title: CNV-TV: a robust method to discover copy number variation from short sequencing reads.
abstract: BACKGROUND
  Copy number variation (CNV) is an important structural variation (SV) in human genome. Various studies have shown that CNVs are associated with complex diseases. Traditional CNV detection methods such as fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) suffer from low resolution. The next generation sequencing (NGS) technique promises a higher resolution detection of CNVs and several methods were recently proposed for realizing such a promise. However, the performances of these methods are not robust under some conditions, e.g., some of them may fail to detect CNVs of short sizes. There has been a strong demand for reliable detection of CNVs from high resolution NGS data.
  
  
  RESULTS
  A novel and robust method to detect CNV from short sequencing reads is proposed in this study. The detection of CNV is modeled as a change-point detection from the read depth (RD) signal derived from the NGS, which is fitted with a total variation (TV) penalized least squares model. The performance (e.g., sensitivity and specificity) of the proposed approach are evaluated by comparison with several recently published methods on both simulated and real data from the 1000 Genomes Project.
  
  
  CONCLUSIONS
  The experimental results showed that both the true positive rate and false positive rate of the proposed detection method do not change significantly for CNVs with different copy numbers and lengthes, when compared with several existing methods. Therefore, our proposed approach results in a more reliable detection of CNVs than the existing methods.
authors: Department of Biomedical Engineering, Tulane University, New Orleans, LA, USA.
authors: Junbo
authors: J
authors: Duan
authors: Ji-Gang
authors: JG
authors: Zhang
authors: Hong-Wen
authors: HW
authors: Deng
authors: Yu-Ping
authors: YP
authors: Wang
mesh_terms: D056915:DNA Copy Number Variations; D015894:Genome, Human; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*
references: Ann Stat. 2008 Aug 1;36(4):1509-1533
references: 19823597
references: Nat Methods. 2009 Jan;6(1):99-103
references: 19043412
references: Genes (Basel). 2010 Sep 14;1(2):294-307
references: 24710047
references: Genome Res. 2009 Sep;19(9):1586-92
references: 19657104
references: Bioinformatics. 2011 Jan 15;27(2):268-9
references: 21081509
references: PLoS Comput Biol. 2010 Nov 11;6(11):e1000988
references: 21085617
references: Bioinformatics. 2010 Dec 15;26(24):3051-8
references: 20966003
references: Bioinformatics. 2005 Oct 1;21(19):3763-70
references: 16081473
references: Nature. 2008 Sep 11;455(7210):232-6
references: 18668039
references: Bioinformatics. 2009 Aug 15;25(16):2078-9
references: 19505943
references: Science. 2007 Apr 20;316(5823):445-9
references: 17363630
references: Nature. 2006 Nov 23;444(7118):444-54
references: 17122850
references: Genome Res. 2006 Aug;16(8):949-61
references: 16809666
references: BMC Bioinformatics. 2010 Aug 18;11:432
references: 20718989
references: Annu Rev Med. 2010;61:437-55
references: 20059347
references: BMC Bioinformatics. 2009 Mar 06;10:80
references: 19267900
references: Nat Genet. 2008 Jun;40(6):722-9
references: 18438408
references: Behav Genet. 2004 Nov;34(6):593-610
references: 15520516
references: Genome Biol. 2009;10(3):R25
references: 19261174
references: Genome Res. 2009 Jul;19(7):1270-8
references: 19447966
references: Am J Hum Genet. 2012 Sep 7;91(3):408-21
references: 22939633
references: Bioinformatics. 2010 Feb 15;26(4):565-7
references: 20022973
references: Nat Methods. 2009 Nov;6(11 Suppl):S13-20
references: 19844226
references: Nucleic Acids Res. 2012 May;40(9):e69
references: 22302147
references: Bioinformatics. 2012 Jan 1;28(1):40-7
references: 22039209
references: Bioinformatics. 2011 Jun 1;27(11):1513-20
references: 21505028
references: Nature. 2008 Nov 6;456(7218):53-9
references: 18987734
references: Am J Hum Genet. 2008 Dec;83(6):663-74
references: 18992858
references: Nature. 2011 Feb 3;470(7332):59-65
references: 21293372
references: IEEE/ACM Trans Comput Biol Bioinform. 2009 Oct-Dec;6(4):529-41
references: 19875853
references: Nat Genet. 2006 Jan;38(1):24-6
references: 16369530
references: PLoS One. 2011 Jan 31;6(1):e16327
references: 21305028
references: Nat Genet. 2004 Sep;36(9):949-51
references: 15286789
references: Genome Res. 2011 Jun;21(6):974-84
references: 21324876
references: Genome Res. 2010 Nov;20(11):1613-22
references: 20805290
references: J R Stat Soc Series B Stat Methodol. 2012 Mar;74(2):245-266
references: 25506256
references: Science. 2007 Oct 19;318(5849):420-6
references: 17901297
references: Nat Genet. 2009 Oct;41(10):1061-7
references: 19718026
references: PLoS One. 2013;8(3):e59128
references: 23527109