Evidence map›Paper›PMID 35176052›Full record

ArticlePloS one2022

Considerations and practical implications of performing a phenotypic CRISPR/Cas survival screen.

Ator Ashoti, Francesco Limone, Melissa van Kranenburg, Anna Alemany, Mirna Baak, Judith Vivié, Frederica Piccioni, Pascale F Dijkers, Menno Creyghton, Kevin Eggan and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 43% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

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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 2 institutions in 2 countries.

Ator AshotiHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Francesco LimoneDepartment of Stem Cell and Regenerative Biology, Harvard University Cambridge, MA, United States of America.
Melissa van KranenburgHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Anna AlemanyHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Mirna BaakHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Judith ViviéHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Frederica PiccioniBroad Institute, Cambridge, MA, United States of America.ORCID 0000-0003-1210-3210
Pascale F DijkersHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Menno CreyghtonHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.
Kevin EgganDepartment of Stem Cell and Regenerative Biology, Harvard University Cambridge, MA, United States of America.
Niels GeijsenHubrecht Institute, Developmental Biology and Stem Cell Research, Utrecht, The Netherlands.ORCID 0000-0003-3592-4353
Hubrecht Institute for Developmental Biology and Stem Cell Research · NLBroad Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genome-wide screens that have viability as a readout have been instrumental to identify essential genes. The development of gene knockout screens with the use of CRISPR-Cas has provided a more sensitive method to identify these genes. Here, we performed an exhaustive genome-wide CRISPR/Cas9 phenotypic rescue screen to identify modulators of cytotoxicity induced by the pioneer transcription factor, DUX4. Misexpression of DUX4 due to a failure in epigenetic repressive mechanisms underlies facioscapulohumeral muscular dystrophy (FHSD), a complex muscle disorder that thus far remains untreatable. As the name implies, FSHD generally starts in the muscles of the face and shoulder girdle. Our CRISPR/Cas9 screen revealed no key effectors other than DUX4 itself that could modulate DUX4 cytotoxicity, suggesting that treatment efforts in FSHD should be directed towards direct modulation of DUX4 itself. Our screen did however reveal some rare and unexpected genomic events, that had an important impact on the interpretation of our data. Our findings may provide important considerations for planning future CRISPR/Cas9 phenotypic survival screens.

Indexed as

CRISPR-Cas SystemsGene Expression RegulationCell SurvivalHomeodomain ProteinsHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMuscle CellsMuscular Dystrophy, FacioscapulohumeralMyoblastsDUX4L1 protein, humanHomeodomain Proteins

Identifiers

PMID35176052
PMCPMC8853573
OpenAlexW4213377066

What OpenQuestion holds

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LicenceCC BY
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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.