Testing for Differences in Gaussian Graphical Models: Applications to Brain Connectivity

Functional brain networks are well described and estimated from data with Gaussian Graphical Models (GGMs), e.g. using sparse inverse covariance estimators. Comparing functional connectivity of subjects in two populations calls for comparing these estimated GGMs. Our goal is to identify differences in GGMs known to have similar structure. We characterize the uncertainty of differences with confidence intervals obtained using a parametric distribution on parameters of a sparse estimator. Sparse penalties enable statistical guarantees and interpretable models even in high-dimensional and low-sample settings. Characterizing the distributions of sparse models is inherently challenging as the penalties produce a biased estimator. Recent work invokes the sparsity assumptions to effectively remove the bias from a sparse estimator such as the lasso. These distributions can be used to give confidence intervals on edges in GGMs, and by extension their differences. However, in the case of comparing GGMs, these estimators do not make use of any assumed joint structure among the GGMs. Inspired by priors from brain functional connectivity we derive the distribution of parameter differences under a joint penalty when parameters are known to be sparse in the difference. This leads us to introduce the debiased multi-task fused lasso, whose distribution can be characterized in an efficient manner. We then show how the debiased lasso and multi-task fused lasso can be used to obtain confidence intervals on edge differences in GGMs. We validate the techniques proposed on a set of synthetic examples as well as neuro-imaging dataset created for the study of autism

Tree-guided group lasso for multi-response regression with structured sparsity, with an application to eQTL mapping

We consider the problem of estimating a sparse multi-response regression function, with an application to expression quantitative trait locus (eQTL) mapping, where the goal is to discover genetic variations that influence gene-expression levels. In particular, we investigate a shrinkage technique capable of capturing a given hierarchical structure over the responses, such as a hierarchical clustering tree with leaf nodes for responses and internal nodes for clusters of related responses at multiple granularity, and we seek to leverage this structure to recover covariates relevant to each hierarchically-defined cluster of responses. We propose a tree-guided group lasso, or tree lasso, for estimating such structured sparsity under multi-response regression by employing a novel penalty function constructed from the tree. We describe a systematic weighting scheme for the overlapping groups in the tree-penalty such that each regression coefficient is penalized in a balanced manner despite the inhomogeneous multiplicity of group memberships of the regression coefficients due to overlaps among groups. For efficient optimization, we employ a smoothing proximal gradient method that was originally developed for a general class of structured-sparsity-inducing penalties. Using simulated and yeast data sets, we demonstrate that our method shows a superior performance in terms of both prediction errors and recovery of true sparsity patterns, compared to other methods for learning a multivariate-response regression.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS549 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Oracle Inequalities and Optimal Inference under Group Sparsity

We consider the problem of estimating a sparse linear regression vector $\beta^*$ under a gaussian noise model, for the purpose of both prediction and model selection. We assume that prior knowledge is available on the sparsity pattern, namely the set of variables is partitioned into prescribed groups, only few of which are relevant in the estimation process. This group sparsity assumption suggests us to consider the Group Lasso method as a means to estimate $\beta^*$. We establish oracle inequalities for the prediction and $\ell_2$ estimation errors of this estimator. These bounds hold under a restricted eigenvalue condition on the design matrix. Under a stronger coherence condition, we derive bounds for the estimation error for mixed $(2,p)$-norms with $1\le p\leq \infty$. When $p=\infty$, this result implies that a threshold version of the Group Lasso estimator selects the sparsity pattern of $\beta^*$ with high probability. Next, we prove that the rate of convergence of our upper bounds is optimal in a minimax sense, up to a logarithmic factor, for all estimators over a class of group sparse vectors. Furthermore, we establish lower bounds for the prediction and $\ell_2$ estimation errors of the usual Lasso estimator. Using this result, we demonstrate that the Group Lasso can achieve an improvement in the prediction and estimation properties as compared to the Lasso.Comment: 37 page