A New Comprehensive Catalog of the Human Virome Reveals Hidden Associations with Chronic Diseases

While there have been remarkable strides in microbiome research, the viral component of the microbiome has generally presented a more challenging target than the bacteriome. This is despite the fact that many thousands of shotgun sequencing runs from human metagenomic samples exist in public databases and all of them encompass large amounts of viral sequences. The lack of a comprehensive database for human-associated viruses, along with inadequate methods for high-throughput identification of highly divergent viruses in metagenomic data, has historically stymied efforts to characterize virus sequences in a comprehensive way. In this study, a new high-specificity and high-sensitivity bioinformatic tool, Cenote-Taker 2, was applied to thousands of human metagenome datasets, uncovering over 50,000 unique virus operational taxonomic units. Publicly available case-control studies were re-analyzed, and over 1,700 strong virus-disease associations were found.