Evidence map›Paper›PMID 37341741›Full record

ArticleArchives of toxicology2023

Duplex sequencing provides detailed characterization of mutation frequencies and spectra in the bone marrow of MutaMouse males exposed to procarbazine hydrochloride.

Annette E Dodge, Danielle P M LeBlanc, Gu Zhou, Andrew Williams, Matthew J Meier, Phu Van, Fang Yin Lo, Charles C Valentine Iii, Jesse J Salk, Carole L Yauk and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Complex versus simpleScience advances · 2026
    Article
  5. Article
  6. Detection of mutations: from Ames test to duplex sequencing.Frontiers in molecular biosciences · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Aflatoxin BEnvironmental and molecular mutagenesis · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Dose-Related Mutagenic and Clastogenic Effects of Benzo[Environmental science & technology · 2024
    Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 2 countries.

Annette E DodgeEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0002-0446-9055
Danielle P M LeBlancEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0002-3847-8371
Gu ZhouEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
Andrew WilliamsEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0002-7637-7686
Matthew J MeierEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0001-8199-8754
Phu VanTwinStrand Biosciences Inc., Seattle, Washington, USA.ORCID http://orcid.org/0000-0001-8605-316X
Fang Yin LoTwinStrand Biosciences Inc., Seattle, Washington, USA.ORCID http://orcid.org/0000-0002-8974-6508
Charles C Valentine IiiTwinStrand Biosciences Inc., Seattle, Washington, USA.ORCID http://orcid.org/0000-0001-5630-7368
Jesse J SalkTwinStrand Biosciences Inc., Seattle, Washington, USA.ORCID http://orcid.org/0000-0002-7804-0550
Carole L YaukDepartment of Biology, University of Ottawa, Ottawa, Ontario, Canada. carole.yauk@uottawa.ca.ORCID http://orcid.org/0000-0002-6725-3454
Francesco MarchettiEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada. francesco.marchetti@hc-sc.gc.ca.ORCID http://orcid.org/0000-0002-9435-4867
Health Canada · CABlaze Bioscience (United States) · USUniversity of Ottawa · CA

Funding

Development of a Genotoxicity Assay using Duplex SequencingR44ES030642 · NIEHS · TWINSTRAND BIOSCIENCES, INC. · PI SALK, JESSE J · 2019 to 2021
$1.7M
NIEHS NIH HHS R44 ES030642
6 · The paper itself

Abstract

Mutagenicity testing is an essential component of health safety assessment. Duplex Sequencing (DS), an emerging high-accuracy DNA sequencing technology, may provide substantial advantages over conventional mutagenicity assays. DS could be used to eliminate reliance on standalone reporter assays and provide mechanistic information alongside mutation frequency (MF) data. However, the performance of DS must be thoroughly assessed before it can be routinely implemented for standard testing. We used DS to study spontaneous and procarbazine (PRC)-induced mutations in the bone marrow (BM) of MutaMouse males across a panel of 20 diverse genomic targets. Mice were exposed to 0, 6.25, 12.5, or 25 mg/kg-bw/day for 28 days by oral gavage and BM sampled 42 days post-exposure. Results were compared with those obtained using the conventional lacZ viral plaque assay on the same samples. DS detected significant increases in mutation frequencies and changes to mutation spectra at all PRC doses. Low intra-group variability within DS samples allowed for detection of increases at lower doses than the lacZ assay. While the lacZ assay initially yielded a higher fold-change in mutant frequency than DS, inclusion of clonal mutations in DS mutation frequencies reduced this discrepancy. Power analyses suggested that three animals per dose group and 500 million duplex base pairs per sample is sufficient to detect a 1.5-fold increase in mutations with > 80% power. Overall, we demonstrate several advantages of DS over classical mutagenicity assays and provide data to support efforts to identify optimal study designs for the application of DS as a regulatory test.

Indexed as

Bone MarrowMutation RateAnimalsLac OperonMaleMiceMice, TransgenicMutagenicity TestsMutagensMutationProcarbazineMutagensProcarbazineDuplex sequencingecNGSError-corrected sequencingGenetic toxicologyMutagenesisTransgenic rodent assay

Identifiers

PMID37341741
PMCPMC10322784
OpenAlexW4381470516

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.