Evidence map›Paper›PMID 26076430›Full record

ArticleNature biotechnology2015

A mass-tolerant database search identifies a large proportion of unassigned spectra in shotgun proteomics as modified peptides.

Joel M Chick, Deepak Kolippakkam, David P Nusinow, Bo Zhai, Ramin Rad, Edward L Huttlin, Steven P Gygi

Erratum issuedAbstract read
In one paragraph

Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 197 papers.

0numbers the graph read from it
0cells of the map it votes in
197citing 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

197 citing papers in PubMed.

  1. PSMatch: An R/Bioconductor Package to Explore Proteomics Identification Data.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
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  3. Review
  4. Estimating protein isoform abundances with [Formula: see text].Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
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  7. Article
  8. Review
  9. Article
  10. CLASPP: A unified model for predicting post-translational modifications.bioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Generalizable Direct Protein Sequencing With InstaNexus.Molecular & cellular proteomics : MCP · 2026
    Article
  17. Article
  18. Article
  19. Review
  20. Article

137 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Joel M ChickDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
Deepak KolippakkamDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
David P NusinowDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000000278195261
Bo ZhaiDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000000251203241
Ramin RadDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
Edward L HuttlinDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.

Funding

New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
New Technologies for Quantitative Phosphorylation AnalysisR01HG003456 · NHGRI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2005 to 2011
$2.7M
NHGRI NIH HHS HG3456NHGRI NIH HHS R01 HG003456NIGMS NIH HHS GM67945NIGMS NIH HHS R01 GM067945
6 · The paper itself

Abstract

Fewer than half of all tandem mass spectrometry (MS/MS) spectra acquired in shotgun proteomics experiments are typically matched to a peptide with high confidence. Here we determine the identity of unassigned peptides using an ultra-tolerant Sequest database search that allows peptide matching even with modifications of unknown masses up to ± 500 Da. In a proteome-wide data set on HEK293 cells (9,513 proteins and 396,736 peptides), this approach matched an additional 184,000 modified peptides, which were linked to biological and chemical modifications representing 523 distinct mass bins, including phosphorylation, glycosylation and methylation. We localized all unknown modification masses to specific regions within a peptide. Known modifications were assigned to the correct amino acids with frequencies >90%. We conclude that at least one-third of unassigned spectra arise from peptides with substoichiometric modifications.

Indexed as

Databases, ProteinTandem Mass SpectrometryAmino Acid SequenceHEK293 CellsHumansMolecular Sequence DataPeptide MappingPeptidesProteinsProteomicsPeptidesProteins

Identifiers

PMID26076430
PMCPMC4515955

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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.