{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:30:58Z","timestamp":1791415858387,"version":"4.3.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T00:00:00Z","timestamp":1478736000000},"content-version":"vor","delay-in-days":73,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004807","name":"DFG","doi-asserted-by":"publisher","award":["FOR1680"],"award-info":[{"award-number":["FOR1680"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Unravelling the Prokaryotic Immune System","award":["BA 2168\/5-1"],"award-info":[{"award-number":["BA 2168\/5-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The CRISPR-Cas system is an adaptive immune system in many archaea and bacteria, which provides resistance against invading genetic elements. The first phase of CRISPR-Cas immunity is called adaptation, in which small DNA fragments are excised from genetic elements and are inserted into a CRISPR array generally adjacent to its so called leader sequence at one end of the array. It has been shown that transcription initiation and adaptation signals of the CRISPR array are located within the leader. However, apart from promoters, there is very little knowledge of sequence or structural motifs or their possible functions. Leader properties have mainly been characterized through transcriptional initiation data from single organisms but large-scale characterization of leaders has remained challenging due to their low level of sequence conservation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We developed a method to successfully detect leader sequences by focusing on the consensus repeat of the adjacent CRISPR array and weak upstream conservation signals. We applied our tool to the analysis of a comprehensive genomic database and identified several characteristic properties of leader sequences specific to archaea and bacteria, ranging from distinctive sizes to preferential indel localization. CRISPRleader provides a full annotation of the CRISPR array, its strand orientation as well as conserved core leader boundaries that can be uploaded to any genome browser. In addition, it outputs reader-friendly HTML pages for conserved leader clusters from our database.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>CRISPRleader and multiple sequence alignments for all 195 leader clusters are available at http:\/\/www.bioinf.uni-freiburg.de\/Software\/CRISPRleader\/.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Contact<\/jats:title>\n                  <jats:p>costa@informatik.uni-freiburg.de or backofen@informatik.uni-freiburg.de<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btw454","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T07:53:39Z","timestamp":1472716419000},"page":"i576-i585","source":"Crossref","is-referenced-by-count":87,"title":["Characterizing leader sequences of CRISPR loci"],"prefix":"10.1093","volume":"32","author":[{"given":"Omer S","family":"Alkhnbashi","sequence":"first","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiraz A","family":"Shah","sequence":"additional","affiliation":[{"name":"Archaea Centre, Department of Biology, University of Copenhagen N, DK2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A","family":"Garrett","sequence":"additional","affiliation":[{"name":"Archaea Centre, Department of Biology, University of Copenhagen N, DK2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita J","family":"Saunders","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Costa","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science, University of Freiburg, 79110 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Backofen","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science, University of Freiburg, 79110 Freiburg, Germany"},{"name":"BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Freiburg im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,29]]},"reference":[{"key":"2023020113332080800_btw454-B1","doi-asserted-by":"crossref","first-page":"i489","DOI":"10.1093\/bioinformatics\/btu459","article-title":"CRISPRstrand: predicting repeat orientations to determine the crRNA-encoding strand at CRISPR loci","volume":"30","author":"Alkhnbashi","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020113332080800_btw454-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-34657-6","volume-title":"CRISPR-Cas Systems: RNA-Mediated Adaptive Immunity in Bacteria and Archaea","author":"Barrangou","year":"2013"},{"key":"2023020113332080800_btw454-B3","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.1159689","article-title":"Small CRISPR RNAs guide antiviral defense in prokaryotes","volume":"321","author":"Brouns","year":"2008","journal-title":"Science"},{"key":"2023020113332080800_btw454-B4","first-page":"255","author":"Costa","year":"2010"},{"key":"2023020113332080800_btw454-B5","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1093\/nar\/gkr1111","article-title":"Modulation of CRISPR locus transcription by the repeat-binding protein Cbp1 in Sulfolobus","volume":"40","author":"Deng","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023020113332080800_btw454-B6","doi-asserted-by":"crossref","first-page":"792","DOI":"10.4161\/rna.24023","article-title":"CRISPR-spacer integration reporter plasmids reveal distinct genuine acquisition specificities among CRISPR-Cas I\u2013E variants of Escherichia coli","volume":"10","author":"Diez-Villasenor","year":"2013","journal-title":"RNA Biol"},{"key":"2023020113332080800_btw454-B7","doi-asserted-by":"crossref","first-page":"e1002195.","DOI":"10.1371\/journal.pcbi.1002195","article-title":"Accelerated profile HMM searches","volume":"7","author":"Eddy","year":"2011","journal-title":"PLoS Comput. 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