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A permutation-based multiple testing method for time-course microarray experiments

机译:基于排列的时程微阵列实验的多重测试方法

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Background Time-course microarray experiments are widely used to study the temporal profiles of gene expression. Storey et al . (2005) developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression trajectories change over time within a single biological group, or those that follow different time trajectories among multiple groups. They estimated the expression trajectories of each gene using natural cubic splines under the null (no time-course) and alternative (time-course) hypotheses, and used a goodness of fit test statistic to quantify the discrepancy. The null distribution of the statistic was approximated through a bootstrap method. Gene expression levels in microarray data are often complicatedly correlated. An accurate type I error control adjusting for multiple testing requires the joint null distribution of test statistics for a large number of genes. For this purpose, permutation methods have been widely used because of computational ease and their intuitive interpretation. Results In this paper, we propose a permutation-based multiple testing procedure based on the test statistic used by Storey et al . (2005). We also propose an efficient computation algorithm. Extensive simulations are conducted to investigate the performance of the permutation-based multiple testing procedure. The application of the proposed method is illustrated using the Caenorhabditis elegans dauer developmental data. Conclusion Our method is computationally efficient and applicable for identifying genes whose expression levels are time-dependent in a single biological group and for identifying the genes for which the time-profile depends on the group in a multi-group setting.
机译:背景技术时程微阵列实验被广泛用于研究基因表达的时间分布。 Storey等。 (2005)开发了一种分析时程微阵列研究的方法,该方法可用于发现在单个生物组中表达轨迹随时间变化或在多个生物组中遵循不同时间轨迹的基因。他们在零假设(无时间过程)和替代假设(时间过程)下使用自然三次样条估计了每个基因的表达轨迹,并使用拟合检验统计量来量化差异。统计量的零分布通过引导方法进行近似。微阵列数据中的基因表达水平通常复杂地相关。针对多种测试进行调整的准确的I型错误控制需要对大量基因的测试统计数据进行联合零分布。为此目的,由于计算的容易性和直观的解释,置换方法已被​​广泛使用。结果在本文中,我们基于Storey等人使用的测试统计数据,提出了一种基于排列的多重测试程序。 (2005)。我们还提出了一种有效的计算算法。进行了广泛的仿真,以研究基于排列的多重测试程序的性能。利用秀丽隐杆线虫发育数据说明了该方法的应用。结论我们的方法计算效率高,适用于在单个生物组中鉴定表达水平与时间相关的基因,以及在多组环境中鉴定时间谱依赖于该组的基因。

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