Evidence map›Paper›PMID 25904095›Full record

ArticleJournal of biomolecular screening2015

A Data Analysis Pipeline Accounting for Artifacts in Tox21 Quantitative High-Throughput Screening Assays.

Jui-Hua Hsieh, Alexander Sedykh, Ruili Huang, Menghang Xia, Raymond R Tice

Abstract read
In one paragraph

Article in Journal of biomolecular screening, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
–field-weighted citation impact
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

39 citing papers in PubMed.

  1. Article
  2. Article
  3. Bayesian matrix completion for hypothesis testing.Journal of the Royal Statistical Society. Series C, Applied statistics · 2023
    Article
  4. Article
  5. ALOHA: Aggregated local extrema splines for high-throughput dose-response analysis.Computational toxicology (Amsterdam, Netherlands) · 2022
    Article
  6. Accounting for Artifacts in High-Throughput Toxicity Assays.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  7. Article
  8. Review
  9. Article
  10. Selecting a minimal set of androgen receptor assays for screening chemicals.Regulatory toxicology and pharmacology : RTP · 2020
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Screening for Developmental Neurotoxicity at the National Toxicology Program: The Future Is Here.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    Article
  20. Article
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

5 authors.

Jui-Hua HsiehDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA jui-hua.hsieh@nih.gov.
Alexander SedykhMultiCASE Inc., Beachwood, OH, USA.
Ruili HuangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Menghang XiaNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Raymond R TiceDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Funding

Biomolecular Screening and Alternative Approaches for the National Toxicology ProgramZIAES103318 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CASEY, WARREN · 2016 to 2021
$25.0M
TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
Toxicology in the 21st Century Program (Tox21) - Systems ToxicologyZIATR000038 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI XIA, MENGHANG · 2015 to 2025
$5.7M
Toxicology in the 21st Century Program (Tox21) Computational ToxicologyZICTR000040 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI HUANG, RUILI · 2015 to 2015
$50k
Intramural NIH HHS Z99 TR999999NIEHS NIH HHS Y02 ES007020NIEHS NIH HHS Y2-ES-7020-01
6 · The paper itself

Abstract

A main goal of the U.S. Tox21 program is to profile a 10K-compound library for activity against a panel of stress-related and nuclear receptor signaling pathway assays using a quantitative high-throughput screening (qHTS) approach. However, assay artifacts, including nonreproducible signals and assay interference (e.g., autofluorescence), complicate compound activity interpretation. To address these issues, we have developed a data analysis pipeline that includes an updated signal noise-filtering/curation protocol and an assay interference flagging system. To better characterize various types of signals, we adopted a weighted version of the area under the curve (wAUC) to quantify the amount of activity across the tested concentration range in combination with the assay-dependent point-of-departure (POD) concentration. Based on the 32 Tox21 qHTS assays analyzed, we demonstrate that signal profiling using wAUC affords the best reproducibility (Pearson's r = 0.91) in comparison with the POD (0.82) only or the AC(50) (i.e., half-maximal activity concentration, 0.81). Among the activity artifacts characterized, cytotoxicity is the major confounding factor; on average, about 8% of Tox21 compounds are affected, whereas autofluorescence affects less than 0.5%. To facilitate data evaluation, we implemented two graphical user interface applications, allowing users to rapidly evaluate the in vitro activity of Tox21 compounds.

Indexed as

ArtifactsData Interpretation, StatisticalDrug DiscoveryHigh-Throughput Screening AssaysHumansReproducibility of ResultsSignal-To-Noise RatioSmall Molecule LibrariesUnited StatesSmall Molecule Librariesconcentration-response curvein vitro activity profilingqHTS data analysisTox21

Identifiers

PMID25904095
PMCPMC4568956

What OpenQuestion holds

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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.