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适用于高度尖峰数据的自适应局部假发现率程序及其在酵母 SET4 缺失突变体 RNA 测序数据中的应用。

Adaptive local false discovery rate procedures for highly spiky data and their application RNA sequencing data of yeast SET4 deletion mutants.

机构信息

Department of Mathematics and Statistics, University of Maryland, Baltimore County, Baltimore, MD, USA.

Department of Mathematics and Physics, University of Santo Tomas, Manila, Philippines.

出版信息

Biom J. 2021 Dec;63(8):1729-1744. doi: 10.1002/bimj.202000256. Epub 2021 Jul 28.

Abstract

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 mutant dataset) compared to the wild-type yeast cells. The Set4 mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 mutant dataset.

摘要

染色质动力学是基因表达和基因组稳定性调控的核心。为了更好地理解调控染色质动力学的因素,我们会删除编码这些因素的基因,并使用 RNA 测序等方法确定差异基因表达谱。在这里,我们分析了一个旨在揭示相对未被表征的染色质调节因子 Set4 在模式生物酿酒酵母中的功能的基因表达数据集。本文的主要主题集中在识别 Set4 缺失(称为 Set4 突变数据集)的细胞中高度差异表达的基因与野生型酵母细胞相比。Set4 突变数据在其表达的对数倍变化上产生了一个尖峰分布,并且可以合理地假设,那些不是高度差异表达的基因来自两个正态分布的混合。我们提出了一种自适应局部假发现率(FDR)程序,该程序通过经验估计对数倍变化的零分布。我们数值表明,与现有方法不同,我们提出的方法可以在目标 FDR(0.05)水平上进行控制,并且在发现差异表达基因方面也具有竞争力。最后,我们将我们的方法应用于分析 Set4 突变数据集。

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本文引用的文献

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FALSE DISCOVERY RATE ANALYSIS OF BRAIN DIFFUSION DIRECTION MAPS.脑扩散方向图的错误发现率分析
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SET domains and stress: uncovering new functions for yeast Set4.SET 结构域和应激:揭示酵母 Set4 的新功能。
Curr Genet. 2019 Jun;65(3):643-648. doi: 10.1007/s00294-018-0917-6. Epub 2018 Dec 6.
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