CNVs and SNPs Methods paper

CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays
Jing Huang1 , Wen Wei1 , Joyce Chen1 , Jane Zhang1 , Guoying Liu1 , Xiaojun Di1 , Rui Mei1 , Shumpei Ishikawa2 , Hiroyuki Aburatani2 , Keith W Jones1 and Michael H Shapero1
1Affymetrix, Inc. 3420 Central Expressway, Santa Clara CA 95051, USA
2University of Tokyo, Genome Science Division Research Center for Advanced Science and Technology, 4-6-1 Komaba, Meguro, 153-8904, Tokyo

BMC Bioinformatics 2006, 7:83 doi:10.1186/1471-2105-7-83

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2105/7/83

Received 2 July 2005
Accepted 21 February 2006
Published 21 February 2006

© 2006 Huang et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
--------------------------------------------------------------------------------



DNA copy number alterations are one of the main characteristics of the cancer cell karyotype and can contribute to the complex phenotype of these cells. These alterations can lead to gains in cellular oncogenes as well as losses in tumor suppressor genes and can span small intervals as well as involve entire chromosomes. The ability to accurately detect these changes is central to understanding how they impact the biology of the cell.

Results

We describe a novel algorithm called CARAT (Copy Number Analysis with Regression And Tree) that uses probe intensity information to infer copy number in an allele-specific manner from high density DNA oligonuceotide arrays designed to genotype over 100, 000 SNPs. Total and allele-specific copy number estimations using CARAT are independently evaluated for a subset of SNPs using quantitative PCR and allelic TaqMan reactions with several human breast cancer cell lines. The sensitivity and specificity of the algorithm are characterized using DNA samples containing differing numbers of X chromosomes as well as a test set of normal individuals. Results from the algorithm show a high degree of agreement with results from independent verification methods.

Conclusion

Overall, CARAT automatically detects regions with copy number variations and assigns a significance score to each alteration as well as generating allele-specific output. When coupled with SNP genotype calls from the same array, CARAT provides additional detail into the structure of genome wide alterations that can contribute to allelic imbalance