A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays
A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays
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DOI：
10.1158/0008-5472.can-05-0465
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发表时间：
2005-07-15
期刊：
影响因子：
11.2
通讯作者：
Ogawa, S
中科院分区：
文献类型：
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作者：
Nannya, Y;Sanada, M;Ogawa, S
我们使用含有116,204个单核苷酸多态性的高密度寡核苷酸微阵列开发了一种可靠的算法，用于对人基因组进行拷贝数分析。该算法的优点包括提高信噪比（S/N）比和使用优化的参考。通过考虑使用二次回归的PCR产品的长度和GC含量来提高原始S/N比率。宪法DNA的使用（如果可用）可提供最低的SD值（0.16 +/- 0.03），并且还可以在癌症基因组中基于等位基因的拷贝数检测，这可能会揭示其他隐藏的等位基因失衡。在没有宪法DNA的情况下，优化了具有最高S/N比的多个正常参考，结合数据回归，将SD值从0.67 +/- 0.12升至0.18 +/- 0.03。这些改进可以高度可靠地比较不同的实验条件下的数据，基于等位基因的拷贝数变化的检测以及对拷贝数畸变的范围和幅度的更准确估计。该算法已在称为Affymetrix Genechip映射100K阵列（CNAG）的称为复制号分析仪的软件包中实现。总体而言，这些增强功能使CNAG成为高分辨率检测拷贝数变化的有用工具，这些工具可以帮助理解癌症和其他疾病的发病机理以及探索人类基因组的复杂性。
We have developed a robust algorithm for copy number analysis of the human genome using high-density oligonucleotide microarrays containing 116,204 single-nucleotide polymorphisms. The advantages of this algorithm include the improvement of signal-to-noise (S/N) ratios and the use of an optimized reference. The raw S/N ratios were improved by accounting for the length and GC content of the PCR products using quadratic regressions. The use of constitutional DNA, when available, gives the lowest SD values (0.16 +/- 0.03) and also enables allele-based copy number detection in cancer genomes, which can unmask otherwise concealed allelic imbalances. In the absence of constitutional DNA, optimized selection of multiple normal references with the highest S/N ratios, in combination with the data regressions, dramatically improves SD values from 0.67 +/- 0.12 to 0.18 +/- 0.03. These improvements allow for highly reliable comparison of data across different experimental conditions, detection of allele-based copy number changes, and more accurate estimations of the range and magnitude of copy number aberrations. This algorithm has been implemented in a software package called Copy Number Analyzer for Affymetrix GeneChip Mapping 100K arrays (CNAG). Overall, these enhancements make CNAG a useful tool for high-resolution detection of copy number alterations which can help in the understanding of the pathogenesis of cancers and other diseases as well as in exploring the complexities of the human genome.