Evidence map›Paper›PMID 30263952›Full record

ArticleScience advances2018

Evaluating biological activity of compounds by transcription factor activity profiling.

Alexander Medvedev, Matt Moeser, Liubov Medvedeva, Elena Martsen, Alexander Granick, Lydia Raines, Ming Zeng, Sergei Makarov, Keith A Houck, Sergei S Makarov

Abstract read
In one paragraph

Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025
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  4. Burnt Plastic (Pyroplastic) from the M/VEnvironment & health (Washington, D.C.) · 2025
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  6. Review
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  9. Review
  10. Evaluation of Per- and Polyfluoroalkyl Substances (PFAS)Chemical research in toxicology · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Estimating Hepatotoxic Doses Using High-Content Imaging in Primary Hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  17. Evaluation of a multiplexed, multispecies nuclear receptor assay for chemical hazard assessment.Toxicology in vitro : an international journal published in association with BIBRA · 2021
    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

10 authors.

Alexander MedvedevAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.ORCID 0000-0001-6983-1687
Matt MoeserAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.ORCID 0000-0002-1368-5171
Liubov MedvedevaAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.
Elena MartsenAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.
Alexander GranickAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.ORCID 0000-0002-9725-102X
Lydia RainesAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.
Ming ZengAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.
Sergei MakarovAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.ORCID 0000-0001-9240-0770
Keith A HouckU.S. Environmental Protection Agency, 109 T.W. Alexander Drive, D343-03, Research Triangle Park, NC 27711, USA.ORCID 0000-0002-0055-2249
Sergei S MakarovAttagene Inc., P.O. Box 12054, Research Triangle Park, NC 27709, USA.ORCID 0000-0003-1314-6909

Funding

Predicting DILI liability by transcription factor profilingR44GM125469 · NIGMS · ATTAGENE, INC. · PI MAKAROV, SERGEI S · 2017 to 2019
$3.0M
NIGMS NIH HHS R44 GM125469
6 · The paper itself

Abstract

Assessing the biological activity of compounds is an essential objective of biomedical research. We show that one can infer the bioactivity of compounds by assessing the activity of transcription factors (TFs) that regulate gene expression. Using a multiplex reporter system, the FACTORIAL, we characterized cell response to a compound by a quantitative signature, the TF activity profile (TFAP). We found that perturbagens of biological pathways elicited distinct TFAP signatures in human cells. Unexpectedly, perturbagens of the same pathway all produced identical TFAPs, regardless of where or how they interfered. We found invariant TFAPs for mitochondrial, histone deacetylase, and ubiquitin/proteasome pathway inhibitors; cytoskeleton disruptors; and DNA-damaging agents. Using these invariant signatures permitted straightforward identification of compounds with specified bioactivities among uncharacterized chemicals. Furthermore, this approach allowed us to assess the multiple bioactivities of polypharmacological drugs. Thus, TF activity profiling affords straightforward assessment of the bioactivity of compounds through the identification of perturbed biological pathways.

Indexed as

Biomarkers, TumorCarcinoma, HepatocellularCell ProliferationComputational BiologyDose-Response Relationship, DrugDrugs, InvestigationalGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLiver NeoplasmsTranscription FactorsTranscriptomeTumor Cells, CulturedBiomarkers, TumorDrugs, InvestigationalTranscription Factors

Identifiers

PMID30263952
PMCPMC6157966

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.