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arXiv 0803.3881stat.AP
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微阵列数据功能分类检验的统计框架

A statistical framework for testing functional categories in microarray data

William T. Barry, Andrew B. Nobel, Fred A. Wright

摘要:

对新兴的基因注释和功能途径数据库的快速访问已经将DNA微阵列研究中的差异表达评估从单个基因转移到具有共同生物学功能的基因组。本文对现有的评估一组基因(功能类别)差异表达的方法进行了批判性的审视,并提供了一些改进性能的建议。我们首先提出了一个一般的框架,其中一组基因的功能类别相比,互补的一组基因的阵列。该框架包括测试一系列重要基因中某一类别的过度表达,以及考虑差异表达的连续测量的方法。现有的测试分为两类。1类检验假设差异表达的基因特异性测量是独立的,尽管有压倒性的正相关证据。分析和模拟结果表明,1类测试是强烈的反保守的实践。第2类测试说明基因相关性,通常通过阵列排列,其通过构造对诱导的空值具有适当的第一类错误控制。然而,1类和2类检验均使用所有基因具有相同程度的差异表达的原假设。我们引入了一个更明智的和一般的(第3类)空下的微分表达式的配置文件是相同的范畴和补充。在这个更广泛的空值下,2类测试被证明是保守的。我们提出了标准的自举方法对3类空测试,并证明他们提供有效的第一类错误控制和更多的权力比阵列排列在模拟数据集和真正的微阵列实验。

英文摘要:

Ready access to emerging databases of gene annotation and functional pathways has shifted assessments of differential expression in DNA microarray studies from single genes to groups of genes with shared biological function. This paper takes a critical look at existing methods for assessing the differential expression of a group of genes (functional category), and provides some suggestions for improved performance. We begin by presenting a general framework, in which the set of genes in a functional category is compared to the complementary set of genes on the array. The framework includes tests for overrepresentation of a category within a list of significant genes, and methods that consider continuous measures of differential expression. Existing tests are divided into two classes. Class 1 tests assume gene-specific measures of differential expression are independent, despite overwhelming evidence of positive correlation. Analytic and simulated results are presented that demonstrate Class 1 tests are strongly anti-conservative in practice. Class 2 tests account for gene correlation, typically through array permutation that by construction has proper Type I error control for the induced null. However, both Class 1 and Class 2 tests use a null hypothesis that all genes have the same degree of differential expression. We introduce a more sensible and general (Class 3) null under which the profile of differential expression is the same within the category and complement. Under this broader null, Class 2 tests are shown to be conservative. We propose standard bootstrap methods for testing against the Class 3 null and demonstrate they provide valid Type I error control and more power than array permutation in simulated datasets and real microarray experiments.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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