Evidence map›Paper›PMID 38811841›Full record

ArticleNature genetics2024

High-resolution genome-wide mapping of chromosome-arm-scale truncations induced by CRISPR-Cas9 editing.

Nathan H Lazar, Safiye Celik, Lu Chen, Marta M Fay, Jonathan C Irish, James Jensen, Conor A Tillinghast, John Urbanik, William P Bone, Christopher C Gibson and 1 more

Abstract read
In one paragraph

Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

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  14. Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
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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.

Nathan H LazarRecursion, Salt Lake City, UT, USA.
Safiye CelikRecursion, Salt Lake City, UT, USA.
Lu ChenRecursion, Salt Lake City, UT, USA.
Marta M FayRecursion, Salt Lake City, UT, USA.
Jonathan C IrishRecursion, Salt Lake City, UT, USA.
James JensenRecursion, Salt Lake City, UT, USA.
Conor A TillinghastRecursion, Salt Lake City, UT, USA.
John UrbanikRecursion, Salt Lake City, UT, USA.
William P BoneRecursion, Salt Lake City, UT, USA.
Christopher C GibsonRecursion, Salt Lake City, UT, USA.
Imran S HaqueRecursion, Salt Lake City, UT, USA. Imran.Haque@recursionpharma.com.ORCID http://orcid.org/0000-0001-7782-2852

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is a powerful tool for introducing targeted mutations in DNA, but recent studies have shown that it can have unintended effects such as structural changes. However, these studies have not yet looked genome wide or across data types. Here we performed a phenotypic CRISPR-Cas9 scan targeting 17,065 genes in primary human cells, revealing a 'proximity bias' in which CRISPR knockouts show unexpected similarities to unrelated genes on the same chromosome arm. This bias was found to be consistent across cell types, laboratories, Cas9 delivery methods and assay modalities, and the data suggest that it is caused by telomeric truncations of chromosome arms, with cell cycle and apoptotic pathways playing a mediating role. Additionally, a simple correction is demonstrated to mitigate this pervasive bias while preserving biological relationships. This previously uncharacterized effect has implications for functional genomic studies using CRISPR-Cas9, with applications in discovery biology, drug-target identification, cell therapies and genetic therapeutics.

Indexed as

CRISPR-Cas SystemsGene EditingChromosome MappingGenome, HumanHumans

Identifiers

PMID38811841
PMCPMC11250378

What Socratic 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 Socratic graph.