High-Dimensional Bayesian Semiparametric Models for Small Samples: A Principled Approach to the Analysis of Cytokine Expression Data

Abstract

In laboratory medicine, due to the lack of sample availability and resources, measurements of many quantities of interest are commonly collected over a few samples, making statistical inference particularly challenging. In this context, several hypotheses can be tested, and studies are not often powered accordingly. We present a semiparametric Bayesian approach to effectively test multiple hypotheses applied to an experiment that aims to identify cytokines involved in Crohn's disease (CD) infection that may be ongoing in multiple tissues. We assume that the positive correlation commonly observed between cytokines is caused by latent groups of effects, which in turn result from a common cause. These clusters are effectively modeled through a Dirichlet Process (DP) that is one of the most popular choices as nonparametric prior in Bayesian statistics and has been proven to be a powerful tool for model-based clustering. We use a spike–slab distribution as the base measure of the DP. The nonparametric part has been included in an additive model whose parametric component is a Bayesian hierarchical model. We include simulations that empirically demonstrate the effectiveness of the proposed testing procedure in settings that mimic our application's sample size and data structure. Our CD data analysis shows strong evidence of a cytokine gradient in the external intestinal tissue.