High-Resolution Microbial 'Omics at Scale to Illuminate Enigmatic and Rather Picky Microbial Residents of the Human Oral Cavity

Microbes are the most common form of life on Earth and play a crucial role in biogeochemical processes that sustain all forms of life. Similar to every other habitat on Earth, microbes occupy almost every part of the human body and play an important role in health and disease. Our understanding of the ecology and evolution of microbes has been significantly changed due to the recent revolution in DNA sequencing technology and the rise of ‘omics data, which has transformed microbiology to a data-rich science. But new challenges are arising as computational tools and training that enable effective utilization of ‘omics data are lacking. Here I present my efforts to solve bottlenecks in the analysis of microbial ‘omics, and to empower microbiologists engaged in ‘omics data science. My work in developing computational tools has been driven by specific questions in microbial ecology. By utilizing high resolution ‘omics analysis approaches, I illuminated the evolutionary journey of cryptic microbial residents of the human oral cavity, with a focus on members of the candidate division TM7. My analysis revealed that TM7s split into groups of tongue specialists and dental plaque specialists, indicating that oral TM7s are “picky” regarding their desired habitat within the mouth. While plaque specialists associated with TM7 from environmental samples from an evolutionary and functional perspectives, tongue specialists associated with TM7 from animal gut. These findings indicate an ecological resemblance between the plaque environment and non-host environments such as soil and sediment from a microbial point of view, suggesting that the plaque environment may have served as a stepping stone for environmental microbes to adapt to host environments for some clades of human associated microbes. Additionally, I revealed that prophages are widespread amongst oral-associated TM7, while absent from environmental TM7, suggesting that prophages may have played a role in adaptation of TM7 to the host environment, perhaps by facilitating horizontal gene transfer. An in-depth description of my findings from the oral cavity is followed by a discussion of novel tools along with examples of their applications, and a discussion of good practices for scalable, high resolution exploration of 'omics data