ArticleToxicology and applied pharmacology2020
Bioactivity screening of environmental chemicals using imaging-based high-throughput phenotypic profiling.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
- A human PBMC-based new approach method reveals PFAS-driven T-cell proliferation and immune dysregulation.Archives of toxicology · 2026Article
- A High-Content Imaging Pipeline to Investigate Subcytotoxic Effects in RTgill-W1 Cells.Environmental science & technology · 2026Article
- Building trust in the integration of artificial intelligence into chemical risk assessment: findings from the 2024 ECETOC workshop.Archives of toxicology · 2026Article
- Cell Painting PLUS: An Iterative Staining-Elution Protocol for High-Content Phenotypic Screenings.Current protocols · 2026Article
- Temperature-Gradient Transcriptomic Atlas Reveals the PPAR Signaling Pathway Dysfunction in Heat Stroke Induced Liver Injury.FASEB bioAdvances · 2026Article
- Comprehensive profiling of metal compound toxicity: potential novel targets and mechanistic insights using Tox21 screening.Journal of hazardous materials advances · 2026Article
- Article
- Analyzing Cell Painting PLUS Data Using Cell Profiler and KNIME Analytics Platform.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The OASIS Consortium: integrating multi-omics technologies to transform chemical safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Assessing the impact of in vitro xenobiotic metabolism on estrogenic chemical bioactivity in high-throughput profiling assays.Toxicology · 2025Article
- Smaller scale, same impact: replicating high-throughput phenotypic profiling in a medium-throughput lab for use in chemical risk assessment.Archives of toxicology · 2025Article
- Alternate dyes for image-based profiling assays.SLAS discovery : advancing life sciences R & D · 2025Article
- Testing Strategies for Metabolite-Mediated Neurotoxicity.International journal of molecular sciences · 2025Review
- Phenotypic Profiling of 6PPD, 6PPD-quinone and Structurally Diverse Antiozonants in RTgill-W1 Cells Using the Cell Painting Assay.Environmental science & technology letters · 2025Article
- Cell Painting PLUS: expanding the multiplexing capacity of Cell Painting-based phenotypic profiling using iterative staining-elution cycles.Nature communications · 2025Article
- High-content microscopy and machine learning characterize a cell morphology signature ofbioRxiv : the preprint server for biology · 2025Article
- Bridging imaging-based in vitro methods from biomedical research to regulatory toxicology.Archives of toxicology · 2025Review
- Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Exploring NLRP3-related phenotypic fingerprints in human macrophages using Cell Painting assay.iScience · 2025Article
- Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation.iScience · 2025Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
The present study adapted an existing high content imaging-based high-throughput phenotypic profiling (HTPP) assay known as "Cell Painting" for bioactivity screening of environmental chemicals. This assay uses a combination of fluorescent probes to label a variety of organelles and measures a large number of phenotypic features at the single cell level in order to detect chemical-induced changes in cell morphology. First, a small set of candidate phenotypic reference chemicals (n = 14) known to produce changes in the cellular morphology of U-2 OS cells were identified and screened at multiple time points in concentration-response format. Many of these chemicals produced distinct cellular phenotypes that were qualitatively similar to those previously described in the literature. A novel workflow for phenotypic feature extraction, concentration-response modeling and determination of in vitro thresholds for chemical bioactivity was developed. Subsequently, a set of 462 chemicals from the ToxCast library were screened in concentration-response mode. Bioactivity thresholds were calculated and converted to administered equivalent doses (AEDs) using reverse dosimetry. AEDs were then compared to effect values from mammalian toxicity studies. In many instances (68%), the HTPP-derived AEDs were either more conservative than or comparable to the in vivo effect values. Overall, we conclude that the HTPP assay can be used as an efficient, cost-effective and reproducible screening method for characterizing the biological activity and potency of environmental chemicals for potential use in in vitro-based safety assessments.
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