Evidence map›Paper›PMID 31637999›Full record

ArticleeLife2019

Improving drug discovery using image-based multiparametric analysis of the epigenetic landscape.

Chen Farhy, Santosh Hariharan, Jarkko Ylanko, Luis Orozco, Fu-Yue Zeng, Ian Pass, Fernando Ugarte, E Camilla Forsberg, Chun-Teng Huang, David W Andrews and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

19 citing papers in PubMed, 38 citations in OpenAlex.

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  14. Studying Chromatin Epigenetics with Fluorescence Microscopy.International journal of molecular sciences · 2022
    Review
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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

11 authors at 3 institutions in 2 countries.

Chen FarhySanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.ORCID 0000-0001-6160-3479
Santosh HariharanBiological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Ontario, Canada.
Jarkko YlankoBiological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Ontario, Canada.
Luis OrozcoSanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
Fu-Yue ZengSanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
Ian PassSanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
Fernando UgarteDepartment of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, United States.
E Camilla ForsbergDepartment of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, United States.
Chun-Teng HuangSanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
David W AndrewsBiological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Ontario, Canada.ORCID 0000-0002-9266-7157
Alexey V TerskikhSanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.ORCID 0000-0003-4641-3997
Sanford Burnham Prebys Medical Discovery Institute · USSunnybrook Health Science Centre · CAUniversity of California, Santa Cruz · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
Regulation of Chromatin Structure Dynamics in Hematopoietic and Leukemic Stem CelR01HL115158 · NHLBI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI FORSBERG, CAMILLA · 2013 to 2017
$2.1M
Role of MELK in glioblastomasR01NS066278 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI TERSKIKH, ALEXEY V · 2010 to 2014
$2.1M
NCI NIH HHS P30 CA030199NHLBI NIH HHS R01 HL115158NIH HHS R01 NS066278NINDS NIH HHS R01 NS066278
6 · The paper itself

Abstract

High-content phenotypic screening has become the approach of choice for drug discovery due to its ability to extract drug-specific multi-layered data. In the field of epigenetics, such screening methods have suffered from a lack of tools sensitive to selective epigenetic perturbations. Here we describe a novel approach, Microscopic Imaging of Epigenetic Landscapes (MIEL), which captures the nuclear staining patterns of epigenetic marks and employs machine learning to accurately distinguish between such patterns. We validated the MIEL platform across multiple cells lines and using dose-response curves, to insure the fidelity and robustness of this approach for high content high throughput drug discovery. Focusing on noncytotoxic glioblastoma treatments, we demonstrated that MIEL can identify and classify epigenetically active drugs. Furthermore, we show MIEL was able to accurately rank candidate drugs by their ability to produce desired epigenetic alterations consistent with increased sensitivity to chemotherapeutic agents or with induction of glioblastoma differentiation.

Indexed as

High-Throughput Screening AssaysAntineoplastic AgentsBiomarkers, TumorBrain NeoplasmsCell Line, TumorCell NucleusDose-Response Relationship, DrugDrug DiscoveryEpigenesis, GeneticGlioblastomaHistonesHumansImage Processing, Computer-AssistedMachine LearningMicroscopy, FluorescenceNeoplasm ProteinsAntineoplastic AgentsBiomarkers, TumorHistonesNeoplasm Proteinscancer biologyepigeneticsglioblastomahigh content screeninghumanhuman biologymedicine

Identifiers

PMID31637999
PMCPMC6908434
OpenAlexW2982103133

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.