Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays
Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays
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DOI：
10.1093/bioinformatics/bti133
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发表时间：
2005-04-01
期刊：
影响因子：
5.8
通讯作者：
Khan, J
中科院分区：
文献类型：
--
作者：
Bilke, S;Chen, QR;Khan, J
动机：基因组变异的积累是肿瘤形成和发展的重要过程。cDNA芯片比较基因组杂交（cDNAaCGH）是在全基因组范围内研究基因组变异的常用方法。然而，当检测到低水平的DNA拷贝数的变化，这种技术需要使用的降噪策略，由于低的信号噪声ratio.Results：目前运行平均平滑滤波器是最常用的降噪策略。我们从理论和实验上分析了这种策略，发现它对非常低水平的基因组改变不敏感。数据中存在系统误差是造成这一失败的主要原因之一。我们开发了一种新的算法，该算法有效地降低了系统噪声，并允许检测低水平的基因组改变。该算法是基于生物相关数据的比较，从所谓的自我自我杂交，额外的实验，其中不包含生物信息，但包含系统误差的数据。我们发现，与我们的算法的有效分辨率为+/- 1 DNA拷贝数的变化是约2 Mb。对于大于3的拷贝数变化，有效分辨率是在单个基因的水平上。
Motivation: The accumulation of genomic alterations is an important process in tumor formation and progression. Comparative genomic hybridization performed on cDNA arrays (cDNA aCGH) is a common method to investigate the genomic alterations on a genome-wide scale. However, when detecting low-level DNA copy number changes this technology requires the use of noise reduction strategies due to a low signal to noise ratio.Results: Currently a running average smoothing filter is the most frequently used noise reduction strategy. We analyzed this strategy theoretically and experimentally and found that it is not sensitive to very low level genomic alterations. The presence of systematic errors in the data is one of the main reasons for this failure. We developed a novel algorithm which efficiently reduces systematic noise and allows for the detection of low-level genomic alterations. The algorithm is based on comparison of the biological relevant data to data from so-called self-self hybridizations, additional experiments which contain no biological information but contain systematic errors. We find that with our algorithm the effective resolution for +/- 1 DNA copy number changes is about 2 Mb. For copy number changes larger than three the effective resolution is on the level of single genes.