{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:11:43Z","timestamp":1782745903441,"version":"3.54.5"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M011224\/1"],"award-info":[{"award-number":["BB\/M011224\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/S507593\/1"],"award-info":[{"award-number":["BB\/S507593\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>With ongoing development of the CRISPR\/Cas programmable nuclease system, applications in the area of in vivo therapeutic gene editing are increasingly within reach. However, non-negligible off-target effects remain a major concern for clinical applications. Even though a multitude of off-target cleavage datasets have been published, a comprehensive, transparent overview tool has not yet been established. Here, we present crisprSQL (http:\/\/www.crisprsql.com), an interactive and bioinformatically enhanced collection of CRISPR\/Cas9 off-target cleavage studies aimed at enriching the fields of cleavage profiling, gene editing safety analysis and transcriptomics. The current version of crisprSQL contains cleavage data from 144 guide RNAs on 25,632 guide-target pairs from human and rodent cell lines, with interaction-specific references to epigenetic markers and gene names. The first curated database of this standard, it promises to enhance safety quantification research, inform experiment design and fuel development of computational off-target prediction algorithms.<\/jats:p>","DOI":"10.1093\/nar\/gkaa885","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T19:10:08Z","timestamp":1602961808000},"page":"D855-D861","source":"Crossref","is-referenced-by-count":38,"title":["crisprSQL: a novel database platform for CRISPR\/Cas off-target cleavage assays"],"prefix":"10.1093","volume":"49","author":[{"given":"Florian","family":"St\u00f6rtz","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of Oxford, Parks Road, Oxford OX1 3QD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Minary","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Oxford, Parks Road, Oxford OX1 3QD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"2021010313113291000_B1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrd.2016.238","article-title":"Cornerstones of CRISPR-Cas in drug discovery and therapy","volume":"16","author":"Fellmann","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"2021010313113291000_B2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/bfgp\/elz031","article-title":"Advances in therapeutic application of CRISPR-Cas9","volume":"19","author":"Sun","year":"2020","journal-title":"Brief. Funct. Genomics"},{"key":"2021010313113291000_B3","doi-asserted-by":"crossref","first-page":"e349","DOI":"10.1038\/mtna.2016.58","article-title":"CRISPR-Cas9 for in vivo gene therapy: promise and hurdles","volume":"5","author":"Dai","year":"2016","journal-title":"Mol. Ther. - Nucleic Acids"},{"key":"2021010313113291000_B4","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00109-020-01893-z","article-title":"Mitigating off-target effects in CRISPR\/Cas9-mediated in vivo gene editing","volume":"98","author":"Han","year":"2020","journal-title":"J. Mol. Med."},{"key":"2021010313113291000_B5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/nat.2019.0790","article-title":"Evaluation and reduction of CRISPR Off-Target cleavage events","volume":"29","author":"Vakulskas","year":"2019","journal-title":"Nucleic Acid Ther."},{"key":"2021010313113291000_B6","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nbt.3117","article-title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","volume":"33","author":"Tsai","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2021010313113291000_B7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13059-018-1459-4","article-title":"DeepCRISPR: Optimized CRISPR guide RNA design by deep learning","volume":"19","author":"Chuai","year":"2018","journal-title":"Genome Biol."},{"key":"2021010313113291000_B8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12859-020-3395-z","article-title":"Deep learning improves the ability of sgRNA off-target propensity prediction","volume":"21","author":"Liu","year":"2020","journal-title":"BMC Bioinformatics"},{"key":"2021010313113291000_B9","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/bib\/bbz069","article-title":"Data imbalance in CRISPR off-target prediction","volume":"21","author":"Gao","year":"2020","journal-title":"Brief. Bioinform."},{"key":"2021010313113291000_B10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"Dunham","year":"2012","journal-title":"Nature"},{"key":"2021010313113291000_B11","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","article-title":"High frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells","volume":"31","author":"Fu","year":"2013","journal-title":"Nat. Biotechnol"},{"key":"2021010313113291000_B12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1101\/gr.162339.113","article-title":"Analysis of off-target effects of CRISPR\/Cas-derived RNA-guided endonucleases and nickases","volume":"24","author":"Cho","year":"2014","journal-title":"Genome Res."