iGUIDE: an improved pipeline for analyzing CRISPR cleavage specificity
Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming...
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          | Published in | Genome Biology Vol. 20; no. 1; p. 14 | 
|---|---|
| Main Authors | , , , , , , , , | 
| Format | Journal Article | 
| Language | English | 
| Published | 
        London
          BioMed Central
    
        17.01.2019
     Springer Nature B.V BMC  | 
| Subjects | |
| Online Access | Get full text | 
| ISSN | 1474-760X 1474-7596 1474-760X  | 
| DOI | 10.1186/s13059-019-1625-3 | 
Cover
| Abstract | Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from
https://github.com/cnobles/iGUIDE
. | 
    
|---|---|
| AbstractList | Abstract Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE. Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE . Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE . Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE .Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE .  | 
    
| ArticleNumber | 14 | 
    
| Author | Nobles, Christopher L. Davis, Megan M. Salas-McKee, January Liu, Xiaojun Reddy, Shantan Zhao, Yangbing June, Carl H. Melenhorst, J. Joseph Bushman, Frederic D.  | 
    
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| Cites_doi | 10.1083/jcb.201312078 10.1158/1078-0432.CCR-16-1300 10.3390/ijms150713111 10.5281/zenodo.2531901 10.1038/nature10177 10.1038/nbt.3117 10.1182/blood-2010-08-302729 10.1371/journal.pgen.1005438 10.1186/s13059-019-1625-3 10.1038/nbt.1948 10.1073/pnas.2135498100 10.1038/nm1329 10.1038/nmeth.3284 10.1038/nmeth.2408 10.1016/j.cell.2011.07.048 10.1101/gr.146357.112 10.1038/s41586-018-0178-z 10.1038/nbt.3127 10.1016/S0092-8674(02)00864-4 10.1016/j.cell.2014.11.014 10.5281/zenodo.2538220 10.1016/j.stem.2014.04.020 10.1016/j.cell.2013.01.006 10.1016/j.cell.2011.07.049 10.1371/journal.pbio.0020234  | 
    
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| References | SQ Tsai (1625_CR7) 2015; 33 J Ren (1625_CR16) 2017; 23 M Ensminger (1625_CR18) 2014; 206 RS Mitchell (1625_CR24) 2004; 2 1625_CR19 R Chiarle (1625_CR8) 2011; 147 L Khair (1625_CR2) 2015; 11 ZX Zhou (1625_CR5) 2013; 23 A Veres (1625_CR13) 2014; 15 H Li (1625_CR14) 2011; 475 MM Vilenchik (1625_CR17) 2003; 100 L Baranello (1625_CR6) 2014; 15 R Gabriel (1625_CR10) 2011; 29 JH Barlow (1625_CR4) 2013; 152 H Li (1625_CR15) 2011; 117 D Kim (1625_CR3) 2015; 12 FL Meng (1625_CR11) 2014; 159 IA Klein (1625_CR12) 2011; 147 A Ciuffi (1625_CR25) 2005; 11 X Wang (1625_CR9) 2015; 33 AR Schroder (1625_CR23) 2002; 110 N Crosetto (1625_CR1) 2013; 10 1625_CR22 1625_CR21 1625_CR20  | 
    
| References_xml | – volume: 206 start-page: 29 year: 2014 ident: 1625_CR18 publication-title: J Cell Biol doi: 10.1083/jcb.201312078 – volume: 23 start-page: 2255 year: 2017 ident: 1625_CR16 publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-16-1300 – volume: 15 start-page: 13111 year: 2014 ident: 1625_CR6 publication-title: Int J Mol Sci doi: 10.3390/ijms150713111 – ident: 1625_CR21 doi: 10.5281/zenodo.2531901 – volume: 475 start-page: 217 year: 2011 ident: 1625_CR14 publication-title: Nature doi: 10.1038/nature10177 – volume: 33 start-page: 187 year: 2015 ident: 1625_CR7 publication-title: Nat Biotechnol doi: 10.1038/nbt.3117 – volume: 117 start-page: 3311 year: 2011 ident: 1625_CR15 publication-title: Blood doi: 10.1182/blood-2010-08-302729 – volume: 11 year: 2015 ident: 1625_CR2 publication-title: PLoS Genet doi: 10.1371/journal.pgen.1005438 – ident: 1625_CR19 doi: 10.1186/s13059-019-1625-3 – volume: 29 start-page: 816 year: 2011 ident: 1625_CR10 publication-title: Nat Biotechnol doi: 10.1038/nbt.1948 – volume: 100 start-page: 12871 year: 2003 ident: 1625_CR17 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.2135498100 – volume: 11 start-page: 1287 year: 2005 ident: 1625_CR25 publication-title: Nat Med doi: 10.1038/nm1329 – volume: 12 start-page: 237 year: 2015 ident: 1625_CR3 publication-title: Nat Methods doi: 10.1038/nmeth.3284 – volume: 10 start-page: 361 year: 2013 ident: 1625_CR1 publication-title: Nat Methods doi: 10.1038/nmeth.2408 – volume: 147 start-page: 95 year: 2011 ident: 1625_CR12 publication-title: Cell doi: 10.1016/j.cell.2011.07.048 – volume: 23 start-page: 705 year: 2013 ident: 1625_CR5 publication-title: Genome Res doi: 10.1101/gr.146357.112 – ident: 1625_CR22 doi: 10.1038/s41586-018-0178-z – volume: 33 start-page: 175 year: 2015 ident: 1625_CR9 publication-title: Nat Biotechnol doi: 10.1038/nbt.3127 – volume: 110 start-page: 521 year: 2002 ident: 1625_CR23 publication-title: Cell doi: 10.1016/S0092-8674(02)00864-4 – volume: 159 start-page: 1538 year: 2014 ident: 1625_CR11 publication-title: Cell doi: 10.1016/j.cell.2014.11.014 – ident: 1625_CR20 doi: 10.5281/zenodo.2538220 – volume: 15 start-page: 27 year: 2014 ident: 1625_CR13 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2014.04.020 – volume: 152 start-page: 620 year: 2013 ident: 1625_CR4 publication-title: Cell doi: 10.1016/j.cell.2013.01.006 – volume: 147 start-page: 107 year: 2011 ident: 1625_CR8 publication-title: Cell doi: 10.1016/j.cell.2011.07.049 – volume: 2 start-page: E234 year: 2004 ident: 1625_CR24 publication-title: PLoS Biol doi: 10.1371/journal.pbio.0020234  | 
    
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| Snippet | Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites... Abstract Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target...  | 
    
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| SubjectTerms | Animal Genetics and Genomics Binding sites Bioinformatics Biomedical and Life Sciences Chromatin Clustered Regularly Interspaced Short Palindromic Repeats CRISPR Deoxyribonucleic acid Design DNA DNA damage Evolutionary Biology Fragile sites genes Genetic Engineering - methods Genome editing Genomes Human Genetics Immunotherapy Insights from Genome Editing Life Sciences Lymphocytes Methods Microbial Genetics and Genomics Nuclease nucleases Plant Genetics and Genomics Short Report Software Stem cells T cell receptors  | 
    
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| Title | iGUIDE: an improved pipeline for analyzing CRISPR cleavage specificity | 
    
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