title: CARAT: a novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA 95051, USA. jing_huang@affymetrix.com
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Wen
authors.initials: W
authors.lastname: Wei
authors.forename: Joyce
authors.initials: J
authors.lastname: Chen
authors.forename: Jane
authors.initials: J
authors.lastname: Zhang
authors.forename: Guoying
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Di
authors.forename: Rui
authors.initials: R
authors.lastname: Mei
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Keith W
authors.initials: KW
authors.lastname: Jones
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shapero
mesh_terms: D000465:Algorithms; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm