A variational neural Bayes framework for inference on intractable posterior distributions

Classic Bayesian methods with complex models are frequently infeasible due to an intractable likelihood. Simulation-based inference methods, such as Approximate Bayesian Computing (ABC), calculate posteriors without accessing a likelihood function by leveraging the fact that data can be quickly simulated from the model, but converge slowly and/or poorly in high-dimensional settings. In this paper, we propose a framework for Bayesian posterior estimation by mapping data to posteriors of parameters using a neural network trained on data simulated from the complex model. Posterior distributions of model parameters are efficiently obtained by feeding observed data into the trained neural network. We show theoretically that our posteriors converge to the true posteriors in Kullback-Leibler divergence. Our approach yields computationally efficient and theoretically justified uncertainty quantification, which is lacking in existing simulation-based neural network approaches. Comprehensive simulation studies highlight our method's robustness and accuracy.

A statistical framework for GWAS of high dimensional phenotypes using summary statistics, with application to metabolite GWAS

The recent explosion of genetic and high dimensional biobank and 'omic' data has provided researchers with the opportunity to investigate the shared genetic origin (pleiotropy) of hundreds to thousands of related phenotypes. However, existing methods for multi-phenotype genome-wide association studies (GWAS) do not model pleiotropy, are only applicable to a small number of phenotypes, or provide no way to perform inference. To add further complication, raw genetic and phenotype data are rarely observed, meaning analyses must be performed on GWAS summary statistics whose statistical properties in high dimensions are poorly understood. We therefore developed a novel model, theoretical framework, and set of methods to perform Bayesian inference in GWAS of high dimensional phenotypes using summary statistics that explicitly model pleiotropy, beget fast computation, and facilitate the use of biologically informed priors. We demonstrate the utility of our procedure by applying it to metabolite GWAS, where we develop new nonparametric priors for genetic effects on metabolite levels that use known metabolic pathway information and foster interpretable inference at the pathway level.

Transfer Learning with Uncertainty Quantification: Random Effect Calibration of Source to Target (RECaST)

Transfer learning uses a data model, trained to make predictions or inferences on data from one population, to make reliable predictions or inferences on data from another population. Most existing transfer learning approaches are based on fine-tuning pre-trained neural network models, and fail to provide crucial uncertainty quantification. We develop a statistical framework for model predictions based on transfer learning, called RECaST. The primary mechanism is a Cauchy random effect that recalibrates a source model to a target population; we mathematically and empirically demonstrate the validity of our RECaST approach for transfer learning between linear models, in the sense that prediction sets will achieve their nominal stated coverage, and we numerically illustrate the method's robustness to asymptotic approximations for nonlinear models. Whereas many existing techniques are built on particular source models, RECaST is agnostic to the choice of source model. For example, our RECaST transfer learning approach can be applied to a continuous or discrete data model with linear or logistic regression, deep neural network architectures, etc. Furthermore, RECaST provides uncertainty quantification for predictions, which is mostly absent in the literature. We examine our method's performance in a simulation study and in an application to real hospital data.