Evidence map›Paper›PMID 25012808›Full record

ArticleScientific reports2014

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway.

Ruili Huang, Srilatha Sakamuru, Matt T Martin, David M Reif, Richard S Judson, Keith A Houck, Warren Casey, Jui-Hua Hsieh, Keith R Shockley, Patricia Ceger and 12 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 168 citations in OpenAlex.

  1. Article
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  6. Lessons learned from evaluating defined chemical mixtures in a high-throughput estrogen receptor assay system.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  7. Article
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  11. Article
  12. Article
  13. Bayesian matrix completion for hypothesis testing.Journal of the Royal Statistical Society. Series C, Applied statistics · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Machine Learning and Artificial Intelligence in Toxicological Sciences.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Review
  19. Review
  20. Article

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 1 country.

Ruili HuangNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Srilatha SakamuruNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Matt T MartinNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
David M ReifNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Richard S JudsonNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Keith A HouckNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Warren CaseyDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Jui-Hua HsiehDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Keith R ShockleyDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Patricia CegerILS Inc., Research Triangle Park, NC 27709, USA.
Jennifer FostelDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Kristine L WittDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Weida TongDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Daniel M RotroffNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Tongan ZhaoNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Paul ShinnNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Anton SimeonovNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
David J DixNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Christopher P AustinNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Robert J KavlockNational Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Raymond R TiceDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Menghang XiaNIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
National Institute of Environmental Health Sciences · USNational Institutes of Health · USResearch Triangle Park Foundation · USEnvironmental Protection Agency · USNational Center for Advancing Translational Sciences · USUnited States Food and Drug Administration · US

Funding

NIH Chemical Genomics CenterZIBTR000004 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI MCKEW, JOHN · 2012 to 2014
$52.3M
TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
Analysis of Quantitative High Throughput Screening DataZIAES102865 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI SHOCKLEY, KEITH · 2010 to 2025
$2.8M
Analysis activities for the National Toxicology Program (NTP)ZIAES103226 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BUCHER, JOHN · 2014 to 2014
$622k
NIEHS NIH HHS Y02 ES007020NIEHS NIH HHS #Y2-ES-7020-01
6 · The paper itself

Abstract

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα β-lactamase cell line), in a quantitative high-throughput screening (qHTS) format. The ability of the two assays to correctly identify ERα agonists and antagonists was evaluated using a set of 39 reference compounds with known ERα activity. Although both assays demonstrated adequate (i.e. >80%) predictivity, the ER-luc assay was more sensitive and the ER-bla assay more specific. The qHTS assay results were compared with results from previously published ERα binding assay data and showed >80% consistency. Actives identified from both the ER-bla and ER-luc assays were analyzed for structure-activity relationships (SARs) revealing known and potentially novel ERα active structure classes. The results demonstrate the feasibility of qHTS to identify environmental chemicals with the potential to interact with the ERα signaling pathway and the two different assay formats improve the confidence in correctly identifying these chemicals.

Indexed as

Cell LineEstrogen Receptor alphaGenes, ReporterHEK293 CellsHigh-Throughput Screening AssaysHumansLigandsProtein BindingSignal TransductionSmall Molecule LibrariesStructure-Activity RelationshipEstrogen Receptor alphaLigandsSmall Molecule Libraries

Identifiers

PMID25012808
PMCPMC4092345
OpenAlexW1967434540

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.