Efficient inference for genetic association studies with multiple outcomes

Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modelling are either too simplistic to be powerful or are impracticable for computational reasons. Inspired by Richardson et al. (2010, Bayesian Statistics 9), we consider a sparse multivariate regression model that allows simultaneous selection of predictors and associated responses. As Markov chain Monte Carlo (MCMC) inference on such models can be prohibitively slow when the number of genetic variants exceeds a few thousand, we propose a variational inference approach which produces posterior information very close to that of MCMC inference, at a much reduced computational cost. Extensive numerical experiments show that our approach outperforms popular variable selection methods and tailored Bayesian procedures, dealing within hours with problems involving hundreds of thousands of genetic variants and tens to hundreds of clinical or molecular outcomes

An Empirical Study of Stochastic Variational Algorithms for the Beta Bernoulli Process

Stochastic variational inference (SVI) is emerging as the most promising candidate for scaling inference in Bayesian probabilistic models to large datasets. However, the performance of these methods has been assessed primarily in the context of Bayesian topic models, particularly latent Dirichlet allocation (LDA). Deriving several new algorithms, and using synthetic, image and genomic datasets, we investigate whether the understanding gleaned from LDA applies in the setting of sparse latent factor models, specifically beta process factor analysis (BPFA). We demonstrate that the big picture is consistent: using Gibbs sampling within SVI to maintain certain posterior dependencies is extremely effective. However, we find that different posterior dependencies are important in BPFA relative to LDA. Particularly, approximations able to model intra-local variable dependence perform best.Comment: ICML, 12 pages. Volume 37: Proceedings of The 32nd International Conference on Machine Learning, 201

Binary Linear Classification and Feature Selection via Generalized Approximate Message Passing

For the problem of binary linear classification and feature selection, we propose algorithmic approaches to classifier design based on the generalized approximate message passing (GAMP) algorithm, recently proposed in the context of compressive sensing. We are particularly motivated by problems where the number of features greatly exceeds the number of training examples, but where only a few features suffice for accurate classification. We show that sum-product GAMP can be used to (approximately) minimize the classification error rate and max-sum GAMP can be used to minimize a wide variety of regularized loss functions. Furthermore, we describe an expectation-maximization (EM)-based scheme to learn the associated model parameters online, as an alternative to cross-validation, and we show that GAMP's state-evolution framework can be used to accurately predict the misclassification rate. Finally, we present a detailed numerical study to confirm the accuracy, speed, and flexibility afforded by our GAMP-based approaches to binary linear classification and feature selection