CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays
CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays
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DOI：
10.1186/1471-2105-7-83
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发表时间：
2006-02-21
影响因子：
3
通讯作者：
Shapero, MH
中科院分区：
文献类型：
--
作者：
Huang, J;Wei, W;Shapero, MH
背景：DNA拷贝数改变是癌细胞核型的主要特征之一，可以有助于这些细胞的复杂表型。这些改变会导致细胞癌基因的增长以及肿瘤抑制基因的损失，并且可以跨越较小的间隔，并且涉及整个染色体。准确检测这些变化的能力对于理解它们如何影响细胞的生物学是至关重要的：我们描述了一种使用探针强度信息来推断等位基因副本的新型算法（带回归和树的副本分析）（复制号分析） - 高密度DNA寡核苷酸阵列的特异性方式设计为超过100,000个SNP的基因型。使用CARAT的总和特定于等位基因的拷贝数估计是使用定量PCR和等位基因Taqman反应与几种人类乳腺癌细胞系的定量PCR和等位基因Taqman反应独立评估SNP的。使用包含不同数量的X染色体和正常个体的测试集的DNA样品来表征算法的灵敏度和特异性。该算法的结果与独立验证方法的结果相同。结论：总体而言，Carat自动检测具有拷贝数变化的区域，并为每个变化分配显着性得分，并生成等位基因特异性输出。当与来自同一阵列的SNP基因型调用结合时，Carat为基因组宽改变的结构提供了更多细节，这可能导致等位基因失衡。
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.Conclusion: 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.