ArticlePloS one2020
Mining a human transcriptome database for chemical modulators of NRF2.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 52 citations in OpenAlex.
- Chemicals in plastics differentially affect the transcriptome of MCF-7 breast cancer cells.Archives of toxicology · 2026Article
- Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) as a Biomarker for Radiation Dosimetry and Health Risk Assessment: A Review.Antioxidants (Basel, Switzerland) · 2025Review
- High-throughput transcriptomics analysis of equipotent and human relevant mixtures of BPA alternatives reveal additive effects in vitro.Archives of toxicology · 2025Article
- Impacts of Inorganic Arsenic Exposure on Genetic Stability of Human Mesenchymal Stromal Cells.Journal of applied toxicology : JAT · 2025Article
- Review
- Searching for LINCS to Stress: Using Text Mining to Automate Reference Chemical Curation.Chemical research in toxicology · 2024Article
- Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest.Scientific reports · 2024Article
- Effects of Oltipraz on the Glycolipid Metabolism and the Nrf2/HO-1 Pathway in Type 2 Diabetic Mice.Drug design, development and therapy · 2024Article
- A new approach methodology to identify tumorigenic chemicals using short-term exposures and transcript profiling.Frontiers in toxicology · 2024Article
- In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer.Cancer & metabolism · 2023Article
- Determinants of gene expression in the human liver: Impact of aging and sex on xenobiotic metabolism.Experimental gerontology · 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
- Transcriptomic Analysis of Fumarate Compounds Identifies Unique Effects of Isosorbide Di-(Methyl Fumarate) on NRF2, NF-kappaB and IRF1 Pathway Genes.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A gene expression biomarker for predictive toxicology to identify chemical modulators of NF-κB.PloS one · 2022Article
- Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue.Frontiers in genetics · 2022Article
- AKR1C1 alleviates LPS‑induced ALI in mice by activating the JAK2/STAT3 signaling pathway.Molecular medicine reports · 2021Article
- Review
- Evaluating adaptive stress response gene signatures using transcriptomics.Computational toxicology (Amsterdam, Netherlands) · 2021Article
- Role of NRF2 in Lung Cancer.Cells · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor erythroid-2 related factor 2 (NRF2) encoded by the NFE2L2 gene is a transcription factor critical for protecting cells from chemically-induced oxidative stress. We developed computational procedures to identify chemical modulators of NRF2 in a large database of human microarray data. A gene expression biomarker was built from statistically-filtered gene lists derived from microarray experiments in primary human hepatocytes and cancer cell lines exposed to NRF2-activating chemicals (oltipraz, sulforaphane, CDDO-Im) or in which the NRF2 suppressor Keap1 was knocked down by siRNA. Directionally consistent biomarker genes were further filtered for those dependent on NRF2 using a microarray dataset from cells after NFE2L2 siRNA knockdown. The resulting 143-gene biomarker was evaluated as a predictive tool using the correlation-based Running Fisher algorithm. Using 59 gene expression comparisons from chemically-treated cells with known NRF2 activating potential, the biomarker gave a balanced accuracy of 93%. The biomarker was comprised of many well-known NRF2 target genes (AKR1B10, AKR1C1, NQO1, TXNRD1, SRXN1, GCLC, GCLM), 69% of which were found to be bound directly by NRF2 using ChIP-Seq. NRF2 activity was assessed across ~9840 microarray comparisons from ~1460 studies examining the effects of ~2260 chemicals in human cell lines. A total of 260 and 43 chemicals were found to activate or suppress NRF2, respectively, most of which have not been previously reported to modulate NRF2 activity. Using a NRF2-responsive reporter gene in HepG2 cells, we confirmed the activity of a set of chemicals predicted using the biomarker. The biomarker will be useful for future gene expression screening studies of environmentally-relevant chemicals.
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.