{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T18:43:58Z","timestamp":1747248238734},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Next-generation RNA sequencing (RNA-seq) has been widely used to investigate alternative isoform regulations. Among them, alternative 3\u2032 splice site (SS) and 5\u2032 SS account for more than 30% of all alternative splicing (AS) events in higher eukaryotes. Recent studies have revealed that they play important roles in building complex organisms and have a critical impact on biological functions which could cause disease. Quite a few analytical methods have been developed to facilitate alternative 3\u2032 SS and 5\u2032 SS studies using RNA-seq data. However, these methods have various limitations and their performances may be further improved.<\/jats:p><jats:p>Results: We propose an empirical Bayes change-point model to identify alternative 3\u2032 SS and 5\u2032 SS. Compared with previous methods, our approach has several unique merits. First of all, our model does not rely on annotation information. Instead, it provides for the first time a systematic framework to integrate various information when available, in particular the useful junction read information, in order to obtain better performance. Second, we utilize an empirical Bayes model to efficiently pool information across genes to improve detection efficiency. Third, we provide a flexible testing framework in which the user can choose to address different levels of questions, namely, whether alternative 3\u2032 SS or 5\u2032 SS happens, and\/or where it happens. Simulation studies and real data application have demonstrated that our method is powerful and accurate.<\/jats:p><jats:p>Availability and implementation: The software is implemented in Java and can be freely downloaded from http:\/\/ebchangepoint.sourceforge.net\/.<\/jats:p><jats:p>Contact: \u00a0zhiwei@njit.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw060","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T01:09:07Z","timestamp":1455498547000},"page":"1823-1831","source":"Crossref","is-referenced-by-count":13,"title":["An empirical Bayes change-point model for identifying 3\u2032 and 5\u2032 alternative splicing by next-generation RNA sequencing"],"prefix":"10.1093","volume":"32","author":[{"given":"Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,2,11]]},"reference":[{"key":"2023020112295889300_btw060-B1","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1101\/gr.133744.111","article-title":"Detecting differential usage of exons from RNA-seq data","volume":"22","author":"Anders","year":"2012","journal-title":"Genome Res"},{"key":"2023020112295889300_btw060-B2","first-page":"260","article-title":"Product partition models for change point problems","author":"Barry","year":"1992","journal-title":"Ann. Stat"},{"key":"2023020112295889300_btw060-B3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/01621459.1993.10594323","article-title":"A Bayesian analysis for change point problems","volume":"88","author":"Barry","year":"1993","journal-title":"J. Am. Stat. Assoc"},{"key":"2023020112295889300_btw060-B4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/pcmr.12194","article-title":"Notch signaling in melanoma: interacting pathways and stromal influences that enhance notch targeting","volume":"27","author":"Bedogni","year":"2014","journal-title":"Pigm. Cell Melanoma Res"},{"key":"2023020112295889300_btw060-B5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"2023020112295889300_btw060-B6","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":"2023020112295889300_btw060-B7","doi-asserted-by":"crossref","first-page":"W348","DOI":"10.1093\/nar\/gkq448","article-title":"rquant. web: a tool for rna-seq-based transcript quantitation","volume":"38","author":"Bohnert","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023020112295889300_btw060-B8","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1137\/0916069","article-title":"A limited memory algorithm for bound constrained optimization","volume":"16","author":"Byrd","year":"1995","journal-title":"SIAM J. Sci. Comput"},{"key":"2023020112295889300_btw060-B9","volume-title":"Bayesian Methods for Nonlinear Classification and Regression","author":"Denison","year":"2002"},{"key":"2023020112295889300_btw060-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1198\/016214505000000033","article-title":"Bayesians, frequentists, and scientists","volume":"100","author":"Efron","year":"2005","journal-title":"J. Am. Stat. Assoc"},{"key":"2023020112295889300_btw060-B11","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511761362","volume-title":"Large-Scale Inference: Empirical Bayes Methods for Estimation, Testing, and Prediction","author":"Efron","year":"2010"},{"key":"2023020112295889300_btw060-B12","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/nmeth.2722","article-title":"Systematic evaluation of spliced alignment programs for RNA-seq data","volume":"10","author":"Engstr\u00f6m","year":"2013","journal-title":"Nat. Methods"},{"key":"2023020112295889300_btw060-B13","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1101\/gr.140061.112","article-title":"BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration","volume":"22","author":"Flockhart","year":"2012","journal-title":"Genome Res"},{"key":"2023020112295889300_btw060-B14","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nmeth.1503","article-title":"Alternative expression analysis by RNA sequencing","volume":"7","author":"Griffith","year":"2010","journal-title":"Nat. Methods"},{"key":"2023020112295889300_btw060-B15","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.tig.2011.02.004","article-title":"Genetic therapies for RNA mis-splicing diseases","volume":"27","author":"Hammond","year":"2011","journal-title":"Trends Genet"},{"key":"2023020112295889300_btw060-B16","doi-asserted-by":"crossref","first-page":"e39\u2013e39","DOI":"10.1093\/nar\/gks1026","article-title":"Diffsplice: the genome-wide detection of differential splicing events with RNA-seq","volume":"41","author":"Hu","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023020112295889300_btw060-B17","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/cmb.2012.0230","article-title":"A robust method for transcript quantification with RNA-seq data","volume":"20","author":"Huang","year":"2013","journal-title":"J. Comput. Biol"},{"key":"2023020112295889300_btw060-B18","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrg3052","article-title":"Functional consequences of developmentally regulated alternative