Methodology article

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

author email corresponding author email

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

Published:	21 February 2006

Abstract

Background

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.