Experimental design for three-color and four-color gene expression microarrays

Experimental design for three-color and four-color gene expression microarrays
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DOI:
10.1093/bioinformatics/bti1031
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发表时间:
2005-06-01
期刊:
影响因子:
5.8
通讯作者:
Churchill, G
Churchill, G
中科院分区:
生物学3区
文献类型:
--
作者:
Woo, Y;Krueger, W;Churchill, G

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动机:与双色微阵列相比,三色微阵列可以提高设计效率和检测差异表达的能力,而无需额外的样品和阵列。此外,三色微阵列技术目前可以以合理的成本获得。尽管有潜在的优势,但设计和分析三色实验的明确指导方针并不存在。结果如下:我们提出了一个三色和四色循环设计(循环)和互补的图形表示,以帮助设计实验,是平衡的,高效的和强大的杂交失败。理论上,三色环设计比双色环设计更有效。使用两种和三种颜色平台的实验平行进行,并在R/MAANOVA中使用线性混合模型分析来分析其输出。这些结果表明,使用相同数量的样本(和更少的阵列)的三色实验将与双色实验一样有效。改进的设计效率在某种程度上被三色实验系统中减小的动态范围和增加的可变性所抵消。这一结果表明,通过微小的技术改进,使用环设计的三色微阵列可以比双色环设计更有效地检测差异表达。
Motivation: Three-color microarrays, compared with two-color microarrays, can increase design efficiency and power to detect differential expression without additional samples and arrays. Furthermore, three-color microarray technology is currently available at a reasonable cost. Despite the potential advantages, clear guidelines for designing and analyzing three-color experiments do not exist. Results: We propose a three-and a four-color cyclic design ( loop) and a complementary graphical representation to help design experiments that are balanced, efficient and robust to hybridization failures. In theory, three-color loop designs are more efficient than two-color loop designs. Experiments using both two- and three-color platforms were performed in parallel and their outputs were analyzed using linear mixed model analysis in R/MAANOVA. These results demonstrate that three-color experiments using the same number of samples (and fewer arrays) will perform as efficiently as two- color experiments. The improved efficiency of the design is somewhat offset by a reduced dynamic range and increased variability in the three-color experimental system. This result suggests that, with minor technological improvements, three-color microarrays using loop designs could detect differential expression more efficiently than two-color loop designs.