Jillian Paull, Postdoctoral Researcher, Broad Institute

The burden of respiratory illness is substantial but the pathogens contributing to disease are often undifferentiated. Here, we pair unbiased high-depth metagenomic sequencing with an analysis pipeline that automatically produces high-quality genomes for over a dozen viruses. We sequenced 2000+ clinical respiratory isolates collected from Boston-area hospitals from 2023 to 2025, and showed that our pipeline: replicated a majority viral diagnoses; produced additional diagnoses, especially of rhinoviruses, for 6% of samples; identified rare viruses (ex: bocavirus) and non-respiratory viruses (ex: dengue); and provided automatic viral typing for viruses with multiple species or types (ex: adenovirus). We highlight the potential of a single, streamlined metagenomic sequencing pipeline to provide simultaneous surveillance of multiple viral pathogens.