Adaptive and powerful microbiome multivariate association analysis via feature selection

The important role of human microbiome is being increasingly recognized in health and disease conditions. Since microbiome data is typically high dimensional, one popular mode of statistical association analysis for microbiome data is to pool individual microbial features into a group, and then conduct group-based multivariate association analysis. A corresponding challenge within this approach is to achieve adequate power to detect an association signal between a group of microbial features and the outcome of interest across a wide range of scenarios. Recognizing some existing methods’ susceptibility to the adverse effects of noise accumulation, we introduce the Adaptive Microbiome Association Test (AMAT), a novel and powerful tool for multivariate microbiome association analysis, which unifies both blessings of feature selection in high-dimensional inference and robustness of adaptive statistical association testing. AMAT first alleviates the burden of noise accumulation via distance correlation learning, and then conducts a data-adaptive association test under the flexible generalized linear model framework. Extensive simulation studies and real data applications demonstrate that AMAT is highly robust and often more powerful than several existing methods, while preserving the correct type I error rate. A free implementation of AMAT in R computing environment is available at https://github.com/kzb193/AMAT.