ArticleEnvironmental and molecular mutagenesis2019
Assessment of the performance of the TGx-DDI biomarker to detect DNA damage-inducing agents using quantitative RT-PCR in TK6 cells.
Article in Environmental and molecular mutagenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 41 citations in OpenAlex.
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- Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics.Environmental and molecular mutagenesis · 2025Review
- Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines.Environmental and molecular mutagenesis · 2025Review
- 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
- 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
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- Signature analysis of high-throughput transcriptomics screening data for mechanistic inference and chemical grouping.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells.Toxicology and applied pharmacology · 2024Article
- Searching for LINCS to Stress: Using Text Mining to Automate Reference Chemical Curation.Chemical research in toxicology · 2024Article
- Unlocking the Power of Transcriptomic Biomarkers in Qualitative and Quantitative Genotoxicity Assessment of Chemicals.Chemical research in toxicology · 2024Article
- A new approach methodology to identify tumorigenic chemicals using short-term exposures and transcript profiling.Frontiers in toxicology · 2024Article
- Exploring the effects of experimental parameters and data modeling approaches on in vitro transcriptomic point-of-departure estimates.Toxicology · 2024Article
- Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.Frontiers in toxicology · 2023Article
- CEBS update: curated toxicology database with enhanced tools for data integration.Nucleic acids research · 2022Article
- Integrated Genotoxicity Testing of three anti-infective drugs using the TGx-DDI transcriptomic biomarker and high-throughput CometChipFrontiers in toxicology · 2022Article
- GADD45 in Stress Signaling, Cell Cycle Control, and Apoptosis.Advances in experimental medicine and biology · 2022Article
- A gene expression biomarker for predictive toxicology to identify chemical modulators of NF-κB.PloS one · 2022Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells.Archives of toxicology · 2021Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene expression biomarkers are now available for application in the identification of genotoxic hazards. The TGx-DDI transcriptomic biomarker can accurately distinguish DNA damage-inducing (DDI) from non-DDI exposures based on changes in the expression of 64 biomarker genes. The 64 genes were previously derived from whole transcriptome DNA microarray profiles of 28 reference agents (14 DDI and 14 non-DDI) after 4 h treatments of TK6 human lymphoblastoid cells. To broaden the applicability of TGx-DDI, we tested the biomarker using quantitative RT-PCR (qPCR), which is accessible to most molecular biology laboratories. First, we selectively profiled the expression of the 64 biomarker genes using TaqMan qPCR assays in 96-well arrays after exposing TK6 cells to the 28 reference agents for 4 h. To evaluate the classification capability of the qPCR profiles, we used the reference qPCR signature to classify 24 external validation chemicals using two different methods-a combination of three statistical analyses and an alternative, the Running Fisher test. The qPCR results for the reference set were comparable to the original microarray biomarker; 27 of the 28 reference agents (96%) were accurately classified. Moreover, the two classification approaches supported the conservation of TGx-DDI classification capability using qPCR; the combination of the two approaches accurately classified 21 of the 24 external validation chemicals, demonstrating 100% sensitivity, 81% specificity, and 91% balanced accuracy. This study demonstrates that qPCR can be used when applying the TGx-DDI biomarker and will improve the accessibility of TGx-DDI for genotoxicity screening. Environ. Mol. Mutagen. 60: 122-133, 2019. © 2018 Her Majesty the Queen in Right of Canada Environmental and Molecular Mutagenesis.
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