Reference-unbiased copy number variant analysis using CGH microarrays.
Comparative genomic hybridization (CGH) microarrays have been used to determine copy number variations (CNVs) and their effects on complex diseases. Detection of absolute CNVs independent of genomic variants of an arbitrary reference sample has been a critical issue in CGH array experiments. Whole genome analysis using massively parallel sequencing with multiple ultra-high resolution CGH arrays provides an opportunity to catalog highly accurate genomic variants of the reference DNA (NA10851). Using information on variants, we developed a new method, the CGH array reference-free algorithm (CARA), which can determine reference-unbiased absolute CNVs from any CGH array platform. The algorithm enables the removal and rescue of false positive and false negative CNVs, respectively, which appear due to the effects of genomic variants of the reference sample in raw CGH array experiments. We found that the CARA remarkably enhanced the accuracy of CGH array in determining absolute CNVs. Our method thus provides a new approach to interpret CGH array data for personalized medicine.
Ju
Young Seok
YS
Genomic Medicine Institute, Medical Research Center, Seoul National University, Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Hong
Dongwan
D
Kim
Sheehyun
S
Park
Sung-Soo
SS
Kim
Sujung
S
Lee
Seungbok
S
Park
Hansoo
H
Kim
Jong-Il
JI
Seo
Jeong-Sun
JS
D000465:Algorithms; D055028:Comparative Genomic Hybridization / Q000379:methods* / Q000592:standards; D056915:DNA Copy Number Variations; D015894:Genome, Human; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012015:Reference Standards; D012984:Software
Nat Genet. 2005 Jul;37(7):727-32
15895083
Annu Rev Genomics Hum Genet. 2009;10:451-81
19715442
Nat Genet. 2010 May;42(5):400-5
20364138
Nat Genet. 2007 Jul;39(7 Suppl):S7-15
17597783
Science. 2004 Jul 23;305(5683):525-8
15273396
Nature. 2008 May 1;453(7191):56-64
18451855
Nature. 2008 Nov 6;456(7218):60-5
18987735
Bioinformatics. 2010 Apr 1;26(7):873-81
20147302
Nature. 2008 Nov 6;456(7218):53-9
18987734
Am J Hum Genet. 2008 Mar;82(3):685-95
18304495
Nat Genet. 2004 Sep;36(9):949-51
15286789
Genome Res. 2008 Nov;18(11):1698-710
18775914
Nat Genet. 2009 Oct;41(10):1061-7
19718026
Nature. 2008 Apr 17;452(7189):872-6
18421352
Nat Methods. 2009 Jan;6(1):99-103
19043412
Nature. 2010 Apr 1;464(7289):704-12
19812545
Genome Res. 2003 Oct;13(10):2291-305
12975311
Genome Res. 2009 Sep;19(9):1586-92
19657104
Nat Genet. 2007 Jul;39(7 Suppl):S16-21
17597776
Nature. 2009 Aug 20;460(7258):1011-5
19587683
Nature. 2001 Feb 15;409(6822):860-921
11237011
Science. 2007 Oct 19;318(5849):420-6
17901297
Nature. 2006 Nov 23;444(7118):444-54
17122850
Trends Genet. 2008 May;24(5):238-45
18378036