ArticlePloS one2015
Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD) and Multiple Approaches for Selection of Chemical Point of Departure (PoD).
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 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
- Comprehensive analysis of high-throughput transcriptomics to distinguish drug-induced liver injury (DILI) phenotypes.Archives of toxicology · 2025Review
- Bioinformatic workflows for deriving transcriptomic points of departure: current status, data gaps, and research priorities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Investigating the dependency of in vitro benchmark concentrations on exposure time in transcriptomics experiments.Toxicology in vitro : an international journal published in association with BIBRA · 2024Article
- Applying genomics in regulatory toxicology: a report of the ECETOC workshop on omics threshold on non-adversity.Archives of toxicology · 2023Article
- Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.Toxicology letters · 2023Article
- From vision toward best practices: EvaluatingFrontiers in toxicology · 2023Article
- Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay.Current research in toxicology · 2023Article
- Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs.Nucleic acids research · 2022Article
- Latent Variables Capture Pathway-Level Points of Departure in High-Throughput Toxicogenomic Data.Chemical research in toxicology · 2022Article
- ALOHA: Aggregated local extrema splines for high-throughput dose-response analysis.Computational toxicology (Amsterdam, Netherlands) · 2022Article
- Linking Coregulated Gene Modules with Polycyclic Aromatic Hydrocarbon-Related Cancer Risk in the 3D Human Bronchial Epithelium.Chemical research in toxicology · 2021Article
- Construction of Mode of Action for Cadmium-Induced Renal Tubular Dysfunction Based on a Toxicity Pathway-Oriented Approach.Frontiers in genetics · 2021Article
- A set of six Gene expression biomarkers and their thresholds identify rat liver tumorigens in short-term assays.Toxicology · 2020Article
- Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory Aspects.Nanomaterials (Basel, Switzerland) · 2020Review
- A toxicogenomic approach for the risk assessment of the food contaminant acetamide.Toxicology and applied pharmacology · 2020Article
- The use of evidence from high-throughput screening and transcriptomic data in human health risk assessments.Toxicology and applied pharmacology · 2019Article
- Considerations for Strategic Use of High-Throughput Transcriptomics Chemical Screening Data in Regulatory Decisions.Current opinion in toxicology · 2019Article
- The application of transcriptional benchmark dose modeling for deriving thresholds of effects associated with solar-simulated ultraviolet radiation exposure.Environmental and molecular mutagenesis · 2018Article
- Recommended approaches in the application of toxicogenomics to derive points of departure for chemical risk assessment.Archives of toxicology · 2017Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many regulatory agencies are exploring ways to integrate toxicogenomic data into their chemical risk assessments. The major challenge lies in determining how to distill the complex data produced by high-content, multi-dose gene expression studies into quantitative information. It has been proposed that benchmark dose (BMD) values derived from toxicogenomics data be used as point of departure (PoD) values in chemical risk assessments. However, there is limited information regarding which genomics platforms are most suitable and how to select appropriate PoD values. In this study, we compared BMD values modeled from RNA sequencing-, microarray-, and qPCR-derived gene expression data from a single study, and explored multiple approaches for selecting a single PoD from these data. The strategies evaluated include several that do not require prior mechanistic knowledge of the compound for selection of the PoD, thus providing approaches for assessing data-poor chemicals. We used RNA extracted from the livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd) and carcinogenic (4, 8 mkd) doses of furan for 21 days. We show that transcriptional BMD values were consistent across technologies and highly predictive of the two-year cancer bioassay-based PoD. We also demonstrate that filtering data based on statistically significant changes in gene expression prior to BMD modeling creates more conservative BMD values. Taken together, this case study on mice exposed to furan demonstrates that high-content toxicogenomics studies produce robust data for BMD modelling that are minimally affected by inter-technology variability and highly predictive of cancer-based PoD doses.
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