A Systematic Comparison of Microarray Platforms for DNA Copy Number Profiling
A Systematic Comparison of Microarray Platforms for DNA Copy Number Profiling
A review of A Comparison of DNA Copy Number Profiling Platforms
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Genomic copy number aberrations (CNAs) frequently occur in cancers and microarray-based comparative genomic hybridization (CGH) is a key technology for copy number profiling. Considering the diversity of microarray platforms available, Greshock and colleagues at multiple institutes (2007) compared microarray-based CGH assays with the goal of providing information that is important for experiment design decisions and that may also be helpful for future development of computational methods. The researchers used an established set of human melanoma cell lines to evaluate the performance of 60-mer arrays (Agilent, Nimblegen) and SNP oligonucleotide arrays (Affymetrix). They examined the ability of the different platforms to detect low-amplitude (2-fold copy number gain or loss) CNAs or focal high-amplitude CNAs. The results from the comparison to detect low-amplitude CNAs showed that Agilent-optimized CGH arrays provided the most reproducible replicate hybridizations (Table 1), the most robust detection (Table 2), and highest specificity (Figure 1) when detecting low amplitude aberrations. The results from the comparison to detect focal high-amplitude CNAs showed that successful detection of focal events relies on high-density probe coverage.
Table 1. Reproducibility measured by correlation between duplicate hybridizations.
Table 2. Absolute signals and signal to noise for 2-fold copy number alteration.
Figure 1. The sensitivity and specificity of each copy number platform seems related to both probe spacing and length. A, top, given an optimized ratio threshold for identifying aberrant probes, the AG185K classified the fewest probes incorrectly when comparing regions of 4n and 2n in the melanoma cell line Lu1205, whereas the NG1500K had the highest degree of overlap in probe values between these regions; bottom, the platform-wise trends were similar when comparing a heterozygous loss with a 2n region in WM1366. B, ROC analysis of a copy number gain (Lu1205) and loss (WM1366) across a range of ratio thresholds shows that the AG44K and AG185K chips most readily distinguished aberrant from non-aberrant probes. Both SNP chips were intermediate to the Agilent and NimbleGen assays.
Title: A Comparison of DNA Copy Number Profiling Platforms.
Authors: Greshock J, Feng B, Nogueira C, Ivanova E, Perna I, Nathanson K, Protopopov A, Weber BL, Chin L
Journal: Cancer Res. 2007 Nov 1;67(21):10173-80. Epub 2007 Oct 29.
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