Eraly Satish A
Department of Medicine, University of California San Diego, School of Medicine, La Jolla, California, United States of America.
PLoS One. 2014 May 15;9(5):e97734. doi: 10.1371/journal.pone.0097734. eCollection 2014.
Microarray analyses of gene knockouts have traditionally focused on the identification of genes whose mean expression is different in knockout and wild-type mice. However, recent work suggests that changes in the variability of gene expression can have important phenotypic consequences as well. Here, in an unbiased sample of publicly available microarray data on gene expression in various knockouts, highly significant differences from wild-type (either increases or decreases) are noted in the gene expression coefficients of variation (CVs) of virtually every knockout considered. Examination of the distribution of gene-by-gene CV differences indicates that these findings are not attributable to a few outlier genes, but rather to broadly increased or decreased CV in the various knockouts over all the (tens of thousands of) transcripts assayed. These global differences in variability may reflect either authentic biological effects of the knockouts or merely experimental inconsistencies. However, regardless of the underlying explanation, the variability differences are of importance as they will influence both the statistical detection of gene expression changes and, potentially, the knockout phenotype itself.
传统上，基因敲除的微阵列分析主要集中于识别那些在基因敲除小鼠和野生型小鼠中平均表达存在差异的基因。然而，最近的研究表明，基因表达变异性的改变也可能产生重要的表型后果。在此，在一个关于各种基因敲除中基因表达的公开可用微阵列数据的无偏样本中，几乎在每一个被考虑的基因敲除的基因表达变异系数（CV）中都发现了与野生型的高度显著差异（无论是增加还是减少）。对逐个基因的CV差异分布的检查表明，这些发现并非归因于少数几个异常值基因，而是由于在所有（数以万计的）被检测转录本中，各种基因敲除的CV普遍增加或减少。这些变异性的全局差异可能反映了基因敲除的真实生物学效应，也可能仅仅是实验的不一致性。然而，无论潜在的解释如何，变异性差异都很重要，因为它们将影响基因表达变化的统计检测，并且可能影响基因敲除表型本身。
