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FastGGM: An Efficient Algorithm for the Inference of Gaussian Graphical Model in Biological Networks

机译:FastGGM:生物网络中高斯图形模型推理的高效算法

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摘要

Biological networks provide additional information for the analysis of human diseases, beyond the traditional analysis that focuses on single variables. Gaussian graphical model (GGM), a probability model that characterizes the conditional dependence structure of a set of random variables by a graph, has wide applications in the analysis of biological networks, such as inferring interaction or comparing differential networks. However, existing approaches are either not statistically rigorous or are inefficient for high-dimensional data that include tens of thousands of variables for making inference. In this study, we propose an efficient algorithm to implement the estimation of GGM and obtain p-value and confidence interval for each edge in the graph, based on a recent proposal by Ren et al., 2015. Through simulation studies, we demonstrate that the algorithm is faster by several orders of magnitude than the current implemented algorithm for Ren et al. without losing any accuracy. Then, we apply our algorithm to two real data sets: transcriptomic data from a study of childhood asthma and proteomic data from a study of Alzheimer’s disease. We estimate the global gene or protein interaction networks for the disease and healthy samples. The resulting networks reveal interesting interactions and the differential networks between cases and controls show functional relevance to the diseases. In conclusion, we provide a computationally fast algorithm to implement a statistically sound procedure for constructing Gaussian graphical model and making inference with high-dimensional biological data. The algorithm has been implemented in an R package named “FastGGM”.
机译:除了专注于单个变量的传统分析之外,生物网络还提供了用于分析人类疾病的其他信息。高斯图形模型(GGM)是一种概率模型,它通过图形来描述一组随机变量的条件依存结构,在生物网络分析中具有广泛的应用,例如推断相互作用或比较差分网络。但是,现有的方法在统计上并不严格,或者对于包含数以万计的变量进行推断的高维数据而言效率不高。在这项研究中,我们根据Ren等人(2015年)的最新建议,提出了一种有效的算法,可用于估算GGM并获得图中每个边缘的p值和置信区间。通过仿真研究,我们证明了该算法比Ren等人当前实现的算法快几个数量级。而不会失去任何准确性。然后,我们将算法应用于两个真实的数据集:儿童哮喘研究的转录组数据和阿尔茨海默氏病研究的蛋白质组数据。我们估计该疾病和健康样本的全球基因或蛋白质相互作用网络。由此产生的网络揭示出有趣的相互作用,而病例与对照之间的差异网络则显示出与疾病的功能相关性。总之,我们提供了一种计算速度快的算法,以实现统计上合理的过程,以构建高斯图形模型并推断高维生物学数据。该算法已在名为“ FastGGM”的R包中实现。

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