splicing","volume":"12","author":"Kalsotra","year":"2011","journal-title":"Nat. Rev. Genet"},{"key":"2023020112295889300_btw060-B19","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nmeth.1528","article-title":"Analysis and design of RNA sequencing experiments for identifying isoform regulation","volume":"7","author":"Katz","year":"2010","journal-title":"Nat. Methods"},{"key":"2023020112295889300_btw060-B20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrg2776","article-title":"Alternative splicing and evolution: diversification, exon definition and function","volume":"11","author":"Keren","year":"2010","journal-title":"Nat. Rev. Genet"},{"key":"2023020112295889300_btw060-B21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"Rsem: accurate transcript quantification from RNA-seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf"},{"key":"2023020112295889300_btw060-B22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/bioinformatics\/btp692","article-title":"RNA-seq gene expression estimation with read mapping uncertainty","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020112295889300_btw060-B23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and quantifying mammalian transcriptomes by RNA-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"2023020112295889300_btw060-B24","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat. Genet"},{"key":"2023020112295889300_btw060-B25","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/onc.2010.418","article-title":"Critical role of endoglin in tumor cell plasticity of ewing sarcoma and melanoma","volume":"30","author":"Pardali","year":"2011","journal-title":"Oncogene"},{"key":"2023020112295889300_btw060-B26","doi-asserted-by":"crossref","first-page":"R22","DOI":"10.1186\/gb-2011-12-3-r22","article-title":"Improving rna-seq expression estimates by correcting for fragment bias","volume":"12","author":"Roberts","year":"2011","journal-title":"Genome Biol"},{"key":"2023020112295889300_btw060-B27","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/nbt.2957","article-title":"A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the sequencing quality control consortium","volume":"32","author":"SEQC\/MAQC-III Consortium","year":"2014","journal-title":"Nat. Biotechnol"},{"key":"2023020112295889300_btw060-B28","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/nar\/gkr1291","article-title":"MATS: a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data","volume":"40","author":"Shen","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023020112295889300_btw060-B29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrg3642","article-title":"Sequencing depth and coverage: key considerations in genomic analyses","volume":"15","author":"Sims","year":"2014","journal-title":"Nat. Rev. Genet"},{"key":"2023020112295889300_btw060-B30","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1093\/bioinformatics\/btr458","article-title":"Fdm: a graph-based statistical method to detect differential transcription using RNA-seq data","volume":"27","author":"Singh","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020112295889300_btw060-B31","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.molmed.2012.06.006","article-title":"Pre-mRNA splicing in disease and therapeutics","volume":"18","author":"Singh","year":"2012","journal-title":"Trends Mol. Med"},{"key":"2023020112295889300_btw060-B32","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/biomet\/asv012","article-title":"Hierarchical recognition of sparse patterns in large-scale simultaneous inference","volume":"102","author":"Sun","year":"2015","journal-title":"Biometrika"},{"key":"2023020112295889300_btw060-B33","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":"2023020112295889300_btw060-B34","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol"},{"key":"2023020112295889300_btw060-B35","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1186\/gb-2011-12-2-r13","article-title":"Haplotype and isoform specific expression estimation using multi-mapping rna-seq reads","volume":"12","author":"Turro","year":"2011","journal-title":"Genome Biol"},{"key":"2023020112295889300_btw060-B36","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"2023020112295889300_btw060-B37","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1093\/bioinformatics\/btu189","article-title":"A change-point model for identifying 3\u2019UTR switching by next-generation RNA sequencing","volume":"30","author":"Wang","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020112295889300_btw060-B38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"Rna-seq: a revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet"},{"key":"2023020112295889300_btw060-B39","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1093\/bioinformatics\/btr508","article-title":"Splicetrap: a method to quantify alternative splicing under single cellular conditions","volume":"27","author":"Wu","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020112295889300_btw060-B40","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/bioinformatics\/btq696","article-title":"Using non-uniform read distribution models to improve isoform expression inference in RNA-seq","volume":"27","author":"Wu","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020112295889300_btw060-B41","author":"Xuan","year":"2007"},{"key":"2023020112295889300_btw060-B42","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.bbamcr.2006.07.001","article-title":"Regulation of the actin cytoskeleton in cancer cell migration and invasion","volume":"1773","author":"Yamaguchi","year":"2007","journal-title":"Biochimica Et Biophysica Acta (BBA)-Molecular Cell Res"},{"key":"2023020112295889300_btw060-B43","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1214\/13-AOAS660","article-title":"An empirical Bayes testing procedure for detecting variants in analysis of next generation sequencing data","volume":"7","author":"Zhao","year":"2013","journal-title":"Ann. Appl. Stat"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/12\/1823\/49022833\/bioinformatics_32_12_1823.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/12\/1823\/49022833\/bioinformatics_32_12_1823.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T10:40:44Z","timestamp":1718361644000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/12\/1823\/1743857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,11]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btw060","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,6,15]]},"published":{"date-parts":[[2016,2,11]]}}}