Fred Hutchinson Cancer Center

WOMEN'S HEALTH INITIATIVE (WHI) CLINICAL COORDINATING CENTER - TASK AREA A AND A2

PONTIUS PARKING OCT 2024 PONTIUS RENT OCT 2024

STATEMENT OF WORK – FRED HUTCHINSON CANCER RESEARCH CENTER BLOOM LAB THE BLOOM LAB WILL PERFORM EXPERIMENTAL AND COMPUTATIONAL WORK TO CHARACTERIZE INFLUENZA VIRUS EVOLUTION. IN PROJECT 3, THEY WILL USE MUTATIONAL ANTIGENIC PROFILING TO EXPERIMENTALLY MAP THE EFFECTS OF VIRAL MUTATIONS ON IMMUNE RECOGNITION. IN THE COMPUTATIONAL CORE, THEY WILL DEVELOP TOOL TO ANALYZE AND VISUALIZE THE EFFECTS OF VIRAL MUTATIONS. BEDFORD LAB THE BEDFORD LAB AT THE FRED HUTCH WILL BE RESPONSIBLE FOR IMPLEMENTATION OF PROJECT 3, AIM 2 (PREDICT AND VISUALIZE WHICH CIRCULATING CLADES OF INFLUENZA WILL DOMINATE USING PHYLOGENETIC ANALYSES, AGE-STRUCTURED SEROLOGY, MUTATIONAL ANTIGENIC PROFILING, AND VACCINATION COVERAGE). FOR THIS, THE BEDFORD LAB WILL DEVELOP AND IMPLEMENT A PREDICTIVE MODEL THAT INCORPORATES DATA GENERATED BY THE BLOOM LAB FOR PROJECT 3, AIM 1 AS WELL AS OTHER SEROLOGICAL DATA GENERATED BY THE CENTER. THE BEDFORD LAB WILL INTEGRATE THIS SEROLOGICAL DATA WITH PUBLICLY AVAILABLE INFLUENZA GENETIC SEQUENCE DATA. THIS MODEL WILL ESTIMATE THE EVOLUTIONARY TRAJECTORY OF THE INFLUENZA VIRUS POPULATION. THE BEDFORD LAB WILL ALSO BE RESPONSIBLE FOR CONTRIBUTING KEY COMPONENTS TO THE MODELING AND COMPUTATIONAL CORE. THIS PRIMARILY CONSISTS OF USING THE EXISTING NEXTSTRAIN FRAMEWORK TO SUPPORT ANALYSIS AND SHARING OF DATA GENERATED BY THE CENTER. THE BEDFORD LAB ALREADY WORKS CLOSELY WITH WHO COLLABORATING CENTERS TO INTEGRATE AND ANALYZE INFLUENZA SEROLOGICAL AND SEQUENCE DATA. THE INTERACTION WITH THE CENTER SHOULD BE SIMILAR. THE BEDFORD LAB WILL DEVELOP A COMPUTATIONAL PREDICTIVE MODEL TO (1) ESTIMATE THE HUMAN POPULATION IMMUNE LANDSCAPE AGAINST DIFFERENT STRAINS OF SEASONAL INFLUENZA AND (2) PREDICT UPCOMING STRAIN DYNAMICS FOR THE INFLUENZA VIRUS POPULATION. DATA TO INFORM (1) WILL BE INTEGRATED FROM THE DEEP MUTATIONAL SCANNING (DMS) EXPERIMENTS CONDUCTED BY THE BLOOM LAB ALONGSIDE OTHER SEROLOGICAL DATA GENERATED BY OTHER STUDIES IN THE CENTER. WITH AN ESTIMATE OF POPULATION IMMUNITY IN HAND, WE WILL INFER FITNESS VALUES FOR CIRCULATING VIRUSES AND USE THESE FITNESS VALUES TO PREDICT WHETHER STRAINS INCREASE IN FREQUENCY OR DECLINE. THIS MODEL WILL BE IMPLEMENTED IN AN OPEN SOURCE PYTHON FRAMEWORK FOLLOWING OUR EXISTING STRAIN FORECASTING CODEBASE. THE PRIMARY ADDITIONS FOR THE CURRENT PROJECT ARE TO: (1) INTEGRATE HUMAN POPULATION IMMUNITY THROUGH DMS AND SEROLOGICAL DATA AND (2) INCORPORATE A GEOGRAPHICALLY STRUCTURED VIRUS POPULATION. THIS MODEL WILL BE RUN CONTINUALLY AS NEW DATA BECOMES AVAILABLE AND UP-TO-DATE FORECASTS PROVIDED FROM THE NEXTSTRAIN.ORG WEBSITE. THE BEDFORD LAB WILL EXTEND THE NEXTSTRAIN PLATFORM TO INTEGRATE AND SHARE DATA GENERATED BY THE CENTER. THE BEDFORD LAB WILL CREATE A NEW CEIRR NEXTSTRAIN GROUP THAT WILL HOUSE ALL THE CEIRR ANALYSES. THIS GROUP ALLOWS FOR BOTH PUBLIC DATASETS AND FOR PRIVATE DATASETS, BOTH OF WHICH SHOULD BE USEFUL FOR THESE PURPOSES. THE BEDFORD LAB WILL ALSO HOUSE A DATABASE OF SEROLOGICAL AND SEQUENCE DATA FOR CENTER PROJECTS CORRESPONDING TO THE WAY THE BEDFORD LAB CURRENTLY HOUSES WHO COLLABORATING CENTER DATA.