Analysis of compositions of microbiomes with bias correction.

Differential abundance (DA) analysis of microbiome data continues to be a challenging problem due to the complexity of the data. In this article we define the notion of “sampling fraction” and demonstrate a major hurdle in performing DA analysis of microbiome data is the bias introduced by differences in the sampling fractions across samples. We introduce a methodology called Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC), which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples. The absolute abundance data are modeled using a linear regression framework. This formulation makes a fundamental advancement in the field because, unlike the existing methods, it (a) provides statistically valid test with appropriate p-values, (b) provides confidence intervals for differential abundance of each taxon, (c) controls the False Discovery Rate (FDR), (d) maintains adequate power, and (e) is computationally simple to implement. Differential abundance analysis of microbiome data continues to be challenging due to data complexity. The authors propose a method which estimates the unknown sampling fractions and corrects the bias induced by their differences among samples.