ArticleToxicological sciences : an official journal of the Society of Toxicology2024
Signature analysis of high-throughput transcriptomics screening data for mechanistic inference and chemical grouping.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed.
- Cross-study analysis identifies estrogen depletion and exposure duration as key determinants of bisphenol A transcriptomic potency in MCF-7 cells.Toxicology reports · 2026Article
- 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
- Chemicals in plastics differentially affect the transcriptome of MCF-7 breast cancer cells.Archives of toxicology · 2026Article
- Integrating chemical structure and high-throughput transcriptomics for mechanistically interpretable Tox21 bioactivity prediction.Journal of cheminformatics · 2026Article
- Does consumption of a high-fructose diet during pregnancy and lactation exacerbate the effects of maternal exposure to cadmium on development and metabolic function of mouse offspring?Journal of toxicology and environmental health. Part A · 2026Article
- Zebrafish cell lines and high-throughput transcriptomics: advancing in vitro and bioinformatics methods for supporting environmental risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Comparison of whole transcriptome and targeted RNA sequencing for ecological high-throughput transcriptomics.Regulatory toxicology and pharmacology : RTP · 2025Article
- Assessing the impact of in vitro xenobiotic metabolism on estrogenic chemical bioactivity in high-throughput profiling assays.Toxicology · 2025Article
- Transferability and Reproducibility of the HepaRG CometChip Assay.Environmental and molecular mutagenesis · 2025Article
- Identifying Gene Predictors of Chemicals Linked With Breast Cancer: A Machine Learning Analysis of MCF7 Cellular Transcriptomic Screening Data.Environmental and molecular mutagenesis · 2025Article
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- macpie: Scalable workflow for high-throughput transcriptomic profiling.Computational and structural biotechnology journal · 2025Article
- An advancement in developmental and reproductive toxicity (DART) risk assessment: evaluation of a bioactivity and exposure-based NAM toolbox.Frontiers in toxicology · 2025Article
- TempO-seq and RNA-seq gene expression levels are highly correlated for most genes: A comparison using 39 human cell lines.PloS one · 2025Article
- High-throughput gene expression analysis with TempO-LINC sensitively resolves complex brain, lung and kidney heterogeneity at single-cell resolution.Scientific reports · 2024Article
- High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells.Toxicology and applied pharmacology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
High-throughput transcriptomics (HTTr) uses gene expression profiling to characterize the biological activity of chemicals in in vitro cell-based test systems. As an extension of a previous study testing 44 chemicals, HTTr was used to screen an additional 1,751 unique chemicals from the EPA's ToxCast collection in MCF7 cells using 8 concentrations and an exposure duration of 6 h. We hypothesized that concentration-response modeling of signature scores could be used to identify putative molecular targets and cluster chemicals with similar bioactivity. Clustering and enrichment analyses were conducted based on signature catalog annotations and ToxPrint chemotypes to facilitate molecular target prediction and grouping of chemicals with similar bioactivity profiles. Enrichment analysis based on signature catalog annotation identified known mechanisms of action (MeOAs) associated with well-studied chemicals and generated putative MeOAs for other active chemicals. Chemicals with predicted MeOAs included those targeting estrogen receptor (ER), glucocorticoid receptor (GR), retinoic acid receptor (RAR), the NRF2/KEAP/ARE pathway, AP-1 activation, and others. Using reference chemicals for ER modulation, the study demonstrated that HTTr in MCF7 cells was able to stratify chemicals in terms of agonist potency, distinguish ER agonists from antagonists, and cluster chemicals with similar activities as predicted by the ToxCast ER Pathway model. Uniform manifold approximation and projection (UMAP) embedding of signature-level results identified novel ER modulators with no ToxCast ER Pathway model predictions. Finally, UMAP combined with ToxPrint chemotype enrichment was used to explore the biological activity of structurally related chemicals. The study demonstrates that HTTr can be used to inform chemical risk assessment by determining in vitro points of departure, predicting chemicals' MeOA and grouping chemicals with similar bioactivity profiles.
Indexed as
Identifiers
What OpenQuestion holds
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.