title: A comparison of DNA copy number profiling platforms.
abstract: The accurate mapping of recurring DNA copy number aberrations (CNAs), a hallmark feature of the cancer genome, has facilitated the discovery of tumor suppressor genes and oncogenes. Microarray-based assays designed to detect these chromosomal copy number alterations on a genome-wide and high-resolution scale have emerged as a cornerstone technology in the genomic era. The diversity of commercially available platforms prompted a systematic comparison of five copy number profiling assays for their ability to detect 2-fold copy number gain and loss (4n or 1n, respectively) as well as focal high-amplitude CNAs. Here, using a collection of established human melanoma cell lines, we defined the reproducibility, absolute signals, signal to noise, and false-positive and false-negative rates for each of the five assays against ground truth defined by spectral karyotyping, in addition to comparing the concordance of CNA detection by two high-resolution Agilent and Affymetrix microarray platforms. Our analyses concluded that the Agilent's 60-mer oligonucleotide microarray with probe design optimized for genomic hybridization offers the highest sensitivity and specificity (area under receiver operator characteristic curve >0.99), whereas Affymetrix's single nucleotide polymorphism microarray seems to offer better detection of CNAs in gene-poor regions. Availability of these comparison results should guide study design decisions and facilitate further computational development.
authors.affiliation: Translational Medicine, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Cristina
authors.initials: C
authors.lastname: Nogueira
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.forename: Ilana
authors.initials: I
authors.lastname: Perna
authors.forename: Katherine
authors.initials: K
authors.lastname: Nathanson
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
mesh_terms: D045744:Cell Line, Tumor; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity