pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.

Abstract

The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce. We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets. The R package pldist is available on GitHub at https://github.com/aplantin/pldist. Supplementary data are available at Bioinformatics online.