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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Application of genome-wide expression analysis to human health and disease
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Application of genome-wide expression analysis to human health and disease

机译：全基因组表达分析在人类健康和疾病中的应用

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摘要

The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysts with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.
机译：将全基因组表达分析应用于重症患者的大规模，多中心计划带来了许多理论和技术挑战。我们在这里描述了一种分析和组织方法，用于系统评估与专为研究人类疾病而设计的全基因组表达分析相关的方差。我们分析了用商业寡核苷酸阵列进行的全基因组表达分析的差异来源。此外，还研究了在同一受试者，不同健康受试者之间，不同白细胞亚群之间重复采样导致的人类血液白细胞基因表达的差异，以及创伤性损伤的影响。我们报告说，样品处理引起的分析差异很小。同一个人在24小时内的血液白细胞基因表达非常稳定。相反，不同受试者和白细胞亚群之间的全基因组表达差异显着。可以预期的是，外伤引起的表观基因表达发生了巨大变化，其幅度大于分析噪声和个体差异。我们证明开发针对基因表达分析人员的全国性计划时要特别注意分析细节，可以将临床环境中的差异降低到一个水平，在该水平上，不同健康人类受试者之间的基因表达模式可以提供有益的信息，并且可以通过以下方法进行研究：对人类疾病的信心。

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