Inference of Environmental Factor-Microbe and Microbe-Microbe Associations from Metagenomic Data Using a Hierarchical...

The inference of associations between environmental factors and microbes and among microbes is critical to interpreting metagenomic data, but compositional bias, indirect associations resulting from common factors, and variance within metagenomic sequencing data limit the discovery of associations. To account for these problems, we propose metagenomic Lognormal-Dirichlet-Multinomial (mLDM), a hierarchical Bayesian model with sparsity constraints, to estimate absolute microbial abundance and simultaneously infer both conditionally dependent associations among microbes and direct associations between microbes and environmental factors. We empirically show the effectiveness of the mLDM model using synthetic data, data from the TARA Oceans project, and a colorectal cancer dataset. Finally, we apply mLDM to 16S sequencing data from the western English Channel and report several associations. Our model can be used on both natural environmental and human metagenomic datasets, promoting the understanding of associations in the microbial community.