Location: Virus and Prion Research
Project Number: 5030-32000-231-114-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Sep 15, 2024
End Date: Sep 14, 2026
Objective:
Develop a software pipeline that uses genomic information to automatically prioritize and select endemic IAV strains collected in surveillance that have high zoonotic potential.
Approach:
Our computational approach will rank zoonotic risk and account for genetic diversity, geographic distribution and detection frequency, host breadth, reassortment history, and phenotypic properties of the IAV in animal populations. Specifically, we will:
1. Develop and validate next-generation causal machine learning models. The tools will be evaluated for their ability to:
a. Predict the antigenic novelty of hemagglutinin (HA) genes (i) within animal populations relative to circulating viruses and (ii) antigenic novelty to humans.
b. Predict interspecies spillover risk using proxies derived from HA genetic sequence data, i.e., pH stability, protein stability, receptor binding, or replication in human respiratory cells.
2. Develop (i) a methodology for reconstructing the reassortment history of IAV and
(ii) quantify how reassortment drives antigenic and phenotypic novelty and evolution of endemic IAV.
3. Deploy a software program that integrates genomic, geographic, and host data with the phenotype prediction algorithms and reassortment history information to make informed and representative selections for strain characterization.