ArticleScientific reports2021
Transforming early pharmaceutical assessment of genotoxicity: applying statistical learning to a high throughput, multi end point in vitro micronucleus assay.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
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- From Forestry By-Product to Functional Food Ingredient Innovation: Antiproliferative, Antimetastatic and Antiplasmodial Activities of Norway Spruce Sawdust Extract.Foods (Basel, Switzerland) · 2026Article
- Critical Evaluation of Methods for the Identification of Aneugens.Environmental and molecular mutagenesis · 2025Review
- Silver(I) Ions Bridging Oxadiazole-2-thione Derivatives with Mitochondriotropic Agents: A Promising Strategy for Potent Anticancer Chemotherapy.Inorganic chemistry · 2025Article
- A comprehensive update on the application of high-throughput fluorescence imaging for novel drug discovery.Expert opinion on drug discovery · 2025Review
- A multi-biomarker micronucleus assay using imaging flow cytometry.Archives of toxicology · 2024Article
- IL-6 knockdown in a model of the human bone marrow, abrogates DNA damage induction in bystander cells post-chemotherapy induced cytokine release syndrome.Translational oncology · 2024Article
- Visualization strategies to aid interpretation of high-dimensional genotoxicity data.Environmental and molecular mutagenesis · 2024Article
- An integrated in vitro carcinogenicity test that distinguishes between genotoxic carcinogens, non-genotoxic carcinogens, and non-carcinogens.Mutagenesis · 2024Review
- Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow.Mutagenesis · 2023Article
- Evaluation of Antioxidant Activity, Cytotoxicity, and Genotoxicity ofLife (Basel, Switzerland) · 2023Article
- Automatic recognition of micronucleus by combining attention mechanism and AlexNet.BMC medical informatics and decision making · 2022Article
- A novel in vitro 3D model of the human bone marrow to bridge the gap between in vitro and in vivo genotoxicity testing.Mutagenesis · 2022Article
- In vitro human cell-based aneugen molecular mechanism assay.Environmental and molecular mutagenesis · 2022Article
- Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation.European journal of medicinal chemistry · 2021Article
- Article
- A MATLAB-based program for three-dimensional quantitative analysis of micronuclei reveals that neuroinflammation induces micronuclei formation in the brain.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To provide a comprehensive analysis of small molecule genotoxic potential we have developed and validated an automated, high-content, high throughput, image-based in vitro Micronucleus (IVM) assay. This assay simultaneously assesses micronuclei and multiple additional cellular markers associated with genotoxicity. Acoustic dosing (≤ 2 mg) of compound is followed by a 24-h treatment and a 24-h recovery period. Confocal images are captured [Cell Voyager CV7000 (Yokogawa, Japan)] and analysed using Columbus software (PerkinElmer). As standard the assay detects micronuclei (MN), cytotoxicity and cell-cycle profiles from Hoechst phenotypes. Mode of action information is primarily determined by kinetochore labelling in MN (aneugencity) and γH2AX foci analysis (a marker of DNA damage). Applying computational approaches and implementing machine learning models alongside Bayesian classifiers allows the identification of, with 95% accuracy, the aneugenic, clastogenic and negative compounds within the data set (Matthews correlation coefficient: 0.9), reducing analysis time by 80% whilst concurrently minimising human bias. Combining high throughput screening, multiparametric image analysis and machine learning approaches has provided the opportunity to revolutionise early Genetic Toxicology assessment within AstraZeneca. By multiplexing assay endpoints and minimising data generation and analysis time this assay enables complex genotoxicity safety assessments to be made sooner aiding the development of safer drug candidates.
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