Evidence map›Paper›PMID 32029722›Full record

ArticleNature communications2020

Genetic screens in isogenic mammalian cell lines without single cell cloning.

Peter C DeWeirdt, Annabel K Sangree, Ruth E Hanna, Kendall R Sanson, Mudra Hegde, Christine Strand, Nicole S Persky, John G Doench

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
–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

91 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  19. Cul5bioRxiv : the preprint server for biology · 2025
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31 more citing papers are in PubMed but not listed here.

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

8 authors.

Peter C DeWeirdt *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.
Annabel K Sangree *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.
Ruth E Hanna *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.
Kendall R Sanson *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.
Mudra HegdeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-4530-4633
Christine StrandGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0001-5783-6667
Nicole S PerskyGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA, 02142, USA. jdoench@broadinstitute.org.ORCID http://orcid.org/0000-0002-3707-9889

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Isogenic pairs of cell lines, which differ by a single genetic modification, are powerful tools for understanding gene function. Generating such pairs of mammalian cells, however, is labor-intensive, time-consuming, and, in some cell types, essentially impossible. Here, we present an approach to create isogenic pairs of cells that avoids single cell cloning, and screen these pairs with genome-wide CRISPR-Cas9 libraries to generate genetic interaction maps. We query the anti-apoptotic genes BCL2L1 and MCL1, and the DNA damage repair gene PARP1, identifying both expected and uncharacterized buffering and synthetic lethal interactions. Additionally, we compare acute CRISPR-based knockout, single cell clones, and small-molecule inhibition. We observe that, while the approaches provide largely overlapping information, differences emerge, highlighting an important consideration when employing genetic screens to identify and characterize potential drug targets. We anticipate that this methodology will be broadly useful to comprehensively study gene function across many contexts.

Indexed as

Apoptosisbcl-X ProteinCell LineClone CellsCRISPR-Cas SystemsGene Knockout TechniquesGene LibraryGene Regulatory NetworksGenetic TestingHumansMultigene FamilyMyeloid Cell Leukemia Sequence 1 ProteinPoly (ADP-Ribose) Polymerase-1Single-Cell AnalysisBCL2L1 protein, humanbcl-X ProteinMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1

Identifiers

PMID32029722
PMCPMC7005275

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.