{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:20:28Z","timestamp":1790176828841,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["390939984"],"award-info":[{"award-number":["390939984"]}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["BA 2168\/11-1"],"award-info":[{"award-number":["BA 2168\/11-1"]}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["SPP 1738"],"award-info":[{"award-number":["SPP 1738"]}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["BA2168\/11-2 SPP 1738"],"award-info":[{"award-number":["BA2168\/11-2 SPP 1738"]}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["BA 2168\/3-3"],"award-info":[{"award-number":["BA 2168\/3-3"]}]},{"name":"Germany\u2019s Excellence Strategy\u2014EXC-2189\u2014Project","award":["GRK 2344\/1 2017"],"award-info":[{"award-number":["GRK 2344\/1 2017"]}]},{"name":"MeInBio"},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2013\/07375-0"],"award-info":[{"award-number":["2013\/07375-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2019\/21300-9"],"award-info":[{"award-number":["2019\/21300-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>CRISPR-Cas are important systems found in most archaeal and many bacterial genomes, providing adaptive immunity against mobile genetic elements in prokaryotes. The CRISPR-Cas systems are encoded by a set of consecutive cas genes, here termed cassette. The identification of cassette boundaries is key for finding cassettes in CRISPR research field. This is often carried out by using Hidden Markov Models and manual annotation. In this article, we propose the first method able to automatically define the cassette boundaries. In addition, we present a Cas-type predictive model used by the method to assign each gene located in the region defined by a cassette\u2019s boundaries a Cas label from a set of pre-defined Cas types. Furthermore, the proposed method can detect potentially new cas genes and decompose a cassette into its modules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We evaluate the predictive performance of our proposed method on data collected from the two most recent CRISPR classification studies. In our experiments, we obtain an average similarity of 0.86 between the predicted and expected cassettes. Besides, we achieve F-scores above 0.9 for the classification of cas genes of known types and 0.73 for the unknown ones. Finally, we conduct two additional study cases, where we investigate the occurrence of potentially new cas genes and the occurrence of module exchange between different genomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>https:\/\/github.com\/BackofenLab\/Casboundary.<\/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\/btaa984","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T15:18:22Z","timestamp":1605107902000},"page":"1352-1359","source":"Crossref","is-referenced-by-count":14,"title":["Casboundary: automated definition of integral Cas cassettes"],"prefix":"10.1093","volume":"37","author":[{"given":"Victor A","family":"Padilha","sequence":"first","affiliation":[{"name":"Institute of Mathematics and Computer Sciences, University of S\u00e3o Paulo , S\u00e3o Carlos, SP 13566-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8088-590X","authenticated-orcid":false,"given":"Omer S","family":"Alkhnbashi","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science, University of Freiburg , 79110 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-4959","authenticated-orcid":false,"given":"Van Dinh","family":"Tran","sequence":"additional","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":"COPSAC, Copenhagen University Hospitals Herlev and Gentofte , DK-2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 C P L F","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Mathematics and Computer Sciences, University of S\u00e3o Paulo , S\u00e3o Carlos, SP 13566-590, Brazil"}],"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":"Signalling Research Centres BIOSS and CIBSS, University of Freiburg , 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,6]]},"reference":[{"key":"2023051709254030600_btaa984-B1","doi-asserted-by":"crossref","first-page":"i576","DOI":"10.1093\/bioinformatics\/btw454","article-title":"Characterizing leader sequences of crispr loci","volume":"32","author":"Alkhnbashi","year":"2016","journal-title":"Bioinformatics"},{"key":"2023051709254030600_btaa984-B2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2019.07.013","article-title":"CRISPR-cas bioinformatics","volume":"172","author":"Alkhnbashi","year":"2020","journal-title":"Methods"},{"key":"2023051709254030600_btaa984-B3","first-page":"i489","article-title":"CRISPRstrand: