{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:02Z","timestamp":1772138042300,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T00:00:00Z","timestamp":1611964800000},"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"}]},{"name":"Graduate School of Quantitative Biosciences Munich"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Alternative splicing removes intronic sequences from pre-mRNAs in alternative ways to produce different forms (isoforms) of mature mRNA. The composition of expressed transcripts gives specific functionalities to cells in a particular condition or developmental stage. In addition, a large fraction of human disease mutations affect splicing and lead to aberrant mRNA and protein products. Current methods that interrogate the transcriptome based on RNA-seq either suffer from short-read length when trying to infer full-length transcripts, or are restricted to predefined units of alternative splicing that they quantify from local read evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Instead of attempting to quantify individual outcomes of the splicing process such as local splicing events or full-length transcripts, we propose to quantify alternative splicing using a simplified probabilistic model of the underlying splicing process. Our model is based on the usage of individual splice sites and can generate arbitrarily complex types of splicing patterns. In our implementation, McSplicer, we estimate the parameters of our model using all read data at once and we demonstrate in our experiments that this yields more accurate estimates compared to competing methods. Our model is able to describe multiple effects of splicing mutations using few, easy to interpret parameters, as we illustrate in an experiment on RNA-seq data from autism spectrum disorder patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>McSplicer source code is available at https:\/\/github.com\/canzarlab\/McSplicer and has been deposited in archived format at https:\/\/doi.org\/10.5281\/zenodo.4449881.<\/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\/btab050","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T16:02:11Z","timestamp":1611590531000},"page":"2004-2011","source":"Crossref","is-referenced-by-count":6,"title":["McSplicer: a probabilistic model for estimating splice site usage from RNA-seq data"],"prefix":"10.1093","volume":"37","author":[{"given":"Israa","family":"Alqassem","sequence":"first","affiliation":[{"name":"Gene Center, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Munich 81377, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yash","family":"Sonthalia","sequence":"additional","affiliation":[{"name":"Dept. of Computer Science, Purdue University, West lafayette 47907, IN, USA\"and additionally add\"Present Address: Google , Kirkland 98033, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Klitzke-Feser","sequence":"additional","affiliation":[{"name":"Gene Center, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Munich 81377, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1375-9310","authenticated-orcid":false,"given":"Heejung","family":"Shim","sequence":"additional","affiliation":[{"name":"Melbourne Integrative Genomics and School of Mathematics and Statistics, University of Melbourne , Parkville, Victoria 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-8010","authenticated-orcid":false,"given":"Stefan","family":"Canzar","sequence":"additional","affiliation":[{"name":"Gene Center, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen , Munich 81377, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,30]]},"reference":[{"key":"2023061310311975700_btab050-B1","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1261\/rna.051557.115","article-title":"Leveraging transcript quantification for fast computation of alternative splicing profiles","volume":"21","author":"Alamancos","year":"2015","journal-title":"RNA"},{"key":"2023061310311975700_btab050-B2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s13353-018-0444-7","article-title":"Splicing mutations in human genetic disorders: examples, detection, and confirmation","volume":"59","author":"Anna","year":"2018","journal-title":"J. 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