Evidence map›Paper›PMID 26631509›Full record

ArticleMolecular & cellular proteomics : MCP2016

An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer.

Kelly V Ruggles, Zuojian Tang, Xuya Wang, Himanshu Grover, Manor Askenazi, Jennifer Teubl, Song Cao, Michael D McLellan, Karl R Clauser, David L Tabb and 28 more

Abstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
–field-weighted citation impact
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

64 citing papers in PubMed.

  1. Article
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  6. Identification of non-canonical peptides with moPepGen.bioRxiv : the preprint server for biology · 2025
    Article
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4 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

38 authors.

Kelly V RugglesFrom the ‡New York University School of Medicine, New York, NY;
Zuojian TangFrom the ‡New York University School of Medicine, New York, NY;
Xuya WangFrom the ‡New York University School of Medicine, New York, NY;
Himanshu GroverFrom the ‡New York University School of Medicine, New York, NY;
Manor Askenazi§Biomedical Hosting, LLC, Arlington, MA;
Jennifer TeublFrom the ‡New York University School of Medicine, New York, NY;
Song Cao¶Washington University in St. Louis, St. Louis, MO;
Michael D McLellan¶Washington University in St. Louis, St. Louis, MO;
Karl R Clauser‖Broad Institute of Harvard and MIT, Cambridge, MA;
David L Tabb**Vanderbilt University School of Medicine, Nashville, TN;
Philipp Mertins‖Broad Institute of Harvard and MIT, Cambridge, MA;
Robbert Slebos**Vanderbilt University School of Medicine, Nashville, TN;
Petra Erdmann-Gilmore¶Washington University in St. Louis, St. Louis, MO;
Shunqiang Li¶Washington University in St. Louis, St. Louis, MO;
Harsha P Gunawardena‡‡Universtiy of North Carolina School of Medicine, Chapel Hill, NC;
Ling Xie‡‡Universtiy of North Carolina School of Medicine, Chapel Hill, NC;
Tao Liu§§Pacific Northwest National Laboratory, Richland, WA;
Jian-Ying Zhou¶¶Johns Hopkins University, Baltimore, MD;
Shisheng Sun¶¶Johns Hopkins University, Baltimore, MD;
Katherine A Hoadley‡‡Universtiy of North Carolina School of Medicine, Chapel Hill, NC;
Charles M Perou‡‡Universtiy of North Carolina School of Medicine, Chapel Hill, NC;
Xian Chen‡‡Universtiy of North Carolina School of Medicine, Chapel Hill, NC;
Sherri R Davies¶Washington University in St. Louis, St. Louis, MO;
Christopher A Maher¶Washington University in St. Louis, St. Louis, MO;
Christopher R Kinsinger‖‖Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD.
Karen D Rodland§§Pacific Northwest National Laboratory, Richland, WA;
Hui Zhang¶¶Johns Hopkins University, Baltimore, MD;
Zhen Zhang¶¶Johns Hopkins University, Baltimore, MD;
Li Ding¶Washington University in St. Louis, St. Louis, MO;
R Reid Townsend¶Washington University in St. Louis, St. Louis, MO;
Henry Rodriguez‖‖Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD.
Daniel Chan¶¶Johns Hopkins University, Baltimore, MD;
Richard D Smith§§Pacific Northwest National Laboratory, Richland, WA;
Daniel C Liebler**Vanderbilt University School of Medicine, Nashville, TN;
Steven A Carr‖Broad Institute of Harvard and MIT, Cambridge, MA;
Samuel Payne§§Pacific Northwest National Laboratory, Richland, WA; Samuel.Payne@pnnl.gov mellis@dom.wustl.edu david@fenyolab.org.
Matthew J Ellis¶Washington University in St. Louis, St. Louis, MO; Samuel.Payne@pnnl.gov mellis@dom.wustl.edu david@fenyolab.org.
David FenyőFrom the ‡New York University School of Medicine, New York, NY; Samuel.Payne@pnnl.gov mellis@dom.wustl.edu david@fenyolab.org.

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KATHERINE A. HOADLEY · 1992 to 2026
$59.3M
Proteo-genomic Discovery, Prioritization and Verification of Cancer BiomarkersU24CA160034 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, PAULOVICH, AMANDA G · 2011 to 2016
$16.2M
PNNL Clinical Proteome Characterization CenterU24CA160019 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI RODLAND, KARIN D, SMITH, RICHARD D · 2011 to 2016
$15.7M
Vanderbilt Proteome Characterization CenterU24CA159988 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LIEBLER, DANIEL C · 2011 to 2016
$13.9M
Cancer Proteome Center at Washington Univ, Univ of North Carolina & Boise StateU24CA160035 · NCI · WASHINGTON UNIVERSITY · PI CHEN, XIAN, ELLIS, MATTHEW J · 2011 to 2016
$11.8M
Proteome Characterization Center: A Genoproteomics Pipeline for Cance ResearchU24CA160036 · NCI · JOHNS HOPKINS UNIVERSITY · PI CHAN, DANIEL WANYUI, ZHANG, HUI · 2011 to 2016
$10.7M
Training program in Molecular BiophysicsT32GM088118 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI STOKES, DAVID L. · 2010 to 2019
$1.8M
NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA058223NCI NIH HHS U24 CA159988NCI NIH HHS U24CA159988NCI NIH HHS U24 CA160019NCI NIH HHS U24CA160019NCI NIH HHS U24 CA160034NCI NIH HHS U24CA160034NCI NIH HHS U24 CA160035NCI NIH HHS U24CA160035NCI NIH HHS U24 CA160036NCI NIH HHS U24CA160036NIGMS NIH HHS T32 GM088118
6 · The paper itself

Abstract

Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (<0.1%). Peptides mapping to DNA-detected SNVs without a detectable mRNA transcript were also observed, suggesting that transcriptome coverage was incomplete (∼80%). In contrast to germline variants, somatic variants were less likely to be detected at the peptide level in the basal-like tumor than in the luminal tumor, raising the possibility of differential translation or protein degradation effects. In conclusion, this large-scale proteogenomic integration allowed us to determine the degree to which mutations are translated and identify gaps in sequence coverage, thereby benchmarking current technology and progress toward whole cancer proteome and transcriptome analysis.

Indexed as

Alternative SplicingMutationAnimalsComputational BiologyDatabases, GeneticFemaleGenomeHumansMammary Neoplasms, ExperimentalMicePolymorphism, Single NucleotideProteomicsSequence Analysis, DNASequence Analysis, RNATandem Mass SpectrometryTranscriptome

Identifiers

PMID26631509
PMCPMC4813688

What OpenQuestion holds

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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.