Bayesian Partition Models for Identifying Expression Quantitative Trait Loci.

Bayesian Partition Models for Identifying Expression Quantitative Trait Loci.
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DOI:
10.1080/01621459.2015.1049746
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发表时间:
2015
影响因子:
3.7
通讯作者:
Liu JS
Liu JS
中科院分区:
数学1区
文献类型:
--
作者:
Jiang B;Liu JS

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表达数量性状基因座(EQTL)是与特定基因表达水平变化相关的基因组位置。通过在全基因组范围内同时分析基因表达和遗传变异,科学家们希望发现负责一组基因表达变异的基因组位点。这项任务可以看作是一个多变量回归问题,在响应(基因表达)和协变量(遗传变异)上都有变量选择,还包括协变量之间的多路交互作用。我们没有学习给定遗传标记组合的数量性状预测模型,而是采用反向建模的观点来模拟基因表达特征条件下的遗传标记的分布。我们的方法的一个特别的优点是它能够检测到高功率的遗传变异的交互效应,即使它们的边缘效应很弱,解决了许多现有eQTL作图方法的一个关键弱点。此外,我们还引入了一个层次模型来捕捉相关基因之间的依赖结构。通过仿真研究和酵母中的真实数据实例,我们展示了我们的贝叶斯层次划分模型与现有方法相比,在检测eQTL方面取得了显著提高的能力。
Expression quantitative trait loci (eQTLs) are genomic locations associated with changes of expression levels of certain genes. By assaying gene expressions and genetic variations simultaneously on a genome-wide scale, scientists wish to discover genomic loci responsible for expression variations of a set of genes. The task can be viewed as a multivariate regression problem with variable selection on both responses (gene expression) and covariates (genetic variations), including also multi-way interactions among covariates. Instead of learning a predictive model of quantitative trait given combinations of genetic markers, we adopt an inverse modeling perspective to model the distribution of genetic markers conditional on gene expression traits. A particular strength of our method is its ability to detect interactive effects of genetic variations with high power even when their marginal effects are weak, addressing a key weakness of many existing eQTL mapping methods. Furthermore, we introduce a hierarchical model to capture the dependence structure among correlated genes. Through simulation studies and a real data example in yeast, we demonstrate how our Bayesian hierarchical partition model achieves a significantly improved power in detecting eQTLs compared to existing methods.
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