ArticleEnvironmental and molecular mutagenesis2015
Development of a toxicogenomics signature for genotoxicity using a dose-optimization and informatics strategy in human cells.
Article in Environmental and molecular mutagenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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.
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Who cites it
46 citing papers in PubMed.
- Analytical choices drive toxicogenomic potency estimates: a systematic evaluation of transcriptomic points of departure.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Mapping safety in space: the emerging role of spatial transcriptomics in safe drug development.Frontiers in toxicology · 2026Review
- TGx-DDI (toxicogenomic DNA damage-inducing) biomarker validation: multi-site ring trial supporting regulatory use.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics.Environmental and molecular mutagenesis · 2025Review
- Interpretation of in vitro concentration-response data for risk assessment and regulatory decision-making: Report from the 2022 IWGT quantitative analysis expert working group meeting.Environmental and molecular mutagenesis · 2025Review
- Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.Environmental and molecular mutagenesis · 2025Review
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- Deciphering per- and polyfluoroalkyl substances mode of action: comparative gene expression analysis in human liver spheroids.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Non-clinical safety assessment ofToxicological research · 2024Article
- Unlocking the Power of Transcriptomic Biomarkers in Qualitative and Quantitative Genotoxicity Assessment of Chemicals.Chemical research in toxicology · 2024Article
- Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.Toxicology letters · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Editorial:Frontiers in toxicology · 2023Article
- Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.Frontiers in toxicology · 2023Article
- Use of transcriptomics in hazard identification and next generation risk assessment: A case study with clothianidin.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application.Archives of toxicology · 2022Article
- A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Review
- Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG.International journal of molecular sciences · 2022Article
- CEBS update: curated toxicology database with enhanced tools for data integration.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The development of in vitro molecular biomarkers to accurately predict toxicological effects has become a priority to advance testing strategies for human health risk assessment. The application of in vitro transcriptomic biomarkers promises increased throughput as well as a reduction in animal use. However, the existing protocols for predictive transcriptional signatures do not establish appropriate guidelines for dose selection or account for the fact that toxic agents may have pleiotropic effects. Therefore, comparison of transcriptome profiles across agents and studies has been difficult. Here we present a dataset of transcriptional profiles for TK6 cells exposed to a battery of well-characterized genotoxic and nongenotoxic chemicals. The experimental conditions applied a new dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in preliminary dose-finding studies. The subsequent microarray-based transcriptomic analyses at the optimized dose revealed responses to the test chemicals that were typically complex, often exhibiting substantial overlap in the transcriptional responses between a variety of the agents making analysis challenging. Using the nearest shrunken centroids method we identified a panel of 65 genes that could accurately classify toxicants as genotoxic or nongenotoxic. To validate the 65-gene panel as a genomic biomarker of genotoxicity, the gene expression profiles of an additional three well-characterized model agents were analyzed and a case study demonstrating the practical application of this genomic biomarker-based approach in risk assessment was performed to demonstrate its utility in genotoxicity risk assessment.
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