Genome-Wide Comparative Analyses of Herpesvirus Populations

Herpesviruses are a large family of DNA viruses that infect two-thirds of all humans and contribute billions of dollars to the global economic burden of disease. Like many other DNA viruses, herpesviruses were long thought to possess negligible levels of genetic diversity. However, this assumption was rooted in a simplified, single-reference model of herpesvirus genomes that ignored within-sample variation and lacked access to complex genomic regions. In this talk, I will first describe my early efforts to challenge this paradigm using traditional short-read sequencing approaches. I will then present my work using high-fidelity long reads (PacBio HiFi) to characterize tandem repeat loci in herpesvirus genomes.

These efforts have culminated in TRIDENT, a novel computational tool developed in collaboration with Dr. Anton Bankevich, which is capable of characterizing complex tandem repeat patterns across thousands of individual PacBio HiFi reads. In addition to revealing substantial genomic diversity both within and between herpesvirus infections, these methods have enabled the first truly complete, telomere-to-telomere (T2T) herpesvirus genome assemblies, and established a methodological foundation for high-throughput T2T assembly at scale. Together, these advances provide the substrate for graph-based pangenomics approaches that allow us to study herpesvirus genomes not as static reference sequences, but as dynamic populations of related genomic variants — a biological reality that has, until now, remained out of reach.

Contact

  Donna McMinn
  dlp18@psu.edu
  +1 814-935-3444