Evidence map›Paper›PMID 37843128›Full record

ArticleNucleic acids research2023

Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans.

Axel Guilbaud, Farzan Ghanegolmohammadi, Yijun Wang, Jiapeng Leng, Alexander Kreymerman, Jacqueline Gamboa Varela, Jessica Garbern, Hannah Elwell, Fang Cao, Elisabeth M Ricci-Blair and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
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  3. 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

21 authors at 6 institutions in 2 countries.

Axel GuilbaudDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Farzan GhanegolmohammadiDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Yijun WangDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jiapeng LengDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Alexander KreymermanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jacqueline Gamboa VarelaDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jessica GarbernDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Hannah ElwellDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Fang CaoDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Elisabeth M Ricci-BlairDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Cui LiangSingapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore.
Seetharamsing BalamkunduSingapore-MIT Alliance for Research and Technology, Antimicrobial Resistance Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore 138602, Singapore.
Charles VidoudezHarvard Center for Mass Spectrometry, Harvard University, Cambridge, MA 02138, USA.
Michael S DeMottDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Kenneth BediUniversity of Pennsylvania Cardiovascular Institute, Philadelphia, PA, USA.
Kenneth B MarguliesUniversity of Pennsylvania Cardiovascular Institute, Philadelphia, PA, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0003-3689-554X
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Amanda Barkley-LevensonDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Richard T LeeDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Peter C DedonDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.ORCID 0000-0003-0011-3067
Harvard University · USSingapore-MIT Alliance for Research and Technology · SGCardiovascular Institute of the South · USMassachusetts Institute of Technology · USUniversity of California San Diego · USRush University Medical Center · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YAFFE, MICHAEL B · 1985 to 2020
$25.6M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Novel Age-Dependent DNA ModificationsR01AG063341 · NIA · HARVARD UNIVERSITY · PI DEDON, PETER C, LEE, RICHARD T · 2018 to 2022
$2.0M
A Novel Pharmacotherapy for Alcoholism: Evaluation of Reward, Aversion, Compulsivity, Withdrawal & ReinstatementR01AA026281 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALMER, ABRAHAM A · 2018 to 2022
$2.0M
NIAAA NIH HHS R01 AA026281NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG063341NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIEHS NIH HHS P30 ES002109
6 · The paper itself

Abstract

DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC-MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1-26-month-old rats and 111 in human heart and brain by 'stepped MRM' LC-MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.

Indexed as

DNADNA AdductsAnimalsChromatography, LiquidFemaleHumansMaleRatsRodentiaTandem Mass SpectrometryDNADNA Adducts

Identifiers

PMID37843128
PMCPMC10639045
OpenAlexW4387661215

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.