Evidence map›Paper›PMID 28459458›Full record

ArticleNature methods2017

CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets.

Shengdar Q Tsai, Nhu T Nguyen, Jose Malagon-Lopez, Ved V Topkar, Martin J Aryee, J Keith Joung

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 498 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
498citing papers in PubMed, 2 pooled it
34.8field-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

498 citing papers in PubMed, 2 syntheses or guidelines pooled it, 801 citations in OpenAlex.

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438 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Shengdar Q TsaiMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Nhu T NguyenMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Jose Malagon-LopezMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Ved V TopkarMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Martin J AryeeMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.ORCID http://orcid.org/0000-0002-6848-1344
J Keith JoungMolecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Harvard University · USMassachusetts General Hospital · US

Funding

Evolution, Optimization, and Application of Genome Editing TechnologiesR35GM118158 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2016 to 2023
$4.7M
Advancing stem cell technologies using engineered zinc finger proteinsDP1GM105378 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2012 to 2014
$2.6M
Utilizing genetic and functional strategies to identify causal genes and allelesR01GM107427 · NIGMS · DANA-FARBER CANCER INST · PI FREEDMAN, MATTHEW L, JOUNG, J. KEITH · 2014 to 2017
$2.0M
NIGMS NIH HHS DP1 GM105378NIGMS NIH HHS R01 GM107427NIGMS NIH HHS R35 GM118158
6 · The paper itself

Abstract

Sensitive detection of off-target effects is important for translating CRISPR-Cas9 nucleases into human therapeutics. In vitro biochemical methods for finding off-targets offer the potential advantages of greater reproducibility and scalability while avoiding limitations associated with strategies that require the culture and manipulation of living cells. Here we describe circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), a highly sensitive, sequencing-efficient in vitro screening strategy that outperforms existing cell-based or biochemical approaches for identifying CRISPR-Cas9 genome-wide off-target mutations. In contrast to previously described in vitro methods, we show that CIRCLE-seq can be practiced using widely accessible next-generation sequencing technology and does not require reference genome sequences. Importantly, CIRCLE-seq can be used to identify off-target mutations associated with cell-type-specific single-nucleotide polymorphisms, demonstrating the feasibility and importance of generating personalized specificity profiles. CIRCLE-seq provides an accessible, rapid, and comprehensive method for identifying genome-wide off-target mutations of CRISPR-Cas9.

Indexed as

Chromosome MappingClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDeoxyribonucleasesGenomeHigh-Throughput Nucleotide SequencingReproducibility of ResultsSensitivity and SpecificitySequence Analysis, DNADeoxyribonucleases

Identifiers

PMID28459458
PMCPMC5924695
OpenAlexW2611661371

What OpenQuestion holds

Textmetadata
LicenceTDM
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.