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A Bayesian Partition Method for Detecting Pleiotropic and Epistatic eQTL Modules

机译:用于检测多效性和上位性eQTL模块的贝叶斯划分方法

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摘要

Studies of the relationship between DNA variation and gene expression variation, often referred to as “expression quantitative trait loci (eQTL) mapping”, have been conducted in many species and resulted in many significant findings. Because of the large number of genes and genetic markers in such analyses, it is extremely challenging to discover how a small number of eQTLs interact with each other to affect mRNA expression levels for a set of co-regulated genes. We present a Bayesian method to facilitate the task, in which co-expressed genes mapped to a common set of markers are treated as a module characterized by latent indicator variables. A Markov chain Monte Carlo algorithm is designed to search simultaneously for the module genes and their linked markers. We show by simulations that this method is more powerful for detecting true eQTLs and their target genes than traditional QTL mapping methods. We applied the procedure to a data set consisting of gene expression and genotypes for 112 segregants of S. cerevisiae. Our method identified modules containing genes mapped to previously reported eQTL hot spots, and dissected these large eQTL hot spots into several modules corresponding to possibly different biological functions or primary and secondary responses to regulatory perturbations. In addition, we identified nine modules associated with pairs of eQTLs, of which two have been previously reported. We demonstrated that one of the novel modules containing many daughter-cell expressed genes is regulated by AMN1 and BPH1. In conclusion, the Bayesian partition method which simultaneously considers all traits and all markers is more powerful for detecting both pleiotropic and epistatic effects based on both simulated and empirical data.
机译:DNA变异与基因表达变异之间的关系的研究(通常称为“表达数量性状基因座(eQTL)作图”)已在许多物种中进行,并产生了许多重要发现。由于此类分析中存在大量基因和遗传标记,因此发现少量eQTL如何相互作用以影响一组共同调控的基因的mRNA表达水平极具挑战性。我们提出一种贝叶斯方法来简化任务,其中映射到一组共同标记的共表达基因被视为以潜在指标变量为特征的模块。设计了马尔可夫链蒙特卡洛算法,以同时搜索模块基因及其链接的标记。通过仿真显示,与传统的QTL定位方法相比,该方法对检测真正的eQTL及其目标基因更有效。我们将该程序应用于由S.cerevisiae的112个分离子的基因表达和基因型组成的数据集。我们的方法确定了包含映射到先前报道的eQTL热点的基因的模块,并将这些大的eQTL热点分解为几个模块,这些模块对应于可能不同的生物学功能或对调节扰动的主要和次要反应。此外,我们确定了与eQTL对相关的9个模块,其中2个先前已报告过。我们证明,包含许多子细胞表达基因的新型模块之一受AMN1和BPH1调控。总之,同时考虑所有特征和所有标记的贝叶斯划分方法对于基于模拟和经验数据的多效性和上位性效应检测都更为有效。

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