Learning Microbial Interaction Networks from Metagenomic Count Data
Many microbes associate with higher eukaryotes and impact their vitality. In order to engineer microbiomes for host benefit, we must understand the rules of community assembly and maintenence, which in large part, demands an understanding of the direct interactions between community members. Toward this end, we’ve developed a Poisson-multivariate normal hierarchical model to learn direct interactions from the count-based output of standard metagenomics sequencing experiments. Our model controls for confounding predictors at the Poisson layer, and captures direct taxon-taxon interactions at the multivariate normal layer using an \(\ell _1\) penalized precision matrix. We show in a synthetic experiment that our method handily outperforms state-of-the-art methods such as SparCC and the graphical lasso (glasso). In a real, in planta perturbation experiment of a nine member bacterial community, we show our model, but not SparCC or glasso, correctly resolves a direct interaction structure among three community members that associate with Arabidopsis thaliana roots. We conclude that our method provides a structured, accurate, and distributionally reasonable way of modeling correlated count based random variables and capturing direct interactions among them.
Code Availability: Our model is available on CRAN as an R package, MInt.
KeywordsMetagenomics Hierarchical model \(\ell _1\)-penalty Precision matrix Conditional independence
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- 1.Human Microbiome Project Consortium. The Structure, function and diversity ofthe healthy human microbiome. Nature 486(7402), 207–14 (2012)Google Scholar
- 2.Lundberg, D.S., Lebeis, S.L., Paredes, S.H., Yourstone, S., Gehring, J., Malfatti, S., Tremblay, J., Engelbrektson, A., Kunin, V., Del Rio, T.G., Edgar, R.C., Eickhorst, T., Ley, R.E., Hugenholtz, P., Tringe, S.G., Dangl, J.L.: Defining the core Arabidopsis thaliana root microbiome. Nature 488(7409), 86–90 (2012)CrossRefGoogle Scholar
- 4.Segata, N., Boernigen, D., Tickle, T.L., Morgan, X.C., Garrett, W.S., Huttenhower, C.: Computational meta’omics for microbial community studies. Molecular Systems Biology 9(666), 666 (2013)Google Scholar