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共显性和上位性的联合分析(CAPE)。

The Combined Analysis of Pleiotropy and Epistasis (CAPE).

机构信息

The Jackson Laboratory, Bar Harbor, ME, USA.

出版信息

Methods Mol Biol. 2021;2212:55-67. doi: 10.1007/978-1-0716-0947-7_5.

Abstract

Epistasis, or gene-gene interaction, contributes substantially to trait variation in organisms ranging from yeast to humans, and modeling epistasis directly is critical to understanding the genotype-phenotype map. However, inference of genetic interactions is challenging compared to inference of individual allele effects due to low statistical power. Furthermore, genetic interactions can appear inconsistent across different quantitative traits, presenting a challenge for the interpretation of detected interactions. Here we present a method called the Combined Analysis of Pleiotropy and Epistasis (CAPE) that combines information across multiple quantitative traits to infer directed epistatic interactions. By combining information across multiple traits, CAPE not only increases power to detect genetic interactions but also interprets these interactions across traits to identify a single interaction that is consistent across all observed data. This method generates informative, interpretable interaction networks that explain how variants interact with each other to influence groups of related traits. This method could potentially be used to link genetic variants to gene expression, physiological endophenotypes, and higher-level disease traits.

摘要

上位性,或基因-基因相互作用,对从酵母到人类等生物的性状变异有很大的贡献,直接对上位性建模对于理解基因型-表型图谱至关重要。然而,与单个等位基因效应的推断相比,由于统计能力较低,遗传相互作用的推断具有挑战性。此外,遗传相互作用在不同的数量性状之间可能不一致,这对检测到的相互作用的解释提出了挑战。在这里,我们提出了一种称为多效性和上位性联合分析(CAPE)的方法,该方法结合了多个数量性状的信息来推断有向上位性相互作用。通过结合多个性状的信息,CAPE 不仅增加了检测遗传相互作用的能力,而且还可以在多个性状之间解释这些相互作用,以识别在所有观察到的数据中一致的单个相互作用。该方法生成了信息丰富且可解释的相互作用网络,解释了变体如何相互作用以影响相关性状组。该方法可能用于将遗传变异与基因表达、生理内表型和更高层次的疾病特征联系起来。

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