Evidence map›Paper›PMID 34245348›Full record

ArticleArchives of toxicology2021

Inter-laboratory automation of the in vitro micronucleus assay using imaging flow cytometry and deep learning.

John W Wills, Jatin R Verma, Benjamin J Rees, Danielle S G Harte, Qiellor Haxhiraj, Claire M Barnes, Rachel Barnes, Matthew A Rodrigues, Minh Doan, Andrew Filby and 10 more

Open access · hybridAbstract readMulticenter Study
In one paragraph

Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Flow Cytometric Determination of Micronucleus Frequency.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  5. Review
  6. Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  7. Article
  8. Article
  9. The Fate of Micronuclei.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  10. Article
  11. Article
  12. Application of image-recognition techniques to automated micronucleus detection in the in vitro micronucleus assay.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024
    Article
  13. Article
  14. Development of a micronucleus test using the EpiAirway™ organotypic human airway model.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Imaging flow cytometry: a primer.Nature reviews. Methods primers · 2022
    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

20 authors at 7 institutions in 2 countries.

John W WillsCollege of Engineering, Swansea University, Swansea, UK. jw2020@cam.ac.uk.ORCID http://orcid.org/0000-0002-4347-5394
Jatin R VermaSwansea University Medical School, Swansea University, Swansea, UK.
Benjamin J ReesSwansea University Medical School, Swansea University, Swansea, UK.
Danielle S G HarteSwansea University Medical School, Swansea University, Swansea, UK.
Qiellor HaxhirajSwansea University Medical School, Swansea University, Swansea, UK.
Claire M BarnesCollege of Engineering, Swansea University, Swansea, UK.
Rachel BarnesSwansea University Medical School, Swansea University, Swansea, UK.
Matthew A RodriguesAmnis Flow Cytometry, Luminex Corporation, Seattle, WAS, USA.
Minh DoanBioimaging Analytics, GlaxoSmithKline, Collegeville, USA.
Andrew FilbyFaculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Rachel E HewittDepartment of Veterinary Medicine, Cambridge University, Cambridge, UK.
Catherine A ThorntonSwansea University Medical School, Swansea University, Swansea, UK.
James G CroninSwansea University Medical School, Swansea University, Swansea, UK.
Julia D KennyGlaxoSmithKline Research and Development Platform, Ware, UK.
Ruby BuckleyGlaxoSmithKline Research and Development Platform, Ware, UK.
Anthony M LynchSwansea University Medical School, Swansea University, Swansea, UK.
Anne E CarpenterImaging Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Huw D SummersCollege of Engineering, Swansea University, Swansea, UK.
George E Johnson *Swansea University Medical School, Swansea University, Swansea, UK. g.johnson@swan.ac.uk.
Paul Rees *College of Engineering, Swansea University, Swansea, UK. p.rees@swan.ac.uk.
Swansea University · GBGlaxoSmithKline (United Kingdom) · GBBroad Institute · USUniversity of Cambridge · GBGlaxoSmithKline (United States) · USLuminex (United States) · USNewcastle University · GB

Funding

Extracting rich information from biological imagesR35GM122547 · NIGMS · BROAD INSTITUTE, INC. · PI Anne E. Carpenter · 2017 to 2026
$6.2M
Biotechnology and Biological Sciences Research Council BB/P026818/1Engineering and Physical Sciences Research Council EP/N013506/1Life Science Research Network Wales LSBF/R3-007Medical Research Council MR/R005699/1NIGMS NIH HHS R35 GM122547NIH HHS R35 GM122547
6 · The paper itself

Abstract

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25-5.0 μg/mL) and/or carbendazim (0.8-1.6 μg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the "DeepFlow" neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for 'mononucleates', 'binucleates', 'mononucleates with MN' and 'binucleates with MN', respectively. Successful classifications of 'trinucleates' (90%) and 'tetranucleates' (88%) in addition to 'other or unscorable' phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks.

Indexed as

Deep LearningAutomation, LaboratoryBenzimidazolesCarbamatesCell LineCytokinesisDNA DamageDose-Response Relationship, DrugFlow CytometryHumansMethyl MethanesulfonateMicronucleus TestsMutagensBenzimidazolesCarbamatescarbendazimMethyl MethanesulfonateMutagensCompound screeningGenetic toxicologyHigh throughputImage analysis.Machine learningMicronucleus test

Identifiers

PMID34245348
PMCPMC8380241
OpenAlexW3181070182

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.