title: MATCHCLIP: locate precise breakpoints for copy number variation using CIGAR string by matching soft clipped reads.
abstract: Copy number variations (CNVs) are associated with many complex diseases. Next generation sequencing data enable one to identify precise CNV breakpoints to better under the underlying molecular mechanisms and to design more efficient assays. Using the CIGAR strings of the reads, we develop a method that can identify the exact CNV breakpoints, and in cases when the breakpoints are in a repeated region, the method reports a range where the breakpoints can slide. Our method identifies the breakpoints of a CNV using both the positions and CIGAR strings of the reads that cover breakpoints of a CNV. A read with a long soft clipped part (denoted as S in CIGAR) at its 3'(right) end can be used to identify the 5'(left)-side of the breakpoints, and a read with a long S part at the 5' end can be used to identify the breakpoint at the 3'-side. To ensure both types of reads cover the same CNV, we require the overlapped common string to include both of the soft clipped parts. When a CNV starts and ends in the same repeated regions, its breakpoints are not unique, in which case our method reports the left most positions for the breakpoints and a range within which the breakpoints can be incremented without changing the variant sequence. We have implemented the methods in a C++ package intended for the current Illumina Miseq and Hiseq platforms for both whole genome and exon-sequencing. Our simulation studies have shown that our method compares favorably with other similar methods in terms of true discovery rate, false positive rate and breakpoint accuracy. Our results from a real application have shown that the detected CNVs are consistent with zygosity and read depth information. The software package is available at http://statgene.med.upenn.edu/softprog.html.
authors: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine Philadelphia, PA, USA.
authors: Yinghua
authors: Y
authors: Wu
authors: Lifeng
authors: L
authors: Tian
authors: Mario
authors: M
authors: Pirastu
authors: Dwight
authors: D
authors: Stambolian
authors: Hongzhe
authors: H
authors: Li
keywords: breakpoint; deletion; duplication; exon sequencing; structural variation
references: Bioinformatics. 2009 Jul 15;25(14):1754-60
references: 19451168
references: Nat Methods. 2009 Sep;6(9):677-81
references: 19668202
references: Nature. 2010 Oct 28;467(7319):1061-73
references: 20981092
references: Bioinformatics. 2010 Mar 1;26(5):589-95
references: 20080505
references: Brief Bioinform. 2010 Sep;11(5):473-83
references: 20460430
references: Bioinformatics. 2012 Oct 15;28(20):2576-83
references: 22851530
references: Genome Res. 2009 Sep;19(9):1586-92
references: 19657104
references: Nat Genet. 2007 Jul;39(7 Suppl):S16-21
references: 17597776
references: Nucleic Acids Res. 2012 Oct;40(18):e145
references: 22735696
references: Genome Res. 2002 Apr;12(4):656-64
references: 11932250
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D968-74
references: 20972221
references: Nat Rev Genet. 2011 May;12(5):363-76
references: 21358748
references: Bioinformatics. 2009 Jun 15;25(12):i222-30
references: 19477992
references: Genome Res. 2006 Aug;16(8):949-61
references: 16809666
references: Bioinformatics. 2012 Sep 15;28(18):i333-i339
references: 22962449
references: Nat Methods. 2011 Jun 12;8(8):652-4
references: 21666668
references: Nature. 2010 Apr 1;464(7289):704-12
references: 19812545
references: Genome Res. 2010 Sep;20(9):1297-303
references: 20644199
references: Nat Genet. 2011 Mar;43(3):269-76
references: 21317889
references: Nat Genet. 2011 May;43(5):491-8
references: 21478889
references: Bioinformatics. 2012 Jul 15;28(14):1838-44
references: 22569178
references: Curr Protoc Hum Genet. 2012 Oct;Chapter 7:Unit7.19
references: 23074071
references: Nat Methods. 2012 Mar 04;9(4):357-9
references: 22388286
references: Bioinformatics. 2009 Nov 1;25(21):2865-71
references: 19561018
references: Nature. 2011 Feb 3;470(7332):59-65
references: 21293372
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D832-6
references: 19015121
references: PLoS One. 2011 Jan 31;6(1):e16327
references: 21305028
references: Bioinformatics. 2012 Nov 1;28(21):2711-8
references: 22942022
references: Genome Res. 2011 Jun;21(6):974-84
references: 21324876
references: Genome Res. 1999 Sep;9(9):868-77
references: 10508846
references: Genome Res. 2010 Nov;20(11):1613-22
references: 20805290
references: Bioinformatics. 2009 Aug 15;25(16):2078-9
references: 19505943
references: Nature. 2011 Feb 10;470(7333):198-203
references: 21307932
references: Nat Rev Genet. 2009 Aug;10(8):551-64
references: 19597530