Evidence map›Paper›PMID 38678031›Full record

ArticleNature communications2024

Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform.

Nazanin Esmaeili Anvar, Chenchu Lin, Xingdi Ma, Lori L Wilson, Ryan Steger, Annabel K Sangree, Medina Colic, Sidney H Wang, John G Doench, Traver Hart

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
14.3field-weighted citation impact, top 1% 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

46 citing papers in PubMed, 59 citations in OpenAlex.

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  11. Proximity labeling of thebioRxiv : the preprint server for biology · 2026
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  15. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Nazanin Esmaeili Anvar *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7672-8178
Chenchu Lin *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xingdi Ma *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lori L WilsonDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ryan StegerGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Annabel K SangreeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Medina ColicDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sidney H WangCenter for Human Genetics, The Brown foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3707-9889
Traver HartDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. traver@hart-lab.org.ORCID http://orcid.org/0000-0002-1880-3341
The University of Texas MD Anderson Cancer Center · USBroad Institute · USCenter for Human Genetics · US

Funding

Identifying and targeting collateral lethal vulnerabilities in cancersU01CA275886 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RONALD ANTHONY DEPINHO, Traver Hart · 2023 to 2026
$3.9M
High-content microscopy platform for multiplex perturbation/multiplex readout studiesR35GM130119 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Traver Hart · 2018 to 2026
$3.9M
Expanding the known coding genome: identifying biological function for novel tORFsR01GM139980 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI WANG, SIDNEY · 2021 to 2025
$1.5M
NCI NIH HHS U01 CA275886NIGMS NIH HHS R01 GM139980NIGMS NIH HHS R35 GM130119
6 · The paper itself

Abstract

Genetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale. Here, we identify background-independent paralog synthetic lethals from previous CRISPR genetic interaction screens, and find that the Cas12a platform provides superior sensitivity and assay replicability. We develop the in4mer Cas12a platform that uses arrays of four independent guide RNAs targeting the same or different genes. We construct a genome-scale library, Inzolia, that is ~30% smaller than a typical CRISPR/Cas9 library while also targeting ~4000 paralog pairs. Screens in cancer cells demonstrate discrimination of core and context-dependent essential genes similar to that of CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes. Importantly, the in4mer platform offers a fivefold reduction in library size compared to other genetic interaction methods, substantially reducing the cost and effort required for these assays.

Indexed as

Bacterial ProteinsCRISPR-Cas SystemsEndodeoxyribonucleasesGene Knockout TechniquesCell Line, TumorCRISPR-Associated ProteinsEpistasis, GeneticGene LibraryGenes, EssentialHEK293 CellsHumansRNA, Guide, CRISPR-Cas SystemsBacterial ProteinsCas12a proteinCRISPR-Associated ProteinsEndodeoxyribonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID38678031
PMCPMC11055879
OpenAlexW4395695320

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.