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arXiv 1201.5745stat.ME
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利用重叠群体Lasso快速识别与数量性状相关的生物途径

Fast Identification of Biological Pathways Associated with a Quantitative Trait Using Group Lasso with Overlaps

Matt Silver, Giovanni Montana

摘要:

在因果SNP(单核苷酸多态性)倾向于在生物学途径内积累的情况下,将先前的途径信息并入统计模型中预计将增加在遗传关联研究中检测真实关联的能力。大多数现有的基于路径的方法依赖于边际SNP统计,并没有充分利用路径内SNP之间的依赖模式。我们使用稀疏回归模型,与SNPs分组为途径,以确定因果关系的途径与数量性状。值得注意的功能,我们的“路径组套索与自适应权重”(P-GLAW)算法包括在一个单一的回归模型,自适应途径加权程序,占因素偏路径选择,并使用自举抽样程序的重要途径的排名的所有途径。P-GLAW考虑了重叠途径的存在,并使用一种新的技术组合来优化模型估计,使其即使在全基因组数据集上也能快速运行。在与基于单变量SNP统计的替代途径方法的比较研究中,我们的方法对于重要途径的检测表现出高灵敏度和特异性,在边际SNP效应大小小的情况下表现出最大的相对性能增益。

英文摘要:

Where causal SNPs (single nucleotide polymorphisms) tend to accumulate within biological pathways, the incorporation of prior pathways information into a statistical model is expected to increase the power to detect true associations in a genetic association study. Most existing pathways-based methods rely on marginal SNP statistics and do not fully exploit the dependence patterns among SNPs within pathways. We use a sparse regression model, with SNPs grouped into pathways, to identify causal pathways associated with a quantitative trait. Notable features of our "pathways group lasso with adaptive weights" (P-GLAW) algorithm include the incorporation of all pathways in a single regression model, an adaptive pathway weighting procedure that accounts for factors biasing pathway selection, and the use of a bootstrap sampling procedure for the ranking of important pathways. P-GLAW takes account of the presence of overlapping pathways and uses a novel combination of techniques to optimise model estimation, making it fast to run, even on whole genome datasets. In a comparison study with an alternative pathways method based on univariate SNP statistics, our method demonstrates high sensitivity and specificity for the detection of important pathways, showing the greatest relative gains in performance where marginal SNP effect sizes are small.

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