ArticleArchives of toxicology2016
High-throughput imaging-based nephrotoxicity prediction for xenobiotics with diverse chemical structures.
Article in Archives of toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 63 citations in OpenAlex.
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- Application of Cell Painting for chemical hazard evaluation in support of screening-level chemical assessments.Toxicology and applied pharmacology · 2023Article
- Reference compounds for characterizing cellular injury in high-content cellular morphology assays.Nature communications · 2023Article
- Integration of High-Throughput Imaging and Multiparametric Metabolic Profiling Reveals a Mitochondrial Mechanism of Tenofovir Toxicity.Function (Oxford, England) · 2023Article
- High-throughput "read-on-ski" automated imaging and label-free detection system for toxicity screening of compounds using personalised human kidney organoids.Journal of Zhejiang University. Science. B · 2022Article
- Drug toxicity in the proximal tubule: new models, methods and mechanisms.Pediatric nephrology (Berlin, Germany) · 2022Review
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- Group VIII Metal Carbonyl Cluster-Boronic Acid Conjugates: Cytotoxicity and Mode of Action Studies.ACS omega · 2021Article
- Image-based profiling for drug discovery: due for a machine-learning upgrade?Nature reviews. Drug discovery · 2021Review
- Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids.Archives of toxicology · 2021Article
- Article
- Genetically Engineered Human Kidney Cells for Real-Time Cytotoxicity Testing In Vitro.Molecular biotechnology · 2020Article
- In vitro prediction of organ toxicity: the challenges of scaling and secondary mechanisms of toxicity.Archives of toxicology · 2020Article
- Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Review of high-content screening applications in toxicology.Archives of toxicology · 2019Review
- A Systems Toxicology Approach for the Prediction of Kidney Toxicity and Its Mechanisms In Vitro.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kidney is a major target for xenobiotics, which include drugs, industrial chemicals, environmental toxicants and other compounds. Accurate methods for screening large numbers of potentially nephrotoxic xenobiotics with diverse chemical structures are currently not available. Here, we describe an approach for nephrotoxicity prediction that combines high-throughput imaging of cultured human renal proximal tubular cells (PTCs), quantitative phenotypic profiling, and machine learning methods. We automatically quantified 129 image-based phenotypic features, and identified chromatin and cytoskeletal features that can predict the human in vivo PTC toxicity of 44 reference compounds with ~82 % (primary PTCs) or 89 % (immortalized PTCs) test balanced accuracies. Surprisingly, our results also revealed that a DNA damage response is commonly induced by different PTC toxicants that have diverse chemical structures and injury mechanisms. Together, our results show that human nephrotoxicity can be predicted with high efficiency and accuracy by combining cell-based and computational methods that are suitable for automation.
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Registered trials
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.