{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:46:16Z","timestamp":1774975576236,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1201,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Pre-mRNA cleavage and polyadenylation are essential steps for 3\u2032-end maturation and subsequent stability and degradation of mRNAs. This process is highly controlled by cis-regulatory elements surrounding the cleavage\/polyadenylation sites (polyA sites), which are frequently constrained by sequence content and position. More than 50% of human transcripts have multiple functional polyA sites, and the specific use of alternative polyA sites (APA) results in isoforms with variable 3\u2032-untranslated regions, thus potentially affecting gene regulation. Elucidating the regulatory mechanisms underlying differential polyA preferences in multiple cell types has been hindered both by the lack of suitable data on the precise location of cleavage sites, as well as of appropriate tests for determining APAs with significant differences across multiple libraries.<\/jats:p>\n               <jats:p>Results: We applied a tailored paired-end RNA-seq protocol to specifically probe the position of polyA sites in three human adult tissue types. We specified a linear-effects regression model to identify tissue-specific biases indicating regulated APA; the significance of differences between tissue types was assessed by an appropriately designed permutation test. This combination allowed to identify highly specific subsets of APA events in the individual tissue types. Predictive models successfully classified constitutive polyA sites from a biologically relevant background (auROC = 99.6%), as well as tissue-specific regulated sets from each other. We found that the main cis-regulatory elements described for polyadenylation are a strong, and highly informative, hallmark for constitutive sites only. Tissue-specific regulated sites were found to contain other regulatory motifs, with the canonical polyadenylation signal being nearly absent at brain-specific polyA sites. Together, our results contribute to the understanding of the diversity of post-transcriptional gene regulation.<\/jats:p>\n               <jats:p>Availability: Raw data are deposited on SRA, accession numbers: brain SRX208132, kidney SRX208087 and liver SRX208134. Processed datasets as well as model code are published on our website: http:\/\/www.genome.duke.edu\/labs\/ohler\/research\/UTR\/<\/jats:p>\n               <jats:p>Contact: uwe.ohler@duke.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt233","type":"journal-article","created":{"date-parts":[[2013,6,27]],"date-time":"2013-06-27T05:33:26Z","timestamp":1372311206000},"page":"i108-i116","source":"Crossref","is-referenced-by-count":27,"title":["Genome-wide identification and predictive modeling of tissue-specific alternative polyadenylation"],"prefix":"10.1093","volume":"29","author":[{"given":"Dina","family":"Hafez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayan","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Ohler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,6,19]]},"reference":[{"key":"2023062614330516600_btt233-B1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3233\/ISB-2009-0395","article-title":"Prediction of polyadenylation signals in human DNA sequences using nucleotide frequencies","volume":"9","author":"Ahmed","year":"2009","journal-title":"In Silico Biol."},{"key":"2023062614330516600_btt233-B2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1186\/1471-2164-11-646","article-title":"POLYAR, a new computer program for prediction of poly (A) sites in human sequences","volume":"11","author":"Akhtar","year":"2010","journal-title":"BMC Genomics"},{"key":"2023062614330516600_btt233-B3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.tcb.2009.06.001","article-title":"To localize or not to localize: mRNA fate is in 3\u2032UTR ends","volume":"19","author":"Andreassi","year":"2009","journal-title":"Trends Cell Biol."},{"key":"2023062614330516600_btt233-B4","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1101\/gr.190501","article-title":"Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data","volume":"11","author":"Beaudoing","year":"2001","journal-title":"Genome Res."},{"key":"2023062614330516600_btt233-B5","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1101\/gr.10.7.1001","article-title":"Patterns of variant polyadenylation signal usage in human genes","volume":"10","author":"Beaudoing","year":"2000","journal-title":"Genome Res."},{"key":"2023062614330516600_btt233-B6","doi-asserted-by":"crossref","first-page":"e1000173","DOI":"10.1371\/journal.pcbi.1000173","article-title":"Support vector machines and kernels for computational biology","volume":"4","author":"Ben-Hur","year":"2008","journal-title":"PLoS Comput. 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