Evidence map›Paper›PMID 32441181›Full record

ArticleSLAS discovery : advancing life sciences R & D2020

High-Content Phenotypic Profiling in Esophageal Adenocarcinoma Identifies Selectively Active Pharmacological Classes of Drugs for Repurposing and Chemical Starting Points for Novel Drug Discovery.

Rebecca E Hughes, Richard J R Elliott, Alison F Munro, Ashraff Makda, J Robert O'Neill, Ted Hupp, Neil O Carragher

Abstract read
In one paragraph

Article in SLAS discovery : advancing life sciences R & D, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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  18. Nuisance compounds in cellular assays.Cell chemical biology · 2021
    Review
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

7 authors.

Rebecca E HughesMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.ORCID https://orcid.org/0000-0002-0590-4135
Richard J R ElliottMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
Alison F MunroMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
Ashraff MakdaMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
J Robert O'NeillCambridge Oesophagogastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK.
Ted HuppMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.
Neil O CarragherMRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK.

Funding

Cancer Research UK 24892Medical Research Council MR/K017047/1Medical Research Council MR/R015635/1
6 · The paper itself

Abstract

Esophageal adenocarcinoma (EAC) is a highly heterogeneous disease, dominated by large-scale genomic rearrangements and copy number alterations. Such characteristics have hampered conventional target-directed drug discovery and personalized medicine strategies, contributing to poor outcomes for patients. We describe the application of a high-content Cell Painting assay to profile the phenotypic response of 19,555 compounds across a panel of six EAC cell lines and two tissue-matched control lines. We built an automated high-content image analysis pipeline to identify compounds that selectively modified the phenotype of EAC cell lines. We further trained a machine-learning model to predict the mechanism of action of EAC selective compounds using phenotypic fingerprints from a library of reference compounds. We identified a number of phenotypic clusters enriched with similar pharmacological classes, including methotrexate and three other antimetabolites that are highly selective for EAC cell lines. We further identify a small number of hits from our diverse chemical library that show potent and selective activity for EAC cell lines and that do not cluster with the reference library of compounds, indicating they may be selectively targeting novel esophageal cancer biology. Overall, our results demonstrate that our EAC phenotypic screening platform can identify existing pharmacologic classes and novel compounds with selective activity for EAC cell phenotypes.

Indexed as

Drug RepositioningMolecular ImagingAdenocarcinomaCell Line, TumorDrug DiscoveryEsophageal NeoplasmsGene Expression ProfilingHumansMachine LearningPhenotypeSmall Molecule LibrariesSmall Molecule Librariesesophageal adenocarcinomahigh contentmachine learningmechanism of actionphenotypic

Identifiers

PMID32441181
PMCPMC7372582

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Registered trials

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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.