analysis center for CPTACU24CA210979 · NCI · BROAD INSTITUTE, INC. · PI BIRGER, CHET, GETZ, GAD A · 2016 to 2020
$4.4M
Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsR01HG004037 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS · 2007 to 2015
$3.9M
Cancer Immunology Training GrantT32CA207021 · NCI · DANA-FARBER CANCER INST · PI WUCHERPFENNIG, KAI W · 2016 to 2020
$2.4M
Characterizing functional translation in putative 'noncoding' regions of a genome: Admin SupplR35GM138192 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI JI, ZHE · 2020 to 2024
$2.1M
Post-transplant vaccines to enhance graft-versus-leukemia responsesR01HL103532 · NHLBI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2010 to 2013
$1.7M
NCI NIH HHS K99 CA207865NCI NIH HHS P01 CA206978NCI NIH HHS P50 CA101942NCI NIH HHS R00 CA207865NCI NIH HHS R01 CA155010NCI NIH HHS R21 CA216772NCI NIH HHS R50 CA211482NCI NIH HHS T32 CA207021NCI NIH HHS U01 CA214125NCI NIH HHS U24 CA210979NCI NIH HHS U24 CA210986NHGRI NIH HHS R01 HG004037NHGRI NIH HHS T32 HG002295NHGRI NIH HHS U41 HG007234NHLBI NIH HHS R01 HL103532NIGMS NIH HHS R35 GM138192
6 · The paper itself

Abstract

Tumor-associated epitopes presented on MHC-I that can activate the immune system against cancer cells are typically identified from annotated protein-coding regions of the genome, but whether peptides originating from novel or unannotated open reading frames (nuORFs) can contribute to antitumor immune responses remains unclear. Here we show that peptides originating from nuORFs detected by ribosome profiling of malignant and healthy samples can be displayed on MHC-I of cancer cells, acting as additional sources of cancer antigens. We constructed a high-confidence database of translated nuORFs across tissues (nuORFdb) and used it to detect 3,555 translated nuORFs from MHC-I immunopeptidome mass spectrometry analysis, including peptides that result from somatic mutations in nuORFs of cancer samples as well as tumor-specific nuORFs translated in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs are an unexplored pool of MHC-I-presented, tumor-specific peptides with potential as immunotherapy targets.

Indexed as

ImmunotherapyMelanomaAntigens, NeoplasmHistocompatibility Antigens Class IHumansMass SpectrometryPeptidesAntigens, NeoplasmHistocompatibility Antigens Class IPeptides

Identifiers

PMID34663921
PMCPMC10198624
OpenAlexW3205324211

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.