Best practices for herpesvirus genomics

Abstract: Since the introduction of high-throughput, massively parallel deep sequencing, the field of viral genomics has blossomed. A single viral genome – even for large double-stranded DNA herpesviruses – can now be sequenced in a matter of hours, and with an initial draft assembled in as little as one day. This is a vast improvement on the multi-year and multi-lab efforts required to sequence the first-ever genome of each herpesvirus species. However, these genomes still present many challenges in the form of extensive repeat regions, rampant recombination, and structural variants such as isomers – all of which contribute to the minor variants and standing population diversity found in these infections. A wide range of experimental and computational methods have emerged to support downstream genome analyses, including phylogenetics, transcriptomics, and chromatin profiling. Yet experimental design, computational parameters, and even terminology can lead to very different interpretations of viral biology based on these genomic approaches. Since 2017, each in-person meeting of the International Herpesvirus Workshop (IHW) has included an open community-wide discussion of methods for herpesvirus genomics. Here we summarize the current best practices in herpesvirus genomics, spanning genome sequencing, population diversity, transcriptomic and epigenomic analyses, and data sharing. We also identify areas requiring further standardization, including genome annotation and reporting practices. By sharing these community-driven recommendations, this review aims to support reproducible and comparable research across the field. This will facilitate the adaptation of future methodological advances, even as our understanding of these diverse viruses keeps pace with viral evolution. Feedback on this preprint is welcome! Submit feedback here: https://forms.gle/N9iDgF8Dmgj9yKyu9