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International journal of systems and synthetic biology最新文献

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A Bayesian Approach for Graph-constrained Estimation for High-dimensional Regression. 高维回归图约束估计的贝叶斯方法。
Hokeun Sun, Hongzhe Li

Many different biological processes are represented by network graphs such as regulatory networks, metabolic pathways, and protein-protein interaction networks. Since genes that are linked on the networks usually have biologically similar functions, the linked genes form molecular modules to affect the clinical phenotypes/outcomes. Similarly, in large-scale genetic association studies, many SNPs are in high linkage disequilibrium (LD), which can also be summarized as a LD graph. In order to incorporate the graph information into regression analysis with high dimensional genomic data as predictors, we introduce a Bayesian approach for graph-constrained estimation (Bayesian GRACE) and regularization, which controls the amount of regularization for sparsity and smoothness of the regression coefficients. The Bayesian estimation with their posterior distributions can provide credible intervals for the estimates of the regression coefficients along with standard errors. The deviance information criterion (DIC) is applied for model assessment and tuning parameter selection. The performance of the proposed Bayesian approach is evaluated through simulation studies and is compared with Bayesian Lasso and Bayesian Elastic-net procedures. We demonstrate our method in an analysis of data from a case-control genome-wide association study of neuroblastoma using a weighted LD graph.

许多不同的生物过程由网络图表示,如调节网络、代谢途径和蛋白质-蛋白质相互作用网络。由于连接在网络上的基因通常具有生物学上相似的功能,因此连接的基因形成分子模块来影响临床表型/结果。同样,在大规模的遗传关联研究中,许多snp处于高连锁不平衡(LD)状态,也可以用LD图来概括。为了将图信息整合到以高维基因组数据作为预测因子的回归分析中,我们引入了一种用于图约束估计(贝叶斯GRACE)和正则化的贝叶斯方法,该方法控制了回归系数的稀疏性和平滑性的正则化量。贝叶斯估计及其后验分布可以为回归系数的估计和标准误差提供可信区间。应用偏差信息准则(DIC)进行模型评估和参数选择。通过仿真研究评估了所提出的贝叶斯方法的性能,并与贝叶斯Lasso和贝叶斯Elastic-net方法进行了比较。我们使用加权LD图对神经母细胞瘤病例对照全基因组关联研究的数据进行分析,证明了我们的方法。
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International journal of systems and synthetic biology
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