Resampling-based inferences for compositional regression with application to beef cattle microbiomes

Abstract

Gut microbiomes are increasingly found to be associated with many health-related characteristics of humans as well as animals. Regression with compositional microbiomes covariates is commonly used to identify important bacterial taxa that are related to various phenotype responses. Often the dimension of microbiome taxa easily exceeds the number of available samples, which creates a serious challenge in the estimation and inference of the model. The sparse log-contrast regression method is useful for such cases as it can yield a model estimate that depends on only a small number of taxa. However, a formal statistical inference procedure for individual regression coefficients has not been properly established yet. We propose a new estimation and inference procedure for linear regression models with extremely low-sample-sized compositional predictors. Under the compositional log-contrast regression framework, the proposed approach consists of two steps. The first step is to screen relevant predictors by fitting a log-contrast model with a sparse penalty. The screened-in variables are used as predictors in the non-sparse log-contrast model in the second step, where each of the regression coefficients is tested using nonparametric, resampling-based methods such as permutation and bootstrap. The performances of the proposed methods are evaluated by a simulation study, which shows they outperform traditional approaches based on normal assumptions or large sample asymptotics. Application to steer microbiome data successfully identifies key bacterial taxa that are related to important cattle quality measures.