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Fast Bayesian inference in large Gaussian graphical models.

ABSTRACT: Despite major methodological developments, Bayesian inference in Gaussian graphical models remains challenging in high dimension due to the tremendous size of the model space. This article proposes a method to infer the marginal and conditional independence structures between variables by multiple testing, which bypasses the exploration of the model space. Specifically, we introduce closed-form Bayes factors under the Gaussian conjugate model to evaluate the null hypotheses of marginal and conditional independence between variables. Their computation for all pairs of variables is shown to be extremely efficient, thereby allowing us to address large problems with thousands of nodes as required by modern applications. Moreover, we derive exact tail probabilities from the null distributions of the Bayes factors. These allow the use of any multiplicity correction procedure to control error rates for incorrect edge inclusion. We demonstrate the proposed approach on various simulated examples as well as on a large gene expression data set from The Cancer Genome Atlas.

SUBMITTER: Leday GGR

PROVIDER: S-EPMC6916355 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Fast Bayesian inference in large Gaussian graphical models.

Leday Gwenaël G R GGR Richardson Sylvia S

Biometrics 20190506 4

Despite major methodological developments, Bayesian inference in Gaussian graphical models remains challenging in high dimension due to the tremendous size of the model space. This article proposes a method to infer the marginal and conditional independence structures between variables by multiple testing, which bypasses the exploration of the model space. Specifically, we introduce closed-form Bayes factors under the Gaussian conjugate model to evaluate the null hypotheses of marginal and condi ...[more]

PMID: 31009060

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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

Fast Bayesian inference in large Gaussian graphical models.

Publications

Fast Bayesian inference in large Gaussian graphical models.

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