{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T05:08:28Z","timestamp":1740287308647,"version":"3.37.3"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: The RNA-seq paired-end read (PER) protocol samples transcript fragments longer than the sequencing capability of today's technology by sequencing just the two ends of each fragment. Deep sampling of the transcriptome using the PER protocol presents the opportunity to reconstruct the unsequenced portion of each transcript fragment using end reads from overlapping PERs, guided by the expected length of the fragment.<\/jats:p><jats:p>Methods: A probabilistic framework is described to predict the alignment to the genome of all PER transcript fragments in a PER dataset. Starting from possible exonic and spliced alignments of all end reads, our method constructs potential splicing paths connecting paired ends. An expectation maximization method assigns likelihood values to all splice junctions and assigns the most probable alignment for each transcript fragment.<\/jats:p><jats:p>Results: The method was applied to 2 \u00d7 35 bp PER datasets from cancer cell lines MCF-7 and SUM-102. PER fragment alignment increased the coverage 3-fold compared to the alignment of the end reads alone, and increased the accuracy of splice detection. The accuracy of the expectation maximization (EM) algorithm in the presence of alternative paths in the splice graph was validated by qRT\u2013PCR experiments on eight exon skipping alternative splicing events. PER fragment alignment with long-range splicing confirmed 8 out of 10 fusion events identified in the MCF-7 cell line in an earlier study by (Maher et al., 2009).<\/jats:p><jats:p>Availability: Software available at http:\/\/www.netlab.uky.edu\/p\/bioinfo\/MapSplice\/PER<\/jats:p><jats:p>Contact: \u00a0liuj@cs.uky.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq336","type":"journal-article","created":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T00:19:35Z","timestamp":1277425175000},"page":"1950-1957","source":"Crossref","is-referenced-by-count":19,"title":["A probabilistic framework for aligning paired-end RNA-seq data"],"prefix":"10.1093","volume":"26","author":[{"given":"Yin","family":"Hu","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]},{"given":"Xiaping","family":"He","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]},{"given":"Derek Y.","family":"Chiang","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]},{"given":"Jan F.","family":"Prins","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]},{"given":"Jinze","family":"Liu","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Kentucky, Lexington, KY, 2Department of Genetics and 3Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,6,23]]},"reference":[{"key":"2023012508030508000_B1","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkq211","article-title":"Detection of splice junctions from paired-end RNA-seq data by splicemap","author":"Au","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023012508030508000_B2","doi-asserted-by":"crossref","DOI":"10.1101\/gr.103697.109","article-title":"Integrative analysis of the melanoma transcriptome","author":"Berger","year":"2010","journal-title":"Genome Res."},{"key":"2023012508030508000_B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","article-title":"Maximum likelihood from incomplete data via the EM algorithm","volume":"39","author":"Dempster","year":"1977","journal-title":"J. R. Stat. Soc."},{"key":"2023012508030508000_B4","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1101\/gr.092759.109","article-title":"Circos: an information aesthetic for comparative genomics","volume":"19","author":"Krzywinski","year":"2009","journal-title":"Genome Res."},{"key":"2023012508030508000_B5","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1101\/gr.078212.108","article-title":"Mapping short DNA sequencing reads and calling variants using mapping quality scores","volume":"18","author":"Li","year":"2008","journal-title":"Genome Res."},{"key":"2023012508030508000_B6","doi-asserted-by":"crossref","first-page":"12353","DOI":"10.1073\/pnas.0904720106","article-title":"Chimeric transcript discovery by paired-end transcriptome sequencing","volume":"106","author":"Maher","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508030508000_B7","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012508030508000_B8","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkq622","article-title":"Accurate mapping of RNA-seq reads for splice junction discovery","author":"Wang","year":"2010","journal-title":"Nucleic Acid Res."},{"key":"2023012508030508000_B9","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1214\/aos\/1176346060","article-title":"On the convergence properties of the EM algorithm","volume":"11","author":"Wu","year":"1983","journal-title":"Ann. 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