Explainable Machine Learning for Longitudinal Multi-Omic Microbiome

Abstract

Over the years, research studies have shown there is a key connection between the microbial community in the gut, genes, and immune system. Understanding this association may help discover the cause of complex chronic idiopathic disorders such as inflammatory bowel disease. Even though important efforts have been put into the field, the functions, dynamics, and causation of dysbiosis state performed by the microbial community remains unclear. Machine learning models can help elucidate important connections and relationships between microbes in the human host. Our study aims to extend the current knowledge of associations between the human microbiome and health and disease through the application of dynamic Bayesian networks to describe the temporal variation of the gut microbiota and dynamic relationships between taxonomic entities and clinical variables. We develop a set of preprocessing steps to clean, filter, select, integrate, and model informative metagenomics, metatranscriptomics, and metabolomics longitudinal data from the Human Microbiome Project. This study accomplishes novel network models with satisfactory predictive performance (accuracy = 0.648) for each inflammatory bowel disease state, validating Bayesian networks as a framework for developing interpretable models to help understand the basic ways the different biological entities (taxa, genes, metabolites) interact with each other in a given environment (human gut) over time. These findings can serve as a starting point to advance the discovery of novel therapeutic approaches and new biomarkers for precision medicine.