Solving the Empirical Bayes Normal Means Problem with Correlated Noise

arXiv.org Machine Learning

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.


Sequential Dirichlet Process Mixtures of Multivariate Skew t-distributions for Model-based Clustering of Flow Cytometry Data

arXiv.org Machine Learning

Flow cytometry is a high-throughput technology used to quantify multiple surface and intracellular markers at the level of a single cell. This enables to identify cell sub-types, and to determine their relative proportions. Improvements of this technology allow to describe millions of individual cells from a blood sample using multiple markers. This results in high-dimensional datasets, whose manual analysis is highly time-consuming and poorly reproducible. While several methods have been developed to perform automatic recognition of cell populations, most of them treat and analyze each sample independently. However, in practice, individual samples are rarely independent (e.g. longitudinal studies). Here, we propose to use a Bayesian nonparametric approach with Dirichlet process mixture (DPM) of multivariate skew $t$-distributions to perform model based clustering of flow-cytometry data. DPM models directly estimate the number of cell populations from the data, avoiding model selection issues, and skew $t$-distributions provides robustness to outliers and non-elliptical shape of cell populations. To accommodate repeated measurements, we propose a sequential strategy relying on a parametric approximation of the posterior. We illustrate the good performance of our method on simulated data, on an experimental benchmark dataset, and on new longitudinal data from the DALIA-1 trial which evaluates a therapeutic vaccine against HIV. On the benchmark dataset, the sequential strategy outperforms all other methods evaluated, and similarly, leads to improved performance on the DALIA-1 data. We have made the method available for the community in the R package NPflow.


Bayesian Inference of Spreading Processes on Networks

arXiv.org Machine Learning

Infectious diseases are studied to understand their spreading mechanisms, to evaluate control strategies and to predict the risk and course of future outbreaks. Because people only interact with a small number of individuals, and because the structure of these interactions matters for spreading processes, the pairwise relationships between individuals in a population can be usefully represented by a network. Although the underlying processes of transmission are different, the network approach can be used to study the spread of pathogens in a contact network or the spread of rumors in an online social network. We study simulated simple and complex epidemics on synthetic networks and on two empirical networks, a social / contact network in an Indian village and an online social network in the U.S. Our goal is to learn simultaneously about the spreading process parameters and the source node (first infected node) of the epidemic, given a fixed and known network structure, and observations about state of nodes at several points in time. Our inference scheme is based on approximate Bayesian computation (ABC), an inference technique for complex models with likelihood functions that are either expensive to evaluate or analytically intractable. ABC enables us to adopt a Bayesian approach to the problem despite the posterior distribution being very complex. Our method is agnostic about the topology of the network and the nature of the spreading process. It generally performs well and, somewhat counter-intuitively, the inference problem appears to be easier on more heterogeneous network topologies, which enhances its future applicability to real-world settings where few networks have homogeneous topologies.


A Bayesian Group Sparse Multi-Task Regression Model for Imaging Genetics

arXiv.org Machine Learning

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.


Segregated Graphs and Marginals of Chain Graph Models

Neural Information Processing Systems

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.