Ratio statistics of gene expression levels and applications to microarray data analysis
Ratio statistics of gene expression levels and applications to microarray data analysis
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DOI：
10.1093/bioinformatics/18.9.1207
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发表时间：
2002-09-01
期刊：
影响因子：
5.8
通讯作者：
Trent, JM
中科院分区：
文献类型：
--
作者：
Chen, YD;Kamat, V;Trent, JM
动机：最近，由于cDNA微阵列的发展，大家族基因的基于表达的分析已经成为可能，该微阵列允许同时测量数千个基因的转录水平。对于微阵列上的每个点，必须从其背景中提取两个通道中的信号。这就需要算法来提取所产生的标记mRNA杂交到阵列cDNA locations和算法，以确定信号ratios.Results的意义的信号比率所产生的信号：本文侧重于估计从两个通道的信号比率，和这些比率的意义。关键问题是确定比率是显著高还是显著低，以便得出基因是上调还是下调的结论。本文建立在早期的研究，涉及假设检验的基础上的比率统计量的假设下，测量的荧光强度随后的图像处理可以被假定为反映信号强度。这里，考虑了一种改进的假设检验，其中假设形成比率的测量强度是信号和背景的组合。新方法涉及信噪比，并且对于高信噪比，新测试减少（接近近似）到原始测试。低信噪比对比值统计量的影响是本文的主题。最后，在这种情况下，制定了一个质量指标的斑点。此测量可用于决定是否应删除光点比率，或调整各种测量以反映测量质量的置信度。
Motivation: Expression-based analysis for large families of genes has recently become possible owing to the development of cDNA microarrays, which allow simultaneous measurement of transcript levels for thousands of genes. For each spot on a microarray, signals in two channels must be extracted from their backgrounds. This requires algorithms to extract signals arising from tagged mRNA hybridized to arrayed cDNA locations and algorithms to determine the significance of signal ratios.Results: This paper focuses on estimation of signal ratios from the two channels, and the significance of those ratios. The key issue is the determination of whether a ratio is significantly high or low in order to conclude whether the gene is upregulated or downregulated. The paper builds on an earlier study that involved a hypothesis test based on a ratio statistic under the supposition that the measured fluorescent intensities subsequent to image processing can be assumed to reflect the signal intensities. Here, a refined hypothesis test is considered in which the measured intensities forming the ratio are assumed to be combinations of signal and background. The new method involves a signal-to-noise ratio, and for a high signal-to-noise ratio the new test reduces (with close approximation) to the original test. The effect of low signal-to-noise ratio on the ratio statistics constitutes the main theme of the paper. Finally, and in this vein, a quality metric is formulated for spots. This measure can be used to decide whether or not a spot ratio should be deleted, or to adjust various measurements to reflect confidence in the quality of the measurement.