Evidence map›Paper›PMID 40874998›Full record

ArticleArchives of toxicology2025

Smaller scale, same impact: replicating high-throughput phenotypic profiling in a medium-throughput lab for use in chemical risk assessment.

Eunnara Cho, Stephen D Baird, Kristin M Eccles

Abstract read
In one paragraph

Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Eunnara ChoEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch (HECSB) Health Canada, Ottawa, ON, K1A 0K9, Canada.ORCID 0000-0001-9942-0053
Stephen D BairdHigh-Throughput Screening Lab, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, K1H 8L1, Canada.
Kristin M EcclesEnvironmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch (HECSB) Health Canada, Ottawa, ON, K1A 0K9, Canada. kristin.eccles@hc-sc.gc.ca.

Funding

Health Canada Chemical Management Plan
6 · The paper itself

Abstract

Cell Painting visualizes toxicity-induced morphological changes by staining cellular structures with fluorescent dyes. Coupled with high-content imaging and analysis software, Cell Painting allows high-throughput phenotypic profiling (HTPP) to quantify phenotypic changes and estimate points of departure for toxicity assessments. Regulatory agencies have applied HTPP in 384-well plates for chemical hazard screening. In this study, established protocols for 384-well plates were adapted for use in 96-well plates to increase accessibility for laboratories with lower throughput. U-2 OS human osteosarcoma cells in 96-well plates were exposed to 12 phenotypic reference compounds for 24 h before fixation and staining with fluorescent dyes (golgi apparatus, endoplasmic reticulum, nucleic acids, cytoskeleton, mitochondria). Four independent chemical exposures across eight concentrations generated four biological replicates. Stained cells were imaged on an Opera Phenix, a high-content imaging system, and the Columbus analysis software extracted numerical values for 1300 morphological features. Features were normalized to control cells, followed by principal component analysis and a calculation of Mahalanobis for each treatment concentration. Mahalanobis distances were modeled to calculate benchmark concentrations (BMC) for chemicals. Most BMCs differed by less than one order of magnitude across experiments, demonstrating intra-laboratory consistency. Compared to published BMCs, ten compounds had comparable BMCs in both plate formats. In addition, we observed a significant inverse relationship between seeding density and Mahalanobis distances, suggesting that experimental factors like cell density may influence BMCs. Overall, we demonstrate that Cell Painting is adaptable across formats and laboratories, supporting efforts to develop and validate it as a complementary new approach methodology to existing toxicity tests.

Indexed as

High-Throughput Screening AssaysToxicity TestsCell Line, TumorFluorescent DyesHumansPhenotypeRisk AssessmentSoftwareFluorescent DyesCell PaintingHigh-content imagingHigh-throughput phenotypic profilingToxicity assessment

Identifiers

PMID40874998
PMCPMC12477089

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LicenceCC BY
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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.