Evidence map›Paper›PMID 25987412›Full record

ArticleMolecular & cellular proteomics : MCP2015

Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry Enables Multiplex, Quantitative Pharmacodynamic Studies of Phospho-Signaling.

Jeffrey R Whiteaker, Lei Zhao, Ping Yan, Richard G Ivey, Uliana J Voytovich, Heather D Moore, Chenwei Lin, Amanda G Paulovich

Abstract 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. An Introduction to Advanced Targeted Acquisition Methods.Molecular & cellular proteomics : MCP · 2021
    Review
  11. Clinical potential of mass spectrometry-based proteogenomics.Nature reviews. Clinical oncology · 2019
    Review
  12. Review
  13. Article
  14. Identification of Novel Physiological Substrates ofMolecular & cellular proteomics : MCP · 2018
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
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

8 authors.

Jeffrey R WhiteakerFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.ORCID http://orcid.org/0000-0001-5042-8580
Lei ZhaoFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Ping YanFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Richard G IveyFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Uliana J VoytovichFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Heather D MooreFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Chenwei LinFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109.
Amanda G PaulovichFrom the ‡Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, Washington 98109 apaulovi@fredhutch.org.ORCID http://orcid.org/0000-0001-6532-6499

Funding

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
Targeted immunotherapy of breast cancer with central memory T cellsP50CA138293 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PORTER, PEGGY L. · 2010 to 2014
$11.0M
NCI NIH HHS P50 CA138293NCI NIH HHS P50CA138293NCI NIH HHS U24 CA160034NCI NIH HHS U24CA160034
6 · The paper itself

Abstract

In most cell signaling experiments, analytes are measured one Western blot lane at a time in a semiquantitative and often poorly specific manner, limiting our understanding of network biology and hindering the translation of novel therapeutics and diagnostics. We show the feasibility of using multiplex immuno-MRM for phospho-pharmacodynamic measurements, establishing the potential for rapid and precise quantification of cell signaling networks. A 69-plex immuno-MRM assay targeting the DNA damage response network was developed and characterized by response curves and determinations of intra- and inter-assay repeatability. The linear range was ≥ 3 orders of magnitude, the median limit of quantification was 2.0 fmol/mg, the median intra-assay variability was 10% CV, and the median interassay variability was 16% CV. The assay was applied in proof-of-concept studies to immortalized and primary human cells and surgically excised cancer tissues to quantify exposure-response relationships and the effects of a genomic variant (ATM kinase mutation) or pharmacologic (kinase) inhibitor. The study shows the utility of multiplex immuno-MRM for simultaneous quantification of phosphorylated and nonmodified peptides, showing feasibility for development of targeted assay panels to cell signaling networks.

Indexed as

Signal TransductionAdultBiological AssayCell LineChromatography, AffinityGenetic VariationHumansIndicators and ReagentsMass SpectrometryNeoplasmsPhosphopeptidesPhosphorylationProtein Kinase InhibitorsIndicators and ReagentsPhosphopeptidesProtein Kinase Inhibitors

Identifiers

PMID25987412
PMCPMC4528251

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.