%0 Journal Article
%T CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays
%A Jing Huang
%A Wen Wei
%A Joyce Chen
%A Jane Zhang
%A Guoying Liu
%A Xiaojun Di
%A Rui Mei
%A Shumpei Ishikawa
%A Hiroyuki Aburatani
%A Keith W Jones
%A Michael H Shapero
%J BMC Bioinformatics
%D 2006
%I BioMed Central
%R 10.1186/1471-2105-7-83
%X 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.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.The cancer cell karyotype is often complex and can include a range of molecular alterations that span mutations at the single nucleotide level to extensive rearrangements involving whole chromosomes. The activation of oncogenes as the result of DNA amplifications and the inactivation of tumor suppressor genes as the result of DNA deletions can both contribute to the cancer cell phenotype. With the recent identification of large scale copy number polymorphisms (CNPs) in the human genome as well, it is increasingly clear that a detailed understanding of the role of genomic alterations and structure will be important in the context of both the normal and disease state [1-8]. Over the years many experimental approaches have been described that have increased our knowledge of the cancer genome. These include genome-wide approaches such as array comparative genomic hybridization (array
%U http://www.biomedcentral.com/1471-2105/7/83