System Biology Modeling with Compositional Microbiome Data Reveals Personalized Gut Microbial Dynamics and Keystone Species

Abstract

A growing body of literature points to the important roles that different microbial communities play in diverse natural environments and the human body. The dynamics of these communities is driven by a range of microbial interactions from symbiosis to predatorprey relationships, the majority of which are poorly understood, making it hard to predict the response of the community to different perturbations. With the increasing availability of high-throughput sequencing based community composition data, it is now conceivable to directly learn models that explicitly define microbial interactions and explain community dynamics. The applicability of these approaches is however affected by several experimental limitations, particularly the compositional nature of sequencing data. We present a new computational approach (BEEM) that addresses this key limitation in the inference of generalised Lotka-Volterra models (gLVMs) by coupling biomass estimation and model inference in an expectation maximization like algorithm (BEEM). Surprisingly, BEEM outperforms state-of-the-art methods for inferring gLVMs, while simultaneously eliminating the need for additional experimental biomass data as input. BEEM's application to previously inaccessible public datasets (due to the lack of biomass data) allowed us for the first time to analyse microbial communities in the human gut on a per individual basis, revealing personalised dynamics and keystone species.