Project Grant R03DE033993

INTEGRATED COMPUTATIONAL APPROACHES TO DETERMINE CONTRIBUTIONS OF THE ORAL VIROME - ABSTRACT THE ORAL CAVITY IS A COMPLEX ENVIRONMENT WHERE A DIVERSE ARRAY OF ORGANISMS COEXISTS IN DYNAMIC INTERPLAY WITH THE HUMAN IMMUNE SYSTEM. WHILE BACTERIA, ARCHAEA, AND FUNGI HAVE TRADITIONALLY BEEN THE FOCUS OF RESEARCH ON THE HUMAN MICROBIOME, RECENT STUDIES HAVE HIGHLIGHTED THE SIGNIFICANT ROLE OF VIRUSES IN SHAPING THE ORAL MICROENVIRONMENT. THESE SUBMICROSCOPIC AGENTS, COLLECTIVELY KNOWN AS THE VIROME, INCLUDE EUKARYOTIC VIRUSES, PROKARYOTIC (PHAGES) VIRUSES, AND CO-INFECTIVE (VIROPHAGES) VIRUSES ARE CRUCIAL TO MAINTAINING HEALTH AND MAY PLAY A ROLE IN THE DEVELOPMENT AND PERSISTENCE OF DISEASES. IN OCEAN AND SOIL COMMUNITIES, VIRUSES HAVE BEEN FOUND TO INFLUENCE BIOGEOCHEMICAL PROCESSES AND CONTROL MICROBIAL POPULATIONS THROUGH INFECTION AND LYSIS. SIMILARLY, IN THE HUMAN ORAL CAVITY, VIRUSES MAY HAVE A SUBSTANTIAL IMPACT ON ORAL HEALTH. ALTHOUGH RESEARCH EFFORTS FOCUSED ON THE ORAL VIROME ARE RELATIVELY NEW, RECENT TECHNOLOGICAL ADVANCEMENTS HAVE MADE IT POSSIBLE TO EXPLORE THIS AREA MORE COMPREHENSIVELY. HIGH-THROUGHPUT SEQUENCING AND SOPHISTICATED VIRAL DISCOVERY TOOLS HAVE ENABLED RESEARCHERS TO DELVE DEEPER INTO THE SIGNIFICANCE OF VIRAL COMMUNITIES. WHILE THERE HAVE BEEN A FEW RECENT STUDIES OF THE VIROME IN THE ORAL CAVITY PROVIDING PRELIMINARY EVIDENCE OF ITS IMPORTANCE, THERE EXISTS A LARGE UNTAPPED RESOURCE IN THE FORM OF HUNDREDS OF PUBLISHED METAGENOMIC AND METATRANSCRIPTOMIC STUDIES OF THE ORAL CAVITY IN VARYING STATES OF HEALTH AND DISEASE THAT HAVE ONLY BEEN USED TO STUDY THE TRADITIONAL MICROBIOME. HERE WE PROPOSE TO MINE THIS RESOURCE USING INNOVATIVE ALGORITHMIC APPROACHES AND MULTI-OMIC ANALYSIS TOOLS TO PURSUE A COMPREHENSIVE EXAMINATION OF THE ORAL VIROME AND ITS INTERACTIONS WITH THE MICROBIOME. BY SHEDDING LIGHT ON THE ROLE OF VIRUSES IN MAINTAINING ORAL HEALTH AND CONTRIBUTING TO DISEASE, THIS RESEARCH WILL ILLUMINATE A NEGLECTED MEMBER OF THE ORAL MICROENVIRONMENT AND POTENTIALLY HAVE FAR-REACHING IMPLICATIONS IN THE SEARCH FOR ALTERNATIVES TO ANTIBIOTICS, SUCH AS PHAGE THERAPIES. UNDERSTANDING THE INTRICATE DYNAMICS OF THE ORAL MICROENVIRONMENT WILL INSPIRE NEW APPROACHES TO PROMOTE ORAL HEALTH AND PREVENT/MANAGE ORAL DISEASES MORE EFFECTIVELY.