{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:32:55Z","timestamp":1763641975649},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation : Photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) is an experimental method based on next-generation sequencing for identifying the RNA interaction sites of a given protein. The method deliberately inserts T-to-C substitutions at the RNA-protein interaction sites, which provides a second layer of evidence compared with other CLIP methods. However, the experiment includes several sources of noise which cause both low-frequency errors and spurious high-frequency alterations. Therefore, rigorous statistical analysis is required in order to separate true T-to-C base changes, following cross-linking, from noise. So far, most of the existing PAR-CLIP data analysis methods focus on discarding the low-frequency errors and rely on high-frequency substitutions to report binding sites, not taking into account the possibility of high-frequency false positive substitutions.<\/jats:p>\n               <jats:p>Results : Here, we introduce BMix , a new probabilistic method which explicitly accounts for the sources of noise in PAR-CLIP data and distinguishes cross-link induced T-to-C substitutions from low and high-frequency erroneous alterations. We demonstrate the superior speed and accuracy of our method compared with existing approaches on both simulated and real, publicly available human datasets.<\/jats:p>\n               <jats:p>Availability and implementation : The model is freely accessible within the BMix toolbox at www.cbg.bsse.ethz.ch\/software\/BMix , available for Matlab and R.<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data is available at Bioinformatics online.<\/jats:p>\n               <jats:p>Contact : niko.beerenwinkel@bsse.ethz.ch<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv520","type":"journal-article","created":{"date-parts":[[2015,9,6]],"date-time":"2015-09-06T00:18:10Z","timestamp":1441498690000},"page":"976-983","source":"Crossref","is-referenced-by-count":12,"title":["BMix: probabilistic modeling of occurring substitutions in PAR-CLIP data"],"prefix":"10.1093","volume":"32","author":[{"given":"Monica","family":"Golumbeanu","sequence":"first","affiliation":[{"name":"1 Department of Biosystems Science and Engineering and"},{"name":"2 SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland"}]},{"given":"Pejman","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering and"},{"name":"2 SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland"}]},{"given":"Niko","family":"Beerenwinkel","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering and"},{"name":"2 SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland"}]}],"member":"286","published-online":{"date-parts":[[2015,9,5]]},"reference":[{"key":"2023020112010165600_btv520-B1","first-page":"28","article-title":"Fitting a mixture model by expectation maximization to discover motifs in biopolymers","author":"Bailey","year":"1994"},{"key":"2023020112010165600_btv520-B2","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1101\/gad.1788009","article-title":"Current-generation high-throughput sequencing: deepening insights into mammalian transcriptomes","volume":"23","author":"Blencowe","year":"2009","journal-title":"Genes Dev."},{"key":"2023020112010165600_btv520-B3","doi-asserted-by":"crossref","first-page":"R18","DOI":"10.1186\/gb-2014-15-1-r18","article-title":"PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis","volume":"15","author":"Chen","year":"2014","journal-title":"Genome Biol."},{"key":"2023020112010165600_btv520-B4","doi-asserted-by":"crossref","first-page":"32+","DOI":"10.1186\/s12859-015-0470-y","article-title":"Sensitive and highly resolved identification of RNA-protein interaction sites in PAR-CLIP data","volume":"16","author":"Comoglio","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"2023020112010165600_btv520-B5","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/gb-2011-12-8-r79","article-title":"PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence data","volume":"12","author":"Corcoran","year":"2011","journal-title":"Genome Biol."},{"key":"2023020112010165600_btv520-B6","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/gb-2013-14-7-r79","article-title":"PARma: identification of microRNA target sites in AGO-PAR-CLIP data","volume":"14","author":"Erhard","year":"2013","journal-title":"Genome Biol."},{"key":"2023020112010165600_btv520-B7","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/nsmb.2115","article-title":"Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs","volume":"18","author":"Garcia","year":"2011","journal-title":"Nat. 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