predicting repeat orientations to determine the crRNA-encoding strand at CRISPR loci","volume":"30","author":"Alkhnbashi","year":"2014","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023051709254030600_btaa984-B4","doi-asserted-by":"crossref","first-page":"D138","DOI":"10.1093\/nar\/gkh121","article-title":"The pfam protein families database","volume":"32","author":"Bateman","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B5","doi-asserted-by":"crossref","first-page":"W246","DOI":"10.1093\/nar\/gky425","article-title":"CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins","volume":"46","author":"Couvin","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1089\/crispr.2017.0022","article-title":"CRISPRdisco: an automated pipeline for the discovery and analysis of CRISPR-cas systems","volume":"1","author":"Crawley","year":"2018","journal-title":"CRISPR J"},{"key":"2023051709254030600_btaa984-B7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.tim.2011.08.002","article-title":"Archaeal CRISPR-based immune systems: exchangeable functional modules","volume":"19","author":"Garrett","year":"2011","journal-title":"Trends Microbiol"},{"key":"2023051709254030600_btaa984-B8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10994-006-6226-1","article-title":"Extremely randomized trees","volume":"63","author":"Geurts","year":"2006","journal-title":"Mach. Learn"},{"key":"2023051709254030600_btaa984-B9","volume-title":"Deep Learning","author":"Goodfellow","year":"2016"},{"key":"2023051709254030600_btaa984-B10","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1371\/journal.pcbi.0010060","article-title":"A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR\/Cas subtypes exist in prokaryotic genomes","volume":"1","author":"Haft","year":"2005","journal-title":"PLoS Comput. Biol"},{"key":"2023051709254030600_btaa984-B11","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/nar\/gkg128","article-title":"The tigrfams database of protein families","volume":"31","author":"Haft","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B12","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.cell.2009.07.040","article-title":"RNA-guided RNA cleavage by a CRISPR RNA-cas protein complex","volume":"139","author":"Hale","year":"2009","journal-title":"Cell"},{"key":"2023051709254030600_btaa984-B13","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/JB.01415-07","article-title":"Diversity, activity, and evolution of crispr loci in streptococcus thermophilus","volume":"190","author":"Horvath","year":"2008","journal-title":"J. Bacteriol"},{"key":"2023051709254030600_btaa984-B14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/1471-2105-11-119","article-title":"Prodigal: prokaryotic gene recognition and translation initiation site identification","volume":"11","author":"Hyatt","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023051709254030600_btaa984-B15","author":"Kingma","year":"2015"},{"key":"2023051709254030600_btaa984-B16","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41576-019-0172-9","article-title":"Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire","volume":"21","author":"Koonin","year":"2020","journal-title":"Nature Reviews Genetics"},{"key":"2023051709254030600_btaa984-B17","doi-asserted-by":"crossref","first-page":"8034","DOI":"10.1093\/nar\/gkt606","article-title":"CRISPRmap: an automated classification of repeat conservation in prokaryotic adaptive immune systems","volume":"41","author":"Lange","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neucom.2016.12.038","article-title":"A survey of deep neural network architectures and their applications","volume":"234","author":"Liu","year":"2017","journal-title":"Neurocomputing"},{"key":"2023051709254030600_btaa984-B19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrmicro2577","article-title":"Evolution and classification of the CRISPR-Cas systems","volume":"9","author":"Makarova","year":"2011","journal-title":"Nat. Rev. Microbiol"},{"key":"2023051709254030600_btaa984-B20","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrmicro3569","article-title":"An updated evolutionary classification of CRISPR-Cas systems","volume":"13","author":"Makarova","year":"2015","journal-title":"Nat. Rev. Microbiol"},{"key":"2023051709254030600_btaa984-B21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41579-019-0299-x","article-title":"Evolutionary classification of CRISPR\u2013Cas systems: a burst of class 2 and derived variants","volume":"18","author":"Makarova","year":"2020","journal-title":"Nature Reviews Microbiology"},{"key":"2023051709254030600_btaa984-B22","volume-title":"Introduction to Information Retrieval","author":"Manning","year":"2009"},{"key":"2023051709254030600_btaa984-B23","doi-asserted-by":"crossref","first-page":"D225","DOI":"10.1093\/nar\/gkq1189","article-title":"Cdd: a conserved domain database for the functional annotation of proteins","volume":"39","author":"Marchler-Bauer","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B24","doi-asserted-by":"crossref","first-page":"giaa062","DOI":"10.1093\/gigascience\/giaa062","article-title":"Crisprcasidentifier: machine learning for accurate identification and classification of CRISPR-Cas systems","volume":"9","author":"Padilha","year":"2020","journal-title":"GigaScience"},{"key":"2023051709254030600_btaa984-B25","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1128\/JB.00206-12","article-title":"Characterization of the CRISPR\/Cas subtype I\u2014a system of the hyperthermophilic crenarchaeon thermoproteus tenax","volume":"194","author":"Plagens","year":"2012","journal-title":"J. Bacteriol"},{"key":"2023051709254030600_btaa984-B26","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nmeth.1818","article-title":"Hhblits: lightning-fast iterative protein sequence searching by hmm-hmm alignment","volume":"9","author":"Remmert","year":"2012","journal-title":"Nat. Methods"},{"key":"2023051709254030600_btaa984-B27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.resmic.2010.09.001","article-title":"CRISPR\/cas and cmr modules, mobility and evolution of adaptive immune systems","volume":"162","author":"Shah","year":"2011","journal-title":"Res. Microbiol"},{"key":"2023051709254030600_btaa984-B28","first-page":"1","article-title":"Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-Cas gene cassettes reveals 39 new cas gene families","volume":"0","author":"Shah","year":"2018","journal-title":"RNA Biol"},{"key":"2023051709254030600_btaa984-B29","first-page":"2911","author":"Shu","year":"2017"},{"key":"2023051709254030600_btaa984-B30","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ipm.2009.03.002","article-title":"A systematic analysis of performance measures for classification tasks","volume":"45","author":"Sokolova","year":"2009","journal-title":"Inf. Process. Manag"},{"key":"2023051709254030600_btaa984-B31","doi-asserted-by":"crossref","first-page":"16205","DOI":"10.1038\/nmicrobiol.2016.205","article-title":"Environmental microbiology: viral diversity on the global stage","volume":"1","author":"Suttle","year":"2016","journal-title":"Nat. Microbiol"},{"key":"2023051709254030600_btaa984-B32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/nar\/28.1.33","article-title":"The cog database: a tool for genome-scale analysis of protein functions and evolution","volume":"28","author":"Tatusov","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B33","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4161\/rna.27990","article-title":"CRISPR adaptive immune systems of archaea","volume":"11","author":"Vestergaard","year":"2014","journal-title":"RNA Biol"},{"key":"2023051709254030600_btaa984-B34","doi-asserted-by":"crossref","first-page":"10848","DOI":"10.1093\/nar\/gkv1261","article-title":"Foreign DNA acquisition by the I-F CRISPR\u2013Cas system requires all components of the interference machinery","volume":"43","author":"Vorontsova","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023051709254030600_btaa984-B35","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.molcel.2012.03.018","article-title":"CRISPR Immunity Relies on the Consecutive Binding and Degradation of Negatively Supercoiled Invader DNA by Cascade and Cas3","volume":"46","author":"Westra","year":"2012","journal-title":"Molecular Cell"},{"issue":"1","key":"2023051709254030600_btaa984-B36","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-017-1512-4","article-title":"Not all predicted CRISPR\u2013Cas systems are equal: isolated cas genes and classes of crispr like elements","volume":"18","author":"Zhang","year":"2017","journal-title":"BMC Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa984\/34731477\/btaa984.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/10\/1352\/50361051\/btaa984.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/10\/1352\/50361051\/btaa984.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T05:42:12Z","timestamp":1684302132000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/10\/1352\/5998667"}},"subtitle":[],"editor":[{"given":"Robinson","family":"Peter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,6]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,6,16]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa984","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,15]]},"published":{"date-parts":[[2020,12,6]]}}}