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Understanding how microbes interact with each other is key to revealing the underlying role that microorganisms play in the host or environment and to identifying microorganisms as an agent that can potentially alter the host or environment. For example, understanding how the microbial interactions associate with parasitic infection can help resolve potential drug or diagnostic test for parasitic infection. To unravel the microbial interactions, existing tools often rely on graphical models to infer the conditional dependence of microbial abundances to represent their interactions. However, current methods do not simultaneously account for the discreteness, compositionality, and heterogeneity inherent to microbiome data. Thus, we build a new approach called “compositional graphical lasso” upon existing tools by incorporating the above characteristics into the graphical model explicitly. We illustrate the advantage of compositional graphical lasso over current methods under a variety of simulation scenarios and on a benchmark study, the  Tara  Oceans Project. Moreover, we present our results from the analysis of a dataset from the Zebrafish Parasite Infection Study, which aims to gain insight into how the gut microbiome and parasite burden covary during infection, thus, uncovering novel putative methods of disrupting parasite success. Our approach identifies changes in interaction degree between infected and uninfected individuals for three taxa,  Photobacterium ,  Gemmobacter , and  Paucibacter , which are inversely predicted by other methods. Further investigation of these method-specific taxa interaction changes reveals their biological plausibility. In particular, we speculate on the potential pathobiotic roles of  Photobacterium  and  Gemmobacter  in the zebrafish gut, and the potential probiotic role of  Paucibacter . Collectively, our analyses demonstrate that compositional graphical lasso provides a powerful means of accurately resolving interactions between microbiota and can thus drive novel biological discovery.  Supplementary materials  for this article are available online.

Compositional Graphical Lasso Resolves the Impact of Parasitic Infection on Gut Microbial Interaction Networks in a Zebrafish Model