Tensor decomposition for multiple-tissue gene expression experiments.

Tensor decomposition for multiple-tissue gene expression experiments.
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DOI:
10.1038/ng.3624
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发表时间:
2016-09
期刊:
影响因子:
30.8
通讯作者:
Marchini, Jonathan
Marchini, Jonathan
中科院分区:
生物学1区
文献类型:
--
作者:
Hore, Victoria;Vinuela, Ana;Buil, Alfonso;Knight, Julian;McCarthy, Mark I.;Small, Kerrin;Marchini, Jonathan

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基因表达性状和其他细胞表型的全基因组关联研究已经成功地揭示了遗传变异和生物学过程之间的联系。大多数发现已经通过单因素单变量检验SNP对单个组织中基因表达的影响揭示了顺式eQTL效应。我们提出了一种贝叶斯方法,多组织实验的重点是揭示基因网络与遗传变异。我们的方法将基因表达测量的3D阵列(或张量)分解成一组潜在分量。我们识别稀疏基因网络,然后可以测试其与全基因组遗传变异的关联。我们将我们的方法应用于来自TwinsUK队列的845名个体的数据集,这些个体通过脂肪,LCL和皮肤中的RNA测序测量基因表达。我们发现了几个具有遗传基础和明确的生物学和统计学意义的基因网络。这种方法的扩展将允许多组学,环境和表型数据集的整合。
Genome wide association studies of gene expression traits and other cellular phenotypes have been successful in revealing links between genetic variation and biological processes. The majority of discoveries have uncovered cis eQTL effects via mass univariate testing of SNPs against gene expression in single tissues. We present a Bayesian method for multi-tissue experiments focusing on uncovering gene networks linked to genetic variation. Our method decomposes the 3D array (or tensor) of gene expression measurements into a set of latent components. We identify sparse gene networks, which can then be tested for association against genetic variation genome-wide. We apply our method to a dataset of 845 individuals from the TwinsUK cohort with gene expression measured via RNA sequencing in adipose, LCLs and skin. We uncover several gene networks with a genetic basis and clear biological and statistical significance. Extensions of this approach will allow integration of multi-omic, environmental and phenotypic datasets.
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