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

Fast Exact Bayesian Inference for Sparse Signals in the Normal Sequence Model

We consider exact algorithms for Bayesian inference with model selection priors (including spike-and-slab priors) in the sparse normal sequence model. Because the best existing exact algorithm becomes numerically unstable for sample sizes over n=500, there has been much attention for alternative approaches like approximate algorithms (Gibbs sampling, variational Bayes, etc.), shrinkage priors (e.g. the Horseshoe prior and the Spike-and-Slab LASSO) or empirical Bayesian methods. However, by introducing algorithmic ideas from online sequential prediction, we show that exact calculations are feasible for much larger sample sizes: for general model selection priors we reach n=25000, and for certain spike-and-slab priors we can easily reach n=100000. We further prove a de Finetti-like result for finite sample sizes that characterizes exactly which model selection priors can be expressed as spike-and-slab priors. The computational speed and numerical accuracy of the proposed methods are demonstrated in experiments on simulated data, on a differential gene expression data set, and to compare the effect of multiple hyper-parameter settings in the beta-binomial prior. In our experimental evaluation we compute guaranteed bounds on the numerical accuracy of all new algorithms, which shows that the proposed methods are numerically reliable whereas an alternative based on long division is not

Variational Dropout and the Local Reparameterization Trick

We investigate a local reparameterizaton technique for greatly reducing the variance of stochastic gradients for variational Bayesian inference (SGVB) of a posterior over model parameters, while retaining parallelizability. This local reparameterization translates uncertainty about global parameters into local noise that is independent across datapoints in the minibatch. Such parameterizations can be trivially parallelized and have variance that is inversely proportional to the minibatch size, generally leading to much faster convergence. Additionally, we explore a connection with dropout: Gaussian dropout objectives correspond to SGVB with local reparameterization, a scale-invariant prior and proportionally fixed posterior variance. Our method allows inference of more flexibly parameterized posteriors; specifically, we propose variational dropout, a generalization of Gaussian dropout where the dropout rates are learned, often leading to better models. The method is demonstrated through several experiments