},{"key":"2021010313113291000_B13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nmeth.3284","article-title":"Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"2021010313113291000_B14","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature14299","article-title":"In vivo genome editing using Staphylococcus aureus Cas9","volume":"520","author":"Ran","year":"2015","journal-title":"Nature"},{"key":"2021010313113291000_B15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nbt.3101","article-title":"Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases","volume":"33","author":"Frock","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2021010313113291000_B16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nbt.3127","article-title":"Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors","volume":"33","author":"Wang","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2021010313113291000_B17","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1101\/gr.199588.115","article-title":"Genome-wide target specificities of CRISPR-Cas9 nucleases revealed by multiplex Digenome-seq","volume":"26","author":"Kim","year":"2016","journal-title":"Genome Res."},{"key":"2021010313113291000_B18","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"},{"key":"2021010313113291000_B19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aad5227","article-title":"Rationally engineered Cas9 nucleases with improved specificity","volume":"351","author":"Slaymaker","year":"2016","journal-title":"Science"},{"key":"2021010313113291000_B20","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nmeth.4278","article-title":"CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets","volume":"14","author":"Tsai","year":"2017","journal-title":"Nat. Methods"},{"key":"2021010313113291000_B21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature24268","article-title":"Enhanced proofreading governs CRISPR-Cas9 targeting accuracy","volume":"550","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"2021010313113291000_B22","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nmeth.4284","article-title":"Mapping the genomic landscape of CRISPR-Cas9 cleavage","volume":"14","author":"Cameron","year":"2017","journal-title":"Nat. Methods"},{"key":"2021010313113291000_B23","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1101\/gr.236620.118","article-title":"DIG-seq: a genome-wide CRISPR off-target profiling method using chromatin DNA","volume":"28","author":"Kim","year":"2018","journal-title":"Genome Res."},{"key":"2021010313113291000_B24","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41592-018-0011-5","article-title":"CRISPR off-target analysis in genetically engineered rats and mice","volume":"15","author":"Anderson","year":"2018","journal-title":"Nat. Methods"},{"key":"2021010313113291000_B25","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41551-017-0178-6","article-title":"Prediction of off-target activities for the end-to-end design of CRISPR guide RNAs","volume":"2","author":"Listgarten","year":"2018","journal-title":"Nat. Biomed. Eng."},{"key":"2021010313113291000_B26","doi-asserted-by":"crossref","DOI":"10.1038\/s41587-020-0646-5","article-title":"Massively parallel kinetic profiling of natural and engineered CRISPR nucleases","author":"Jones","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"2021010313113291000_B27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13059-016-1012-2","article-title":"Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR","volume":"17","author":"Haeussler","year":"2016","journal-title":"Genome Biol."},{"key":"2021010313113291000_B28","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nbt.2647","article-title":"DNA targeting specificity of RNA-guided Cas9 nucleases","volume":"31","author":"Hsu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2021010313113291000_B29","doi-asserted-by":"crossref","first-page":"2000047","DOI":"10.1002\/bies.202000047","article-title":"Cas9 cuts and consequences; detecting, predicting, and mitigating CRISPR\/Cas9 on- and off-target damage","volume":"47","author":"Newman","year":"2020","journal-title":"BioEssays"},{"key":"2021010313113291000_B30","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cbpa.2015.10.001","article-title":"How specific is CRISPR\/Cas9 really","volume":"29","author":"O\u2019Geen","year":"2015","journal-title":"Curr. Opin. Chem. Biol."},{"key":"2021010313113291000_B31","doi-asserted-by":"crossref","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021010313113291000_B32","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/s41586-020-2493-4","article-title":"Expanded encyclopaedias of DNA elements in the human and mouse genomes","volume":"583","author":"Moore","year":"2020","journal-title":"Nature"},{"key":"2021010313113291000_B33","doi-asserted-by":"crossref","first-page":"e1007480","DOI":"10.1371\/journal.pcbi.1007480","article-title":"Prediction of off-target specificity and cell-specific fitness of CRISPR-Cas System using attention boosted deep learning and network-based gene feature","volume":"15","author":"Liu","year":"2019","journal-title":"PLoS Comput. Biol."