The Normal Means problem plays a fundamental role in many areas of modern high-dimensional statistics, both in theory and practice. And the Empirical Bayes (EB) approach to solving this problem has been shown to be highly effective, again both in theory and practice. However, almost all EB treatments of the Normal Means problem assume that the observations are independent. In practice correlations are ubiquitous in real-world applications, and these correlations can grossly distort EB estimates. Here, exploiting theory from Schwartzman (2010), we develop new EB methods for solving the Normal Means problem that take account of unknown correlations among observations. We provide practical software implementations of these methods, and illustrate them in the context of large-scale multiple testing problems and False Discovery Rate (FDR) control. In realistic numerical experiments our methods compare favorably with other commonly-used multiple testing methods.

One of the most fundamental problems in causal inference is the estimation of a causal effect when variables are confounded. This is difficult in an observational study, because one has no direct evidence that all confounders have been adjusted for. We introduce a novel approach for estimating causal effects that exploits observational conditional independencies to suggest "weak" paths in a unknown causal graph. The widely used faithfulness condition of Spirtes et al. is relaxed to allow for varying degrees of "path cancellations" that imply conditional independencies but do not rule out the existence of confounding causal paths. The outcome is a posterior distribution over bounds on the average causal effect via a linear programming approach and Bayesian inference. We claim this approach should be used in regular practice along with other default tools in observational studies.

Greenlaw, Keelin, Szefer, Elena, Graham, Jinko, Lesperance, Mary, Nathoo, Farouk S.

Motivation: Recent advances in technology for brain imaging and high-throughput genotyping have motivated studies examining the influence of genetic variation on brain structure. Wang et al. (Bioinformatics, 2012) have developed an approach for the analysis of imaging genomic studies using penalized multi-task regression with regularization based on a novel group $l_{2,1}$-norm penalty which encourages structured sparsity at both the gene level and SNP level. While incorporating a number of useful features, the proposed method only furnishes a point estimate of the regression coefficients; techniques for conducting statistical inference are not provided. A new Bayesian method is proposed here to overcome this limitation. Results: We develop a Bayesian hierarchical modeling formulation where the posterior mode corresponds to the estimator proposed by Wang et al. (Bioinformatics, 2012), and an approach that allows for full posterior inference including the construction of interval estimates for the regression parameters. We show that the proposed hierarchical model can be expressed as a three-level Gaussian scale mixture and this representation facilitates the use of a Gibbs sampling algorithm for posterior simulation. Simulation studies demonstrate that the interval estimates obtained using our approach achieve adequate coverage probabilities that outperform those obtained from the nonparametric bootstrap. Our proposed methodology is applied to the analysis of neuroimaging and genetic data collected as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and this analysis of the ADNI cohort demonstrates clearly the value added of incorporating interval estimation beyond only point estimation when relating SNPs to brain imaging endophenotypes.

Normative expert systems have not become commonplace because they have been difficult to build and use. Over the past decade, however, researchers have developed the influence diagram, a graphical representation of a decision maker's beliefs, alternatives, and preferences that serves as the knowledge base of a normative expert system. Most people who have seen the representation find it intuitive and easy to use. Consequently, the influence diagram has overcome significantly the barriers to constructing normative expert systems. Nevertheless, building influence diagrams is not practical for extremely large and complex domains. In this book, I address the difficulties associated with the construction of the probabilistic portion of an influence diagram, called a knowledge map, belief network, or Bayesian network. I introduce two representations that facilitate the generation of large knowledge maps. In particular, I introduce the similarity network, a tool for building the network structure of a knowledge map, and the partition, a tool for assessing the probabilities associated with a knowledge map. I then use these representations to build Pathfinder, a large normative expert system for the diagnosis of lymph-node diseases (the domain contains over 60 diseases and over 100 disease findings). In an early version of the system, I encoded the knowledge of the expert using an erroneous assumption that all disease findings were independent, given each disease. When the expert and I attempted to build a more accurate knowledge map for the domain that would capture the dependencies among the disease findings, we failed. Using a similarity network, however, we built the knowledge-map structure for the entire domain in approximately 40 hours. Furthermore, the partition representation reduced the number of probability assessments required by the expert from 75,000 to 14,000.

Bayesian networks are a popular representation of asymmetric (for example causal) relationships between random variables. Markov random fields (MRFs) are a complementary model of symmetric relationships used in computer vision, spatial modeling, and social and gene expression networks. A chain graph model under the Lauritzen-Wermuth-Frydenberg interpretation (hereafter a chain graph model) generalizes both Bayesian networks and MRFs, and can represent asymmetric and symmetric relationships together.As in other graphical models, the set of marginals from distributions in a chain graph model induced by the presence of hidden variables forms a complex model. One recent approach to the study of marginal graphical models is to consider a well-behaved supermodel. Such a supermodel of marginals of Bayesian networks, defined only by conditional independences, and termed the ordinary Markov model, was studied at length in (Evans and Richardson, 2014).In this paper, we show that special mixed graphs which we call segregated graphs can be associated, via a Markov property, with supermodels of a marginal of chain graphs defined only by conditional independences. Special features of segregated graphs imply the existence of a very natural factorization for these supermodels, and imply many existing results on the chain graph model, and ordinary Markov model carry over. Our results suggest that segregated graphs define an analogue of the ordinary Markov model for marginals of chain graph models.