Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms.
Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms.
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DOI：
10.1093/nar/gkn556
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发表时间：
2008-11
影响因子：
14.9
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Diskin SJ;Li M;Hou C;Yang S;Glessner J;Hakonarson H;Bucan M;Maris JM;Wang K
设计用于确定 DNA 拷贝数的具有大插入克隆的全基因组微阵列通常显示与克隆的基因组位置相关的杂交强度的变化。我们发现这些“基因组波”存在于 Illumina 和 Affymetrix SNP 基因分型芯片中，证实它们不是特定于平台的。基因组波的原因尚不清楚，它们可能会妨碍拷贝数变异 (CNV) 的准确推断。通过测量 1444 个样本的 DNA 浓度，并通过使用不同的 DNA 数量对同一样本进行多次基因分型，我们证明了 DNA 数量与波的强度相关。我们进一步表明，在考虑的多个基因组特征中，波状信号模式与 GC 含量最相关。为了测量波的强度，我们提出了 GC 波因子 (GCWF) 测量方法，它是 DNA 数量的可靠预测指标（基于连续稀释的样品，相关系数 = 0.994）。最后，我们开发了一种计算方法，通过拟合回归模型，并将 GC 含量作为预测变量，我们证明这种方法提高了 CNV 检测的准确性。随着全基因组SNP基因分型技术的广泛应用，我们的波调整方法对于充分利用基因分型样本进行CNV分析将具有重要意义。
Whole-genome microarrays with large-insert clones designed to determine DNA copy number often show variation in hybridization intensity that is related to the genomic position of the clones. We found these ‘genomic waves’ to be present in Illumina and Affymetrix SNP genotyping arrays, confirming that they are not platform-specific. The causes of genomic waves are not well-understood, and they may prevent accurate inference of copy number variations (CNVs). By measuring DNA concentration for 1444 samples and by genotyping the same sample multiple times with varying DNA quantity, we demonstrated that DNA quantity correlates with the magnitude of waves. We further showed that wavy signal patterns correlate best with GC content, among multiple genomic features considered. To measure the magnitude of waves, we proposed a GC-wave factor (GCWF) measure, which is a reliable predictor of DNA quantity (correlation coefficient = 0.994 based on samples with serial dilution). Finally, we developed a computational approach by fitting regression models with GC content included as a predictor variable, and we show that this approach improves the accuracy of CNV detection. With the wide application of whole-genome SNP genotyping techniques, our wave adjustment method will be important for taking full advantage of genotyped samples for CNV analysis.
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