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基于阵列比较基因组杂交的DNA拷贝数变异的改进统计分析

Improved Statistical Analysis for Array CGH-Based DNA Copy Number Aberrations.

作者信息

Jiang Hongmei, Zhu Zhong-Zheng, Yu Yue, Lin Simon, Hou Lifang

机构信息

Department of Statistics, Northwestern University, 2006 Sheridan Road, Evanston, IL 60208, USA.

出版信息

Cancer Inform. 2011;10:249-58. doi: 10.4137/CIN.S8019. Epub 2011 Oct 19.

DOI:10.4137/CIN.S8019
PMID:22084565
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3212864/
Abstract

Array-based comparative genomic hybridization (aCGH) allows measuring DNA copy number at the whole genome scale. In cancer studies, one may be interested in identifying DNA copy number aberrations (CNAs) associated with certain clinicopathological characteristics such as cancer metastasis. We proposed to define test regions based on copy number pattern profiles across multiple samples, using either smoothed log(2)-ratio or discrete data of copy number gain/loss calls. Association test performed on the refined test regions instead of the probes has improved power due to reduced number of tests. We also compared three types of measurement of copy number levels, normalized log(2)-ratio, smoothed log(2)-ratio, and copy number gain or loss calls in statistical hypothesis testing. The relative strengths and weaknesses of the proposed method were demonstrated using both simulation studies and real data analysis of a liver cancer study.

摘要

基于微阵列的比较基因组杂交（aCGH）能够在全基因组范围内测量DNA拷贝数。在癌症研究中，人们可能有兴趣识别与某些临床病理特征（如癌症转移）相关的DNA拷贝数变异（CNA）。我们建议根据多个样本的拷贝数模式概况来定义测试区域，使用平滑后的log(2)比率或拷贝数增加/缺失调用的离散数据。由于测试数量减少，在精炼后的测试区域而非探针上进行的关联测试提高了检验效能。我们还在统计假设检验中比较了三种拷贝数水平的测量方法，即标准化log(2)比率、平滑log(2)比率以及拷贝数增加或缺失调用。通过模拟研究和一项肝癌研究的真实数据分析，证明了所提出方法的相对优缺点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/c9aa24bce5f5/cin-10-2011-249f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/c1cdc977f3a7/cin-10-2011-249f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/49b11364d85f/cin-10-2011-249f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/05768a7ea634/cin-10-2011-249f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/c9aa24bce5f5/cin-10-2011-249f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/c1cdc977f3a7/cin-10-2011-249f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/49b11364d85f/cin-10-2011-249f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/05768a7ea634/cin-10-2011-249f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/250b/3212864/c9aa24bce5f5/cin-10-2011-249f4.jpg

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