},{"key":"2021010313113291000_B34","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.csbj.2020.01.013","article-title":"C-RNNCrispr: Prediction of CRISPR\/Cas9 sgRNA activity using convolutional and recurrent neural networks","volume":"18","author":"Zhang","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"2021010313113291000_B35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1095\/biolreprod.114.122945","article-title":"The role of CCCTC-binding factor (CTCF) in genomic imprinting, development, and reproduction","volume":"91","author":"Franco","year":"2014","journal-title":"Biol. Reprod."},{"key":"2021010313113291000_B36","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.tig.2003.09.007","article-title":"Histone lysine methylation: a signature for chromatin function","volume":"19","author":"Sims","year":"2003","journal-title":"Trends Genet."},{"key":"2021010313113291000_B37","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1073\/pnas.1810409116","article-title":"DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells","volume":"116","author":"De\u00a0Magis","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021010313113291000_B38","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/bioinformatics\/bts277","article-title":"BEDOPS: high-performance genomic feature operations","volume":"28","author":"Neph","year":"2012","journal-title":"Bioinformatics"},{"key":"2021010313113291000_B39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13072-015-0040-6","article-title":"RNA:DNA hybrids in the human genome have distinctive nucleotide characteristics, chromatin composition, and transcriptional relationships","volume":"8","author":"Nadel","year":"2015","journal-title":"Epigenet. Chromatin"},{"key":"2021010313113291000_B40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.molcel.2016.05.032","article-title":"Prevalent, dynamic, and conserved R-Loop structures associate with specific epigenomic signatures in mammals","volume":"63","author":"Sanz","year":"2016","journal-title":"Mol. Cell"},{"key":"2021010313113291000_B41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature25748","article-title":"EWS-FLI1 increases transcription to cause R-Loops and block BRCA1 repair in Ewing sarcoma","volume":"555","author":"Gorthi","year":"2018","journal-title":"Nature"},{"key":"2021010313113291000_B42","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets-update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021010313113291000_B43","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/bioinformatics\/btr174","article-title":"BamTools: a C++ API and toolkit for analyzing and managing BAM files","volume":"27","author":"Barnett","year":"2011","journal-title":"Bioinformatics"},{"key":"2021010313113291000_B44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s13059-018-1534-x","article-title":"CRISPR-Cas9 off-targeting assessment with nucleic acid duplex energy parameters","volume":"19","author":"Alkan","year":"2018","journal-title":"Genome Biol."},{"key":"2021010313113291000_B45","doi-asserted-by":"crossref","first-page":"W70","DOI":"10.1093\/nar\/gkn188","article-title":"The Vienna RNA Websuite","volume":"36","author":"Gruber","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2021010313113291000_B46","doi-asserted-by":"crossref","first-page":"D679","DOI":"10.1093\/nar\/gkw997","article-title":"GenomeCRISPR - a database for high-throughput CRISPR\/Cas9 screens","volume":"45","author":"Rauscher","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021010313113291000_B47","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.1112178","article-title":"Genome-Scale identification of nucleosome positions in S. cerevisiae","volume":"309","author":"Yuan","year":"2005","journal-title":"Science"},{"key":"2021010313113291000_B48","doi-asserted-by":"crossref","first-page":"9351","DOI":"10.1073\/pnas.1810062115","article-title":"Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo","volume":"115","author":"Yarrington","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D855\/35364360\/gkaa885.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D855\/35364360\/gkaa885.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T18:12:49Z","timestamp":1609697569000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/D1\/D855\/5934413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,21]]},"references-count":48,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2020,10,21]]},"published-print":{"date-parts":[[2021,1,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa885","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,8]]},"published":{"date-parts":[[2020,10,21]]}}}