Genetic risk prediction using a spatial autoregressive model with adaptive lasso.

Genetic risk prediction using a spatial autoregressive model with adaptive lasso.
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使用具有自适应套索的空间自回归模型进行遗传风险预测

DOI:
10.1002/sim.7832
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发表时间:
2018-11-20
影响因子:
2
通讯作者:
Lu Q
Lu Q
中科院分区:
医学3区
文献类型:
--
作者:
Wen Y;Shen X;Lu Q

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随着高通量技术的快速发展,正在启动研究,以加速精准医学的进程。大量测序数据的收集为我们系统地研究测序变体的深度目录在风险预测中的作用提供了很好的机会。然而,测序数据中大量的噪声信号和低频率的罕见变异对风险预测建模提出了巨大的分析挑战。受空间统计学发展的启发,我们提出了一个具有自适应套索的空间自回归模型(SARAL),用于使用高维测序数据进行风险预测建模。SARAL是一种基于集合的方法,因此,它减少了数据维度,并在单核苷酸变异(SNV)集合内积累遗传效应。此外,它允许不同的SNV集具有不同的幅度和方向的效果大小,这反映了复杂疾病的性质。通过自适应套索的实现,SARAL可以将噪声SNV集的影响缩小到零,从而进一步提高预测精度。通过模拟研究,我们证明,总体而言,SARAL是可比的,如果不是更好的,基因组最佳线性无偏预测方法。该方法进一步说明了应用程序的测序数据从阿尔茨海默氏病神经影像倡议。
With rapidly evolving high-throughput technologies, studies are being initiated to accelerate the process toward precision medicine. The collection of the vast amounts of sequencing data provides us with great opportunities to systematically study the role of a deep catalog of sequencing variants in risk prediction. Nevertheless, the massive amount of noise signals and low frequencies of rare variants in sequencing data pose great analytical challenges on risk prediction modeling. Motivated by the development in spatial statistics, we propose a spatial autoregressive model with adaptive lasso (SARAL) for risk prediction modeling using high-dimensional sequencing data. The SARAL is a set-based approach, and thus, it reduces the data dimension and accumulates genetic effects within a single-nucleotide variant (SNV) set. Moreover, it allows different SNV sets having various magnitudes and directions of effect sizes, which reflects the nature of complex diseases. With the adaptive lasso implemented, SARAL can shrink the effects of noise SNV sets to be zero and, thus, further improve prediction accuracy. Through simulation studies, we demonstrate that, overall, SARAL is comparable to, if not better than, the genomic best linear unbiased prediction method. The method is further illustrated by an application to the sequencing data from the Alzheimer’s Disease Neuroimaging Initiative.
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