title: A change-point model for identifying 3'UTR switching by next-generation RNA sequencing.
abstract: BACKGROUND
  Next-generation RNA sequencing offers an opportunity to investigate transcriptome in an unprecedented scale. Recent studies have revealed widespread alternative polyadenylation (polyA) in eukaryotes, leading to various mRNA isoforms differing in their 3' untranslated regions (3'UTR), through which, the stability, localization and translation of mRNA can be regulated. However, very few, if any, methods and tools are available for directly analyzing this special alternative RNA processing event. Conventional methods rely on annotation of polyA sites; yet, such knowledge remains incomplete, and identification of polyA sites is still challenging. The goal of this article is to develop methods for detecting 3'UTR switching without any prior knowledge of polyA annotations.
  
  
  RESULTS
  We propose a change-point model based on a likelihood ratio test for detecting 3'UTR switching. We develop a directional testing procedure for identifying dramatic shortening or lengthening events in 3'UTR, while controlling mixed directional false discovery rate at a nominal level. To our knowledge, this is the first approach to analyze 3'UTR switching directly without relying on any polyA annotations. Simulation studies and applications to two real datasets reveal that our proposed method is powerful, accurate and feasible for the analysis of next-generation RNA sequencing data.
  
  
  CONCLUSIONS
  The proposed method will fill a void among alternative RNA processing analysis tools for transcriptome studies. It can help to obtain additional insights from RNA sequencing data by understanding gene regulation mechanisms through the analysis of 3'UTR switching.
  
  
  METHODS
  The software is implemented in Java and can be freely downloaded from http://utr.sourceforge.net/.
  
  
  BACKGROUND
  zhiwei@njit.edu or hongzhe@mail.med.upenn.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102 and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102 and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102 and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D026723:Polyadenylation; D059368:RNA Isoforms / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D059368:RNA Isoforms
references.citation: J Proteome Res. 2012 Dec 7;11(12):6080-101
references.pmid: 23051583
references.citation: Nat Struct Mol Biol. 2012 Aug;19(8):845-52
references.pmid: 22820990
references.citation: Cell Rep. 2012 Mar 29;1(3):277-89
references.pmid: 22685694
references.citation: Nature. 2008 Nov 27;456(7221):470-6
references.pmid: 18978772
references.citation: Genome Biol. 2012 Jan 31;13(1):R4
references.pmid: 22293517
references.citation: Neuron. 2008 Dec 26;60(6):1022-38
references.pmid: 19109909
references.citation: Science. 2008 Jun 20;320(5883):1643-7
references.pmid: 18566288
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D116-20
references.pmid: 15608159
references.citation: J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
references.pmid: 16478745
references.citation: Nucleic Acids Res. 2012 Sep 1;40(17):8460-71
references.pmid: 22753024
references.citation: Mol Syst Biol. 2011 Sep 27;7:534
references.pmid: 21952137
references.citation: Genes Dev. 2011 Sep 1;25(17):1770-82
references.pmid: 21896654
references.citation: Genome Res. 2012 Oct;22(10):2054-66
references.pmid: 22722342
references.citation: Nat Biotechnol. 2013 Jan;31(1):46-53
references.pmid: 23222703
references.citation: Mol Cell Probes. 2010 Apr;24(2):87-92
references.pmid: 19837153
references.citation: Nucleic Acids Res. 2011 Mar;39(6):2393-403
references.pmid: 21075793
references.citation: Science. 2005 Sep 2;309(5740):1514-8
references.pmid: 16141059
references.citation: Cell. 2009 Feb 20;136(4):719-30
references.pmid: 19239891
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19348-53
references.pmid: 24191055
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7028-33
references.pmid: 19372383
references.citation: Genes Dev. 1997 Nov 1;11(21):2755-66
references.pmid: 9353246
references.citation: Nat Methods. 2010 Dec;7(12):1009-15
references.pmid: 21057496
references.citation: Genes Dev. 2013 Apr 1;27(7):734-48
references.pmid: 23530127
references.citation: PLoS One. 2012;7(2):e31129
references.pmid: 22347440
references.citation: Biometrics. 2010 Jun;66(2):485-92
references.pmid: 19645703
references.citation: Nucleic Acids Res. 2012 Apr;40(8):e61
references.pmid: 22266656
references.citation: Nat Rev Genet. 2010 Jan;11(1):75-87
references.pmid: 20019688
references.citation: Nat Rev Genet. 2010 May;11(5):345-55
references.pmid: 20376054
references.citation: Nat Methods. 2010 Oct;7(10):843-7
references.pmid: 20835245
references.citation: Nat Genet. 2006 Jun;38(6):626-35
references.pmid: 16645617
references.citation: Nat Rev Genet. 2009 Jan;10(1):57-63
references.pmid: 19015660
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Nature. 2010 Dec 2;468(7324):664-8
references.pmid: 20881964
references.citation: Nat Methods. 2012 Mar 04;9(4):357-9
references.pmid: 22388286
references.citation: Nucleic Acids Res. 2005 Jan 12;33(1):201-12
references.pmid: 15647503
references.citation: Genome Res. 2011 May;21(5):741-7
references.pmid: 21474764
references.citation: Genes Dev. 2010 Nov 1;24(21):2343-64
references.pmid: 21041405
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Carcinogenesis. 2009 Mar;30(3):397-407
references.pmid: 19126645
references.citation: Cancer Res. 2013 Apr 1;73(7):2247-58
references.pmid: 23358685
references.citation: Genome Res. 2012 Oct;22(10):2008-17
references.pmid: 22722343
references.citation: Cell. 2009 Aug 21;138(4):673-84
references.pmid: 19703394
references.citation: Cell. 2012 Jul 6;150(1):53-64
references.pmid: 22770214
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D165-8
references.pmid: 17202160
references.citation: Breast Cancer Res Treat. 2012 Feb;131(3):791-800
references.pmid: 21452021