Significance analysis of microarrays applied to the ionizing radiation response
Significance analysis of microarrays applied to the ionizing radiation response
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DOI：
10.1073/pnas.091062498
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发表时间：
2001-04-24
影响因子：
11.1
通讯作者：
Chu, G
中科院分区：
文献类型：
--
作者：
Tusher, VG;Tibshirani, R;Chu, G
微阵列可以测量数千个基因的表达，以识别不同生物状态之间的表达变化。需要方法来确定这些变化的意义，同时考虑到大量的基因。我们描述了一种方法，微阵列的显著性分析（SAM）。它根据基因表达的变化相对于重复测量的标准差来给每个基因打分。对于得分大于可调整阈值的基因。SAM使用重复测量的排列来估计偶然识别的基因的百分比，即错误发现率（FDR）。当人类细胞对电离辐射的转录反应被微阵列测量时。SAM确定了34个基因，其变化至少为1.5倍，估计FDR为12%。与使用常规分析方法的60%和84%的FDR相比。在34个基因中，19个参与细胞周期调控，3个参与细胞凋亡。令人惊讶的是，4个核苷酸切除修复基因被诱导，这表明该修复途径可能在电离辐射损伤的DNA修复中发挥先前未被认识的作用。
Microarrays can measure the expression of thousands of genes to identify changes in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. We describe a method, Significance Analysis of Microarrays (SAM). that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements. For genes with scores greater than an adjustable threshold. SAM uses permutations of the repeated measurements to estimate the percentage of genes identified by chance, the false discovery rate (FDR). When the transcriptional response of human cells to ionizing radiation was measured by microarrays. SAM identified 34 genes that changed at least 1.5-fold with an estimated FDR of 12%. compared with FDRs of 60 and 84% by using conventional methods of analysis. Of the 34 genes, 19 were involved in cell cycle regulation and 3 in apoptosis, Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.