We discuss the theoretical structure and constructive methodology for large-scale graphical models, motivated by their potential in evaluating and aiding the exploration of patterns of association in gene expression data. The theoretical discussion covers basic ideas and connections between Gaussian graphical models, dependency networks and specific classes of directed acyclic graphs we refer to as compositional networks. We describe a constructive approach to generating interesting graphical models for very high-dimensional distributions that builds on the relationships between these various stylized graphical representations. Issues of consistency of models and priors across dimension are key. The resulting methods are of value in evaluating patterns of association in large-scale gene expression data with a view to generating biological insights about genes related to a known molecular pathway or set of specified genes. Some initial examples relate to the estrogen receptor pathway in breast cancer, and the Rb-E2F cell proliferation control pathway. r 2004 Elsevier Inc. All rights reserved.
The lasso estimate for linear regression corresponds to a posterior mode when independent, double-exponential prior distributions are placed on the regression coefficients. This paper introduces new aspects of the broader Bayesian treatment of lasso regression. A direct characterization of the regression coefficients' posterior distribution is provided, and computation and inference under this characterization is shown to be straightforward. Emphasis is placed on point estimation using the posterior mean, which facilitates prediction of future observations via the posterior predictive distribution. It is shown that the standard lasso prediction method does not necessarily agree with model-based, Bayesian predictions. A new Gibbs sampler for Bayesian lasso regression is introduced.
While Bayesian analogues of lasso regression have become popular, comparatively little has been said about formal treatments of model uncertainty in such settings. This paper describes methods that can be used to evaluate the posterior distribution over the space of all possible regression models for Bayesian lasso regression. Access to the model space posterior distribution is necessary if modelaveraged inference-e.g., model-averaged prediction and calculation of posterior variable inclusion probabilities-is desired. The key element of all such inference is the ability to evaluate the marginal likelihood of the data under a given regression model, which has so far proved difficult for the Bayesian lasso. This paper describes how the marginal likelihood can be accurately computed when the number of predictors in the model is not too large, allowing for model space enumeration when the total number of possible predictors is modest. In cases where the total number of possible predictors is large, a simple Markov chain Monte Carlo approach for sampling the model space posterior is provided. This Gibbs sampling approach is similar in spirit to the stochastic search variable selection methods that have become one of the main tools for addressing Bayesian regression model uncertainty, and the adaption of these methods to the Bayesian lasso is shown to be straightforward.
In regression applications with categorical predictors, interest often focuses on comparing the null hypothesis of homogeneity to an ordered alternative. This article proposes a Bayesian approach for addressing this problem in the setting of normal linear and probit regression models. The regression coefficients are assigned a conditionally conjugate prior density consisting of mixtures of point masses at 0 and truncated normal densities, with a (possibly unknown) changepoint parameter included to accommodate umbrella ordering. Two strategies of prior elicitation are considered: (1) a Bayesian Bonferroni approach in which the probability of the global null hypothesis is specified and local hypotheses are considered independent; and (2) an approach which treats these probabilities as random. A single Gibbs sampling chain can be used to obtain posterior probabilities for the different hypotheses and to estimate regression coefficients and predictive quantities either by model averaging or under the preferred hypothesis. The methods are applied to data from a carcinogenesis study.
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