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GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases

Overview of attention for article published in Nature Biotechnology, December 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Citations

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Title
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Published in
Nature Biotechnology, December 2014
DOI 10.1038/nbt.3117
Pubmed ID
Authors

Shengdar Q Tsai, Zongli Zheng, Nhu T Nguyen, Matthew Liebers, Ved V Topkar, Vishal Thapar, Nicolas Wyvekens, Cyd Khayter, A John Iafrate, Long P Le, Martin J Aryee, J Keith Joung

Abstract

CRISPR RNA-guided nucleases (RGNs) are widely used genome-editing reagents, but methods to delineate their genome-wide, off-target cleavage activities have been lacking. Here we describe an approach for global detection of DNA double-stranded breaks (DSBs) introduced by RGNs and potentially other nucleases. This method, called genome-wide, unbiased identification of DSBs enabled by sequencing (GUIDE-seq), relies on capture of double-stranded oligodeoxynucleotides into DSBs. Application of GUIDE-seq to 13 RGNs in two human cell lines revealed wide variability in RGN off-target activities and unappreciated characteristics of off-target sequences. The majority of identified sites were not detected by existing computational methods or chromatin immunoprecipitation sequencing (ChIP-seq). GUIDE-seq also identified RGN-independent genomic breakpoint 'hotspots'. Finally, GUIDE-seq revealed that truncated guide RNAs exhibit substantially reduced RGN-induced, off-target DSBs. Our experiments define the most rigorous framework for genome-wide identification of RGN off-target effects to date and provide a method for evaluating the safety of these nucleases before clinical use.

X Demographics

X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 2,457 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 25 1%
Germany 7 <1%
United Kingdom 6 <1%
China 4 <1%
Denmark 3 <1%
Canada 3 <1%
Switzerland 2 <1%
Austria 2 <1%
Netherlands 2 <1%
Other 14 <1%
Unknown 2389 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 562 23%
Researcher 499 20%
Student > Bachelor 278 11%
Student > Master 246 10%
Other 105 4%
Other 308 13%
Unknown 459 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 794 32%
Agricultural and Biological Sciences 722 29%
Medicine and Dentistry 106 4%
Engineering 55 2%
Neuroscience 51 2%
Other 221 9%
Unknown 508 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 190. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 March 2024.
All research outputs
#209,294
of 25,405,598 outputs
Outputs from Nature Biotechnology
#427
of 8,557 outputs
Outputs of similar age
#2,225
of 360,810 outputs
Outputs of similar age from Nature Biotechnology
#5
of 97 outputs
Altmetric has tracked 25,405,598 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,557 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 44.3. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 360,810 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.