Integrative approaches to decipher influenza evolution, antibody responses, and AI-driven specificity prediction
Year: 2025
Type: dissertation
Abstract: The ongoing threat of viral pathogens, such as SARS-CoV-2 and influenza Viruses, highlights the urgent need to understand immune responses and viral evolution to guide therapeutic and vaccine development.This dissertation integrates high-throughput experimental techniques and artificial intelligence (AI) to address key questions in virus-immunity interactions through three interconnected research areas: (1) deep mutational scanning (DMS) to map sequencefunction relationships in influenza viral proteins; (2) large-scale analysis of antibody responses to SARS-CoV-2 and influenza; and (3) development of AI models to predict antibody specificity.Chapter 1 introduces the rapid advancement of high-throughput and AI methodologies for studying immune responses and viral evolution.Chapter 2 presents a robust DMS pipeline that reveals high N-terminal tolerance in the nuclear export protein (NEP) and identifies charge-driven epistasis as a constraint on neuraminidase (NA) antigenic evolution.Chapter 3 describes largescale profiling of antibody repertoires across viral pathogens, identifying critical residues in IGHV1-69 broadly neutralizing antibodies that target the hemagglutinin (HA) stem.Chapter 4 showcases AI-driven models for predicting antibody specificity and highlights their promise for therapeutic design.Chapter 5 synthesizes key findings and outlines future directions.By combining high-throughput experimentation with AI, this dissertation advances our understanding of host-pathogen interactions and provides new tools for vaccine design and immunotherapy.Finally, I want to express my deepest gratitude to my parents, who raised me to be independent, resilient, and strong-minded.Their unwavering support, quiet strength, and belief in my potential laid the foundation for everything I've accomplished.They taught me to face challenges with determination, to pursue knowledge with curiosity, and to remain grounded through both success and hardship.Because of them, I've had the courage to follow my passion for science-from my early days in bioengineering to the countless hours spent coding, experimenting, and exploring the unknown.This journey, completed in April 2025, is not only a reflection of my own perseverance but also a tribute to the values they instilled in me.Thank you for giving me the strength to walk this path-and the freedom to make it my own.To everyone who has walked this path with me-thank you.This dissertation is a shared achievement, and I look forward to where our efforts will lead next.
Author: Wang, Yiquan
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7220797358