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PMID: 16504045 Published · epublish English Journal Article

CARAT: a novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays.

BMC bioinformatics ·Vol. 7 ·2006-02-21 ·Pages 83

Huang J, Wei W, Chen J, Zhang J, Liu G, Di X, Mei R, Ishikawa S, Aburatani H, Jones KW, Shapero MH

Abstract

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. 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.

MeSH Terms
Algorithms Alleles Chromosome Mapping/methods Chromosomes, Human, X/genetics DNA Mutational Analysis/methods DNA, Neoplasm/genetics Gene Dosage/genetics Gene Frequency/genetics Humans Oligonucleotide Array Sequence Analysis/methods Polymorphism, Single Nucleotide/genetics Reproducibility of Results Sensitivity and Specificity Sequence Analysis, DNA/methods
Chemicals
DNA, Neoplasm
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Huang Jing
Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA 95051, USA. jing_huang@affymetrix.com
Wei Wen
Chen Joyce
Zhang Jane
Liu Guoying
Di Xiaojun
Mei Rui
Ishikawa Shumpei
Aburatani Hiroyuki
Jones Keith W
Shapero Michael H
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Article Info
Journal
BMC bioinformatics
Abbr.
BMC Bioinformatics
ISSN
1471-2105
DOI
10.1186/1471-2105-7-83
Email
jing_huang@affymetrix.com
Published
2006-02-21
Epub
2006-00-21
Pages
83
Language
English
Region
England
NLM ID
100965194
PMCID
PMC1402331
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2105-7-83 PMC Full Text View journal details
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