Evidence map›Paper›PMID 26193884›Full record

ArticleMolecular & cellular proteomics : MCP2015

The Negative Mode Proteome with Activated Ion Negative Electron Transfer Dissociation (AI-NETD).

Nicholas M Riley, Matthew J P Rush, Christopher M Rose, Alicia L Richards, Nicholas W Kwiecien, Derek J Bailey, Alexander S Hebert, Michael S Westphall, Joshua J Coon

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Review
  3. Phosphorothioate RNA Analysis by NETD Tandem Mass Spectrometry.Molecular & cellular proteomics : MCP · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Dual Polarity Ion Confinement and Mobility Separations.Journal of the American Society for Mass Spectrometry · 2019
    Article
  16. Gas-Phase Hydrogen/Deuterium Scrambling in Negative-Ion Mode Tandem Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2019
    Article
  17. Review
  18. Review
  19. Replacing HChemical science · 2018
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Nicholas M RileyFrom the ‡Department of Chemistry, §Genome Center, and.
Matthew J P RushFrom the ‡Department of Chemistry, §Genome Center, and.
Christopher M RoseFrom the ‡Department of Chemistry, §Genome Center, and.
Alicia L RichardsFrom the ‡Department of Chemistry, §Genome Center, and.
Nicholas W KwiecienFrom the ‡Department of Chemistry, §Genome Center, and.
Derek J Bailey§Genome Center, and.
Alexander S Hebert§Genome Center, and.
Michael S Westphall§Genome Center, and.
Joshua J CoonFrom the ‡Department of Chemistry, §Genome Center, and ¶Department of Biomolecular Chemistry University of Wisconsin, Madison, Wisconsin, 53706 jcoon@chem.wisc.edu.
New York Genome Center · US

Funding

Institutional Training in the Genomic SciencesT32HG002760 · NHGRI · UNIVERSITY OF WISCONSIN-MADISON · PI Qiongshi Lu · 2003 to 2026
$17.7M
Chemistry-Biology Interface Training ProgramT32GM008505 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BLACKWELL, HELEN E. · 1993 to 2023
$9.8M
Sequential Ion/Ion Reactions for Large Peptide and Whole Protein CharacterizationR01GM080148 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI COON, JOSHUA J · 2007 to 2015
$3.0M
NHGRI NIH HHS 5T32HG002760NHGRI NIH HHS T32 HG002760NIGMS NIH HHS R01 GM080148NIGMS NIH HHS T32 GM008505NIGMS NIH HHS T32GM008505
6 · The paper itself

Abstract

The field of proteomics almost uniformly relies on peptide cation analysis, leading to an underrepresentation of acidic portions of proteomes, including relevant acidic posttranslational modifications. Despite the many benefits negative mode proteomics can offer, peptide anion analysis remains in its infancy due mainly to challenges with high-pH reversed-phase separations and a lack of robust fragmentation methods suitable for peptide anion characterization. Here, we report the first implementation of activated ion negative electron transfer dissociation (AI-NETD) on the chromatographic timescale, generating 7,601 unique peptide identifications from Saccharomyces cerevisiae in single-shot nLC-MS/MS analyses of tryptic peptides-a greater than 5-fold increase over previous results with NETD alone. These improvements translate to identification of 1,106 proteins, making this work the first negative mode study to identify more than 1,000 proteins in any system. We then compare the performance of AI-NETD for analysis of peptides generated by five proteases (trypsin, LysC, GluC, chymotrypsin, and AspN) for negative mode analyses, identifying as many as 5,356 peptides (1,045 proteins) with LysC and 4,213 peptides (857 proteins) with GluC in yeast-characterizing 1,359 proteins in total. Finally, we present the first deep-sequencing approach for negative mode proteomics, leveraging offline low-pH reversed-phase fractionation prior to online high-pH separations and peptide fragmentation with AI-NETD. With this platform, we identified 3,467 proteins in yeast with trypsin alone and characterized a total of 3,730 proteins using multiple proteases, or nearly 83% of the expressed yeast proteome. This work represents the most extensive negative mode proteomics study to date, establishing AI-NETD as a robust tool for large-scale peptide anion characterization and making the negative mode approach a more viable platform for future proteomic studies.

Indexed as

ProteomeChromatography, LiquidElectronsHydrogen-Ion ConcentrationProteomicsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTandem Mass SpectrometryProteomeSaccharomyces cerevisiae Proteins

Identifiers

PMID26193884
PMCPMC4597142
OpenAlexW1892358288

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.