A novel graph theoretical approach for modeling microbiomes and inferring microbial ecological relationships

BACKGROUND: Microbiomes play vital roles in shaping environments and stabilize them based on their compositions and inter-species relationships among its species. Variations in microbial properties have been reported to have significant impact on their host environment. For example, variants in gut microbiomes have been reported to be associated with several chronic conditions, such as inflammatory disease and irritable bowel syndrome. However, how microbial bacteria contribute to pathogenesis still remains unclear and major research questions in this domain remain unanswered. METHODS: We propose a split graph model to represent the composition and interactions of a given microbiome. We used metagenomes from Korean populations in this study. The dataset consists of three different types of samples, viz. mucosal tissue and stool from Crohn’s disease patients and stool from healthy individuals. We use the split graph model to analyze the impact of microbial compositions on various host phenotypes. Utilizing the graph model, we have developed a pipeline that integrates genomic information and pathway analysis to characterize both critical informative components of inter-bacterial correlations and associations between bacterial taxa and various metabolic pathways. RESULTS: The obtained results highlight the importance of the microbial communities and their inter-relationships and show how these microbial structures are correlated with Crohn’s disease. We show that there are significant positive associations between detected taxonomic biomarkers as well as multiple functional modules in the split graph of mucosal tissue samples from CD patients. Bacteria Moraxellaceae and Pseudomonadaceae were detected as taxonomic biomarkers in CD groups. Higher abundance of these bacteria have been reported in previous study and several metabolic pathways associated with these bacteria were characterized in CD samples. CONCLUSIONS: The proposed pipeline provides a new way to approach the analysis of complex microbiomes. The results obtained from this study show great potential in unraveling mechansims in complex biological systems to understand how various components in such complex environments are associated with critical biological functions.