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用于时间进程或剂量反应微阵列数据的经验贝叶斯基因筛选工具。

Empirical bayes gene screening tool for time-course or dose-response microarray data.

作者信息

Eckel J E, Gennings C, Chinchilli V M, Burgoon L D, Zacharewski T R

机构信息

Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia 23298, USA.

出版信息

J Biopharm Stat. 2004 Aug;14(3):647-70. doi: 10.1081/BIP-200025656.

Abstract

An efficient method to reduce the dimensionality of microarray gene expression data from thousands or tens of thousands of cDNA clones down to a subset of the most differentially expressed cDNA clones is essential in order to simplify the massive amount of data generated from microarray experiments. An extension to the methods of Efron et al. [Efron, B., Tibshirani, R., Storey, J., Tusher, V. (2001). Empirical Bayes analysis of a microarray experiment. J. Am. Statist. Assoc. 96:1151-1160] is applied to a differential time-course experiment to determine a subset of cDNAs that have the largest probability of being differentially expressed with respect to treatment conditions across a set of unequally spaced time points. The proposed extension, which is advocated to be a screening tool, allows for inference across a continuous variable in addition to incorporating a more complex experimental design and allowing for multiple design replications. With the current data the focus is on a time-course experiment; however, the proposed methods can easily be implemented on a dose-response experiment, or any other microarray experiment that contains a continuous variable of interest. The proposed empirical Bayes gene-screening tool is compared with the Efron et al. (2001) method in addition to an adjusted model-based t-value using a time-course data set where the toxicological effect of a specific mixture of chemicals is being studied.

摘要

为了简化从微阵列实验中生成的海量数据,必须有一种有效的方法将来自数千或数万个cDNA克隆的微阵列基因表达数据的维度降低到最具差异表达的cDNA克隆的一个子集。对Efron等人[Efron, B., Tibshirani, R., Storey, J., Tusher, V. (2001). Empirical Bayes analysis of a microarray experiment. J. Am. Statist. Assoc. 96:1151-1160]方法的一种扩展应用于一个差异时间进程实验,以确定在一组不等距时间点上相对于处理条件具有最大差异表达概率的cDNA子集。所提出的扩展方法被倡导作为一种筛选工具,除了纳入更复杂的实验设计并允许进行多次设计重复外,还允许对连续变量进行推断。就当前数据而言,重点是一个时间进程实验;然而,所提出的方法可以很容易地应用于剂量反应实验或任何其他包含感兴趣连续变量的微阵列实验。除了使用一个正在研究特定化学混合物毒理学效应的时间进程数据集的基于模型的调整t值外,还将所提出的经验贝叶斯基因筛选工具与Efron等人(2001)的方法进行了比较。

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