Joint Multiple Testing Procedures for Graphical Model Selection with Applications to Biological Networks

Gaussian graphical models have become popular tools for identifying relationships between genes when analyzing microarray expression data. In the classical undirected Gaussian graphical model setting, conditional independence relationships can be inferred from partial correlations obtained from the concentration matrix (= inverse covariance matrix) when the sample size n exceeds the number of parameters p which need to estimated. In situations where n \u3c p, another approach to graphical model estimation may rely on calculating unconditional (zero-order) and first-order partial correlations. In these settings, the goal is to identify a lower-order conditional independence graph, sometimes referred to as a ‘0-1 graphs’. For either choice of graph, model selection may involve a multiple testing problem, in which edges in a graph are drawn only after rejecting hypotheses involving (saturated or lower-order) partial correlation parameters. Most multiple testing procedures applied in previously proposed graphical model selection algorithms rely on standard, marginal testing methods which do not take into account the joint distribution of the test statistics derived from (partial) correlations. We propose and implement a multiple testing framework useful when testing for edge inclusion during graphical model selection. Two features of our methodology include (i) a computationally efficient and asymptotically valid test statistics joint null distribution derived from influence curves for correlation-based parameters, and (ii) the application of empirical Bayes joint multiple testing procedures which can effectively control a variety of popular Type I error rates by incorpo- rating joint null distributions such as those described here (Dudoit and van der Laan, 2008). Using a dataset from Arabidopsis thaliana, we observe that the use of more sophisticated, modular approaches to multiple testing allows one to identify greater numbers of edges when approximating an undirected graphical model using a 0-1 graph. Our framework may also be extended to edge testing algorithms for other types of graphical models (e.g., for classical undirected, bidirected, and directed acyclic graphs)

Active Learning for Undirected Graphical Model Selection

This paper studies graphical model selection, i.e., the problem of estimating a graph of statistical relationships among a collection of random variables. Conventional graphical model selection algorithms are passive, i.e., they require all the measurements to have been collected before processing begins. We propose an active learning algorithm that uses junction tree representations to adapt future measurements based on the information gathered from prior measurements. We prove that, under certain conditions, our active learning algorithm requires fewer scalar measurements than any passive algorithm to reliably estimate a graph. A range of numerical results validate our theory and demonstrates the benefits of active learning.Comment: AISTATS 201

Graphical Markov models, unifying results and their interpretation

Graphical Markov models combine conditional independence constraints with graphical representations of stepwise data generating processes.The models started to be formulated about 40 years ago and vigorous development is ongoing. Longitudinal observational studies as well as intervention studies are best modeled via a subclass called regression graph models and, especially traceable regressions. Regression graphs include two types of undirected graph and directed acyclic graphs in ordered sequences of joint responses. Response components may correspond to discrete or continuous random variables and may depend exclusively on variables which have been generated earlier. These aspects are essential when causal hypothesis are the motivation for the planning of empirical studies. To turn the graphs into useful tools for tracing developmental pathways and for predicting structure in alternative models, the generated distributions have to mimic some properties of joint Gaussian distributions. Here, relevant results concerning these aspects are spelled out and illustrated by examples. With regression graph models, it becomes feasible, for the first time, to derive structural effects of (1) ignoring some of the variables, of (2) selecting subpopulations via fixed levels of some other variables or of (3) changing the order in which the variables might get generated. Thus, the most important future applications of these models will aim at the best possible integration of knowledge from related studies.Comment: 34 Pages, 11 figures, 1 tabl

Maximum Likelihood Estimation in Gaussian Chain Graph Models under the Alternative Markov Property

The AMP Markov property is a recently proposed alternative Markov property for chain graphs. In the case of continuous variables with a joint multivariate Gaussian distribution, it is the AMP rather than the earlier introduced LWF Markov property that is coherent with data-generation by natural block-recursive regressions. In this paper, we show that maximum likelihood estimates in Gaussian AMP chain graph models can be obtained by combining generalized least squares and iterative proportional fitting to an iterative algorithm. In an appendix, we give useful convergence results for iterative partial maximization algorithms that apply in particular to the described algorithm.Comment: 15 pages, article will appear in Scandinavian Journal of Statistic