Identification and characterization of microbiome-derived biomarkers via novel and robust systems-based approaches.

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Research Goal & Scientific Approach: Microbiomes exist in many different environments and interact with most living species. Over the last decade, the level of interest and research on the microbiome has exploded. However, the rate at which data is being generated is outpacing researchers' current ability to identify robust microbial biomarkers in various environmental and host-associated conditions. Identifying microbial biomarkers from these large surveys is the first crucial step before being further studied to determine how they function and interact with other living organisms. Current methods for characterizing the relationship between types of microbes and their function are still limited and underdeveloped. Therefore, the main goal of this research program is to create a cohesive, visual framework that uses a combination of novel and existing bioinformatic approaches for the identification of new microbial biomarkers. Building upon recent research in our lab, our research program will focus on three main objectives. First, we propose a harmonized approach to characterize the microbial taxa and functions from metagenomic sequencing data by integrating two of the main approaches currently used. This integrated approach would provide the benefits of both techniques while minimizing their individual drawbacks. Second, we will explore and develop new ways to identify functions that are of biological interest in a community, while reducing noise due to technical variation. Third, we will create a novel graphical framework for biomarker discovery and visualization. This framework will include existing statistical and machine learning methods, along with the novel approaches developed in this research program. Unlike previous tools, this framework will focus on utilizing the taxonomic context of all microbial functions to improve the identification of robust biomarkers. These new approaches will be tested and validated using multiple datasets from various sources including environmental, host-associated, and human studies. Importance of Research & Anticipated Outcomes: Given the drastic increase in microbiome studies in the natural sciences and the interest in the discovery of microbial biomarkers from these types of studies, improvement to these approaches will have a profound affect across numerous research areas such as microbiology, genomics, and bioinformatics. In addition, the field of microbiome research requires skills and knowledge across many disciplines and as such training of highly qualified personnel (HQP) through this program will include cross disciplinary training in these diverse disciplines. These highly qualified personnel are in high demand in academic, government, and industry settings. The proposed research program will accelerate microbiome research in Canada and beyond, by tackling current bottlenecks in computational analysis and biomarker discovery from complex microbiome data.