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一种用于分析甲基化和基因表达数据的强大统一方法。

A Robust Unified Approach to Analyzing Methylation and Gene Expression Data.

作者信息

Khalili Abbas, Huang Tim, Lin Shili

机构信息

Department of Statistics, The Ohio State University, Columbus, OH 43210, United States.

出版信息

Comput Stat Data Anal. 2009 Mar 15;53(5):1701-1710. doi: 10.1016/j.csda.2008.07.010.

Abstract

Microarray technology has made it possible to investigate expression levels, and more recently methylation signatures, of thousands of genes simultaneously, in a biological sample. Since more and more data from different biological systems or technological platforms are being generated at an incredible rate, there is an increasing need to develop statistical methods that are applicable to multiple data types and platforms. Motivated by such a need, a flexible finite mixture model that is applicable to methylation, gene expression, and potentially data from other biological systems, is proposed. Two major thrusts of this approach are to allow for a variable number of components in the mixture to capture non-biological variation and small biases, and to use a robust procedure for parameter estimation and probe classification. The method was applied to the analysis of methylation signatures of three breast cancer cell lines. It was also tested on three sets of expression microarray data to study its power and type I error rates. Comparison with a number of existing methods in the literature yielded very encouraging results; lower type I error rates and comparable/better power were achieved based on the limited study. Furthermore, the method also leads to more biologically interpretable results for the three breast cancer cell lines.

摘要

微阵列技术使得在生物样本中同时研究数千个基因的表达水平以及最近的甲基化特征成为可能。由于来自不同生物系统或技术平台的数据正以惊人的速度不断产生,因此越来越需要开发适用于多种数据类型和平台的统计方法。出于这种需求,我们提出了一种灵活的有限混合模型,该模型适用于甲基化、基因表达以及可能来自其他生物系统的数据。这种方法的两个主要要点是允许混合物中的成分数量可变,以捕获非生物学变异和小偏差,并使用稳健的程序进行参数估计和探针分类。该方法被应用于分析三种乳腺癌细胞系的甲基化特征。它还在三组表达微阵列数据上进行了测试,以研究其功效和I型错误率。与文献中许多现有方法的比较产生了非常令人鼓舞的结果;基于有限的研究,实现了更低的I型错误率和相当/更好的功效。此外,该方法还为三种乳腺癌细胞系带来了更具生物学解释性的结果。

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