Genomic characterization of human adenoviruses through whole genome sequencing: Methods and public health implications.

Human adenoviruses cause significant morbidity, ranging from mild respiratory infections to severe diseases in immunocompromised individuals. Their public health impact is driven by high genetic diversity and frequent recombination, which often evade traditional surveillance like serology and partial sequencing. While conventional typing struggles with mixed infections and recombinant genomes, whole genome sequencing (WGS) offers a transformative solution, enabling accurate genotyping, variant detection, recombination mapping, and high-resolution phylogenetics. However, routine WGS adoption is hindered by inconsistent workflows, a lack of standardized bioinformatics protocols, and difficulties analyzing low-viral-load specimens. This review critically assesses the shift of adenovirus WGS from research to public health. We establish quality metrics, propose a standardized bioinformatics framework and present a strategic roadmap for operational integration, including harmonized metadata standards and interpretation guidelines linked to infection control. By addressing these challenges, we position WGS as a reliable foundation for monitoring HAdV evolution and mitigating emerging recombinant threats globally.