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Joint Estimation of Multiple Dependent Gaussian Graphical Models with Applications to Mouse Genomics.

ABSTRACT: Gaussian graphical models are widely used to represent conditional dependence among random variables. In this paper, we propose a novel estimator for data arising from a group of Gaussian graphical models that are themselves dependent. A motivating example is that of modeling gene expression collected on multiple tissues from the same individual: here the multivariate outcome is affected by dependencies acting not only at the level of the specific tissues, but also at the level of the whole body; existing methods that assume independence among graphs are not applicable in this case. To estimate multiple dependent graphs, we decompose the problem into two graphical layers: the systemic layer, which affects all outcomes and thereby induces cross-graph dependence, and the category-specific layer, which represents graph-specific variation. We propose a graphical EM technique that estimates both layers jointly, establish estimation consistency and selection sparsistency of the proposed estimator, and confirm by simulation that the EM method is superior to a simple one-step method. We apply our technique to mouse genomics data and obtain biologically plausible results.

SUBMITTER: Xie Y

PROVIDER: S-EPMC5640885 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Joint Estimation of Multiple Dependent Gaussian Graphical Models with Applications to Mouse Genomics.

Xie Yuying Y Liu Yufeng Y Valdar William W

Biometrika 20160901 3

Gaussian graphical models are widely used to represent conditional dependence among random variables. In this paper, we propose a novel estimator for data arising from a group of Gaussian graphical models that are themselves dependent. A motivating example is that of modeling gene expression collected on multiple tissues from the same individual: here the multivariate outcome is affected by dependencies acting not only at the level of the specific tissues, but also at the level of the whole body ...[more]

PMID: 29038606

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Project description:BackgroundGraphical Gaussian models are popular tools for the estimation of (undirected) gene association networks from microarray data. A key issue when the number of variables greatly exceeds the number of samples is the estimation of the matrix of partial correlations. Since the (Moore-Penrose) inverse of the sample covariance matrix leads to poor estimates in this scenario, standard methods are inappropriate and adequate regularization techniques are needed. Popular approaches include biased estimates of the covariance matrix and high-dimensional regression schemes, such as the Lasso and Partial Least Squares.ResultsIn this article, we investigate a general framework for combining regularized regression methods with the estimation of Graphical Gaussian models. This framework includes various existing methods as well as two new approaches based on ridge regression and adaptive lasso, respectively. These methods are extensively compared both qualitatively and quantitatively within a simulation study and through an application to six diverse real data sets. In addition, all proposed algorithms are implemented in the R package "parcor", available from the R repository CRAN.ConclusionIn our simulation studies, the investigated non-sparse regression methods, i.e. Ridge Regression and Partial Least Squares, exhibit rather conservative behavior when combined with (local) false discovery rate multiple testing in order to decide whether or not an edge is present in the network. For networks with higher densities, the difference in performance of the methods decreases. For sparse networks, we confirm the Lasso's well known tendency towards selecting too many edges, whereas the two-stage adaptive Lasso is an interesting alternative that provides sparser solutions. In our simulations, both sparse and non-sparse methods are able to reconstruct networks with cluster structures. On six real data sets, we also clearly distinguish the results obtained using the non-sparse methods and those obtained using the sparse methods where specification of the regularization parameter automatically means model selection. In five out of six data sets, Partial Least Squares selects very dense networks. Furthermore, for data that violate the assumption of uncorrelated observations (due to replications), the Lasso and the adaptive Lasso yield very complex structures, indicating that they might not be suited under these conditions. The shrinkage approach is more stable than the regression based approaches when using subsampling.

Dataset Information

Joint Estimation of Multiple Dependent Gaussian Graphical Models with Applications to Mouse Genomics.

Publications

Joint Estimation of Multiple Dependent Gaussian Graphical Models with Applications to Mouse Genomics.

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