** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS-TYPE 2 (PRRSV-2) IS A RAPIDLY EVOLVING RNA VIRUS IMPACTING ~30-50% OF BREEDING FARMS. SWINE PRODUCERS SEQUENCE THOUSANDS OF VIRUSES ANNUALLY AS PART OF DISEASE MANAGEMENT, BUT ARE FRUSTRATED BY LIMITATIONS IN TRANSLATING GENETIC DATA TO PHENOTYPIC INSIGHTS RELEVANT FOR DECISION-MAKING. OUR OBJECTIVE IS TO CREATE AN INTEGRATIVE DATA SCIENCE PLATFORM TO PREDICT THE IMMUNOGENIC AND EPIDEMIOLOGIC PHENOTYPE OF PRRSV-2 VARIANTS THROUGH BREAKING BARRIERS AND BUILDING CONNECTIVITY AMONG AI/ML ACROSS STRUCTURAL BIOLOGY, COMPUTATIONAL IMMUNOLOGY, AND GENOMIC EPIDEMIOLOGY.SPECIFICALLY, WE WILL APPLY UNSUPERVISED LEARNING TO IDENTIFY CLUSTERS (VARIANTS) OF CLOSELY RELATED GENETIC SEQUENCES WITHIN LARGE-SCALE DATABASES. WE WILL MEASURE STRUCTURAL DIVERGENCE BETWEEN VARIANTS (HYPOTHESIZED TO INFLUENCE IMMUNOGENICITY AND ANTIBODY BINDING) USING ALPHAFOLD 2.0, AN ARTIFICIAL INTELLIGENCE TOOL RECENTLY DEVELOPED FOR 3D STRUCTURAL PREDICTIONS OF PROTEIN FOLDING. WE WILL THEN APPLY MACHINE LEARNING TO EXPERIMENTAL DATA ON ANTIBODY CROSS-REACTIVITY AMONGST VARIANTS TO BUILD A MODEL THAT PREDICTS ANTIGENIC DISTANCE BASED ON GENETIC DISSIMILARITIES AND STRUCTURAL DIVERGENCE METRICS. LASTLY, WE WILL DEVELOP A MACHINE LEARNING ALGORITHM THAT PREDICTS A VARIANT'S EPIDEMIOLOGIC FITNESS (I.E., EXPANSION OF A GIVEN VARIANT THROUGH TIME) BASED ON ANTIGENIC DISTANCE, STRUCTURAL DIVERGENCE, AND PHYLOGENETIC FEATURES.WE WILL ALSO CREATE AN HTML-BASED VISUALIZATION PLATFORM THAT ALLOWS STAKEHOLDERS TO CLASSIFY AND CONTEXTUALIZE THEIR OWN SEQUENCES WITHIN THE BROADER PHENOTYPIC DIVERSITY OF THE VIRUS. THIS INTEGRATION OF BACK-END ANALYTICAL METHODS AND FRONT-END VISUALIZATION TOOLS WILL IMPROVE HUMAN-DATA INTERACTIONS SURROUNDING INTERPRETATION OF SEQUENCE DATA AND SUPPORT DECISION-MAKING ABOUT APPROPRIATE DISEASE MANAGEMENT AND IMMUNIZATION PRACTICES WITHIN THE SWINE INDUSTRY.