Evidence map›Paper›PMID 34818016›Full record

ArticleJournal of proteome research2022

Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer's Disease.

Evan E Hubbard, Lilian R Heil, Gennifer E Merrihew, Jasmeer P Chhatwal, Martin R Farlow, Catriona A McLean, Bernardino Ghetti, Kathy L Newell, Matthew P Frosch, Randall J Bateman and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  5. Review
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  8. Article
  9. Unusually Rapid Isomerization of Aspartic Acid in Tau.bioRxiv : the preprint server for biology · 2024
    Article
  10. Review
  11. Localizing Isomerized Residue Sites in Peptides with Tandem Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024
    Article
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  13. Article
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  16. Review
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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

16 authors at 9 institutions in 2 countries.

Evan E HubbardDepartment of Chemistry, University of California, Riverside, California 92521, United States.
Lilian R HeilDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0002-9462-7327
Gennifer E MerrihewDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, United States.
Jasmeer P ChhatwalMassachusetts General Hospital, Department of Neurology, Harvard Medical School, 15 Parkman St, Suite 835, Boston Massachusetts 02114, United States.
Martin R FarlowDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
Catriona A McLeanDepartment of Anatomical Pathology, Alfred Health, Melbourne VIC 3004, Australia.
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
Kathy L NewellDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
Matthew P FroschC.S. Kubik Laboratory for Neuropathology, and Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, Missouri 63110, United States.
Eric B LarsonKaiser Permanente Washington Health Research Institute and Department of Medicine, University of Washington, Seattle, Washington 98195, United States.
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington 98195, United States.
Richard J PerrinDepartment of Pathology and Immunology, Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri 63110, United States.
Thomas J MontineDepartment of Pathology, Stanford University, Stanford, California 94305, United States.ORCID 0000-0002-1346-2728
Michael J MacCossDepartment of Genome Sciences, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0003-1853-0256
Ryan R JulianDepartment of Chemistry, University of California, Riverside, California 92521, United States.ORCID 0000-0003-1580-8355
University of Washington · USIndiana University School of MedicineUniversity of California, Riverside · USWashington University in St. Louis · USAlfred Health · AUHarvard University · USKaiser Permanente Washington Health Research Institute · USMassachusetts General Hospital · USStanford University · US

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
Furthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7M
Dominantly Inherited Alzheimer NetworkUF1AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2014 to 2017
$21.6M
Project 4: Novel reagent development to enable molecular characterizationU19AG065156 · NIA · UNIVERSITY OF WASHINGTON · PI TIAN, LU · 2020 to 2024
$15.9M
Imaging CoreU01AG032438 · NIA · WASHINGTON UNIVERSITY · PI XIONG, CHENGJIE · 2008 to 2009
$6.1M
Molecular Phenotyping in Alzheimer's DiseaseRF1AG053959 · NIA · STANFORD UNIVERSITY · PI LARSON, ERIC B, MACCOSS, MICHAEL · 2016 to 2017
$4.1M
Connecting long-lived protein isomerization to lysosomal failure in Alzheimer's diseaseR01AG066626 · NIA · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI JULIAN, RYAN ROY · 2020 to 2024
$2.8M
Complexity and Heterogeneity of Alzheimer diseaseR56AG061196 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 2019 to 2019
$654k
NIA NIH HHS P01 AG003991NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066509NIA NIH HHS R01 AG066626NIA NIH HHS R56 AG061196NIA NIH HHS RF1 AG053959NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG032438NIA NIH HHS U19 AG032438NIA NIH HHS U19 AG065156NIA NIH HHS UF1 AG032438
6 · The paper itself

Abstract

One of the potential benefits of using data-independent acquisition (DIA) proteomics protocols is that information not originally targeted by the study may be present and discovered by subsequent analysis. Herein, we reanalyzed DIA data originally recorded for global proteomic analysis to look for isomerized peptides, which occur as a result of spontaneous chemical modifications to long-lived proteins. Examination of a large set of human brain samples revealed a striking relationship between Alzheimer's disease (AD) status and isomerization of aspartic acid in a peptide from tau. Relative to controls, a surprising increase in isomer abundance was found in both autosomal dominant and sporadic AD samples. To explore potential mechanisms that might account for these observations, quantitative analysis of proteins related to isomerization repair and autophagy was performed. Differences consistent with reduced autophagic flux in AD-related samples relative to controls were found for numerous proteins, including most notably p62, a recognized indicator of autophagic inhibition. These results suggest, but do not conclusively demonstrate, that lower autophagic flux may be strongly associated with loss of function in AD brains. This study illustrates that DIA data may contain unforeseen results of interest and may be particularly useful for pilot studies investigating new research directions. In this case, a promising target for future investigations into the therapy and prevention of AD has been identified.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAutophagyBrainHumansProteomicstau ProteinsAmyloid beta-Peptidestau Proteinsage-related neurodegenerative diseaseamyloidamyloid-betaaspartic acidhippocampuslysosomeneurofibrillary tanglepost-translational modificationproteomicsproteostasis

Identifiers

PMID34818016
PMCPMC8741752
OpenAlexW3215723004

What OpenQuestion holds

Textmetadata
LicenceTDM
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.