An associative analysis of gene expression array data
An associative analysis of gene expression array data
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DOI：
10.1093/bioinformatics/19.2.204
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发表时间：
2003-01-22
期刊：
影响因子：
5.8
通讯作者：
Centola, M
中科院分区：
文献类型：
--
作者：
Dozmorov, I;Centola, M
动机：我们面临着缺乏优化标准来指导数据集的规范化、比较分析和解释。其中一个方面是，目前的统计分析方法没有充分利用固有的信息在大的数据集中产生的微阵列实验和需要检测灵敏度和特异性之间的权衡结果：我们提出了一个多步骤的程序从cDNA阵列方法获得的mRNA表达数据的分析。为了识别和分类差异表达的基因，将标准化数据的标准配对t检验结果与一种新方法（称为关联分析）的结果进行比较。该方法将实验基因表达作为残差在回归分析中对控制平均表达的一个共同的标准-家庭的类似计算的残差来自控制实验的低变异性基因。通过将给定基因的表达变化与对照组的大量同等表达基因相关联，该方法利用微阵列实验中固有的大数据集来增加特异性和灵敏度。整个过程通过其表达在Snell侏儒小鼠（dw/dw）和其表型正常的同窝出生小鼠（dw/+，+/+）之间显著不同的基因的列表来说明。在检测的2352个基因中，只有450-500个基因的表达高于在非表达基因中观察到的背景水平，并且其中120个基因在排除假阳性测定出现的显著性水平上被确定为在侏儒小鼠中差异表达。
Motivation: We face the absence of optimized standards to guide normalization, comparative analysis, and interpretation of data sets. One aspect of this is that current methods of statistical analysis do not adequately utilize the information inherent in the large data sets generated in a microarray experiment and require a tradeoff between detection sensitivity and specificity.Results: We present a multistep procedure for analysis of mRNA expression data obtained from cDNA array methods. To identify and classify differentially expressed genes, results from standard paired t-test of normalized data are compared with those from a novel method, denoted an associative analysis. This method associates experimental gene expressions presented as residuals in regression analysis against control averaged expressions to a common standard-the family of similarly computed residuals for low variability genes derived from control experiments. By associating changes in expression of a given gene to a large family of equally expressed genes of the control group, this method utilizes the large data sets inherent in microarray experiments to increase both specificity and sensitivity. The overall procedure is illustrated by tabulation of genes whose expression differs significantly between Snell dwarf mice (dw/dw) and their phenotypically normal littermates (dw/+, +/+). Of the 2352 genes examined only 450-500 were expressed above the background levels observed in nonexpressed genes and of these 120 were established as differentially expressed in dwarf mice at a significance level that excludes appearance of false positive determinations.Contact: igor-dozmorov@omrf.ouhsc.edu.