{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:26:04Z","timestamp":1768969564582,"version":"3.49.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health R01","doi-asserted-by":"crossref","award":["HG009626"],"award-info":[{"award-number":["HG009626"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>In recent years, multiple circular RNAs (circRNA) biogenesis mechanisms have been discovered. Although each reported mechanism has been experimentally verified in different circRNAs, no single biogenesis mechanism has been proposed that can universally explain the biogenesis of all tens of thousands of discovered circRNAs. Under the hypothesis that human circRNAs can be categorized according to different biogenesis mechanisms, we designed a contextual regression model trained to predict the formation of circular RNA from a random genomic locus on human genome, with potential biogenesis factors of circular RNA as the features of the training data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After achieving high prediction accuracy, we found through the feature extraction technique that the examined human circRNAs can be categorized into seven subgroups, according to the presence of the following sequence features: RNA editing sites, simple repeat sequences, self-chains, RNA binding protein binding sites and CpG islands within the flanking regions of the circular RNA back-spliced junction sites. These results support all of the previously reported biogenesis mechanisms of circRNA and solidify the idea that multiple biogenesis mechanisms co-exist for different subset of human circRNAs. Furthermore, we uncover a potential new links between circRNA biogenesis and flanking CpG island. We have also identified RNA binding proteins putatively correlated with circRNA biogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Scripts and tutorial are available at http:\/\/wanglab.ucsd.edu\/star\/circRNA. This program is under GNU General Public License v3.0.<\/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\/btz705","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T19:33:22Z","timestamp":1568316802000},"page":"4867-4870","source":"Crossref","is-referenced-by-count":12,"title":["Biogenesis mechanisms of circular RNA can be categorized through feature extraction of a machine learning model"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-729X","authenticated-orcid":false,"given":"Chengyu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Engineering in Medicine, University of California , San Diego, La Jolla, CA, USA"},{"name":"Institute of Bioinformatics and Systems Biology, National Chiao Tung University , HsinChu, Taiwan"},{"name":"Institute of Pharmacology, National Yang-Ming University , Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsien-Da","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences"},{"name":"Warshel Institute for Computational Biology, The Chinese University of Hong Kong , Shenzhen, Longgang District, Shenzhen, Guangdong Province, China"},{"name":"Shenzhen Bay Laboratory , Nanshan District, Shenzhen, Guangdong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"2023013108304884700_btz705-B1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1182\/blood-2015-06-649434","article-title":"Circular RNA enrichment in platelets is a signature of transcriptome degradation","volume":"127","author":"Alhasan","year":"2016","journal-title":"Blood"},{"key":"2023013108304884700_btz705-B2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"circRNA biogenesis competes with pre-mRNA splicing","volume":"56","author":"Ashwal-Fluss","year":"2014","journal-title":"Mol. 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