Ndela, E. O. | Search bioRxiv

bioRxiv2025

A genomic atlas of the human gut virome elucidates genetic factors shaping host interactions

Viruses are key modulators of human gut microbiome composition and function. While metagenomic sequencing has enabled culture-independent discovery of gut bacteriophage diversity, existing genomic catalogues suffer from limited geographic representation, sparse taxonomic classification, and insufficient functional annotation, hindering detailed investigation into phage biology. Here, we present the Unified Human Gastrointestinal Virome (UHGV), a collection of 873,994 viral genomes from globally diverse populations that addresses these limitations. UHGV provides high-quality virome references with extensive host predictions, comprehensive functional annotations, protein structures, a classification framework for comparative analysis, and a web portal to facilitate data access. Using UHGV to profile worldwide metagenomes, we found that host range breadth is strongly associated with phage prevalence. Additionally, we identified diversity-generating retroelements and DNA methyltransferases as key factors enabling phage populations to access diverse hosts, revealing how specific genomic features contribute to global phage distribution patterns. UHGV is available at http://uhgv.jgi.doe.gov.

genomics↗

bioRxiv2021

Manual resolution of virome dark matter uncovers hundreds of viral families in the infant gut

The gut microbiome (GM) is shaped through infancy and plays a major role in determining susceptibility to chronic inflammatory diseases later in life. Bacteriophages (phages) are known to modulate bacterial populations in numerous ecosystems, including the gut. However, virome data is difficult to analyse because it mostly consists of unknown viruses, i.e. viral dark matter. Here, we manually resolved the viral dark matter in the largest human virome study published to date. Fecal viromes from a cohort of 647 infants at 1 year of age were deeply sequenced and analysed through successive rounds of clustering and curation. We uncovered more than ten thousand viral species distributed over 248 viral families falling within 17 viral order-level clades. Most of the defined viral families and orders were novel and