A weighted empirical Bayes risk prediction model using multiple traits.

Pub Date : 2020-09-04 DOI:10.1515/sagmb-2019-0056
Gengxin Li, Lin Hou, Xiaoyu Liu, Cen Wu
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Abstract

With rapid advances in high-throughput sequencing technology, millions of single-nucleotide variants (SNVs) can be simultaneously genotyped in a sequencing study. These SNVs residing in functional genomic regions such as exons may play a crucial role in biological process of the body. In particular, non-synonymous SNVs are closely related to the protein sequence and its function, which are important in understanding the biological mechanism of sequence evolution. Although statistically challenging, models incorporating such SNV annotation information can improve the estimation of genetic effects, and multiple responses may further strengthen the signals of these variants on the assessment of disease risk. In this work, we develop a new weighted empirical Bayes method to integrate SNV annotation information in a multi-trait design. The performance of this proposed model is evaluated in simulation as well as a real sequencing data; thus, the proposed method shows improved prediction accuracy compared to other approaches.

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多特征加权经验贝叶斯风险预测模型。
随着高通量测序技术的快速发展,在测序研究中可以同时对数百万个单核苷酸变异(snv)进行基因分型。这些存在于功能基因组区域(如外显子)的snv可能在机体的生物学过程中起着至关重要的作用。其中,非同义snv与蛋白质序列及其功能密切相关,对理解序列进化的生物学机制具有重要意义。尽管在统计上具有挑战性,但纳入此类SNV注释信息的模型可以改善对遗传效应的估计,并且多重反应可能进一步加强这些变异对疾病风险评估的信号。在这项工作中,我们开发了一种新的加权经验贝叶斯方法来整合多特征设计中的SNV注释信息。在仿真和实际测序数据中对该模型的性能进行了评价;因此,与其他方法相比,该方法具有更高的预测精度。
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