Evidence map›Paper›PMID 39159848›Full record

ArticleToxicology and applied pharmacology2024

High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells.

Joseph L Bundy, Logan J Everett, Jesse D Rogers, Jo Nyffeler, Gabrielle Byrd, Megan Culbreth, Derik E Haggard, Laura J Word, Bryant A Chambers, Sarah Davidson-Fritz and 6 more

Abstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

16 authors.

Joseph L BundyCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America. Electronic address: bundy.joseph@epa.gov.
Logan J EverettCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Jesse D RogersCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, 37831, United States of America.
Jo NyffelerCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, 37831, United States of America.
Gabrielle ByrdCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America; Oak Ridge Associated Universities (ORAU), Oak Ridge, TN, 37831, United States of America.
Megan CulbrethCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Derik E HaggardCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Laura J WordCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Bryant A ChambersCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Sarah Davidson-FritzCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Felix HarrisCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America; Oak Ridge Associated Universities (ORAU), Oak Ridge, TN, 37831, United States of America.
Clinton WillisCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Katie Paul-FriedmanCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Imran ShahCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Richard JudsonCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.
Joshua A HarrillCenter for Computational Toxicology & Exposure, Office of Research and Development, US Environmental Protection Agency, Durham, NC 27711, United States of America.

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

New approach methodologies (NAMs) aim to accelerate the pace of chemical risk assessment while simultaneously reducing cost and dependency on animal studies. High Throughput Transcriptomics (HTTr) is an emerging NAM in the field of chemical hazard evaluation for establishing in vitro points-of-departure and providing mechanistic insight. In the current study, 1201 test chemicals were screened for bioactivity at eight concentrations using a 24-h exposure duration in the human- derived U-2 OS osteosarcoma cell line with HTTr. Assay reproducibility was assessed using three reference chemicals that were screened on every assay plate. The resulting transcriptomics data were analyzed by aggregating signal from genes into signature scores using gene set enrichment analysis, followed by concentration-response modeling of signatures scores. Signature scores were used to predict putative mechanisms of action, and to identify biological pathway altering concentrations (BPACs). BPACs were consistent across replicates for each reference chemical, with replicate BPAC standard deviations as low as 5.6 × 10

Indexed as

Gene Expression ProfilingHigh-Throughput Screening AssaysTranscriptomeCell Line, TumorDose-Response Relationship, DrugHumansOsteosarcomaReproducibility of ResultsRisk AssessmentComputational toxicologyHigh Throughput TranscriptomicsSignature scoringU-2 OS

Identifiers

PMID39159848
PMCPMC11626688

What OpenQuestion holds

Textmetadata
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.