Skvortsov Dmitriy, Abdueva Diana, Stitzer Michael E, Finkel Steven E, Tavaré Simon
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
BMC Bioinformatics. 2007 Jun 14;8:203. doi: 10.1186/1471-2105-8-203.
The sequencing of many genomes and tiling arrays consisting of millions of DNA segments spanning entire genomes have made high-resolution copy number analysis possible. Microarray-based comparative genomic hybridization (array CGH) has enabled the high-resolution detection of DNA copy number aberrations. While many of the methods and algorithms developed for the analysis microarrays have focused on expression analysis, the same technology can be used to detect genetic alterations, using for example standard commercial Affymetrix arrays. Due to the nature of the resultant data, standard techniques for processing GeneChip expression experiments are inapplicable.
We have developed a robust and flexible methodology for high-resolution analysis of DNA copy number of whole genomes, using Affymetrix high-density expression oligonucleotide microarrays. Copy number is obtained from fluorescence signals after processing with novel normalization, spatial artifact correction, data transformation and deletion/duplication detection. We applied our approach to identify deleted and amplified regions in E. coli mutants obtained after prolonged starvation.
The availability of Affymetrix expression chips for a wide variety of organisms makes the proposed array CGH methodology useful more generally.
对许多基因组进行测序以及使用由数百万跨越整个基因组的DNA片段组成的平铺阵列，使得高分辨率拷贝数分析成为可能。基于微阵列的比较基因组杂交（阵列CGH）能够高分辨率检测DNA拷贝数畸变。虽然为分析微阵列开发的许多方法和算法都集中在表达分析上，但同样的技术可用于检测基因改变，例如使用标准的商业Affymetrix阵列。由于所得数据的性质，处理基因芯片表达实验的标准技术并不适用。
我们开发了一种强大且灵活的方法，用于使用Affymetrix高密度表达寡核苷酸微阵列对全基因组的DNA拷贝数进行高分辨率分析。通过新颖的归一化、空间伪影校正、数据转换和缺失/重复检测处理后，从荧光信号中获得拷贝数。我们应用我们的方法来鉴定长时间饥饿后获得的大肠杆菌突变体中的缺失和扩增区域。
Affymetrix表达芯片可用于多种生物体，这使得所提出的阵列CGH方法更具通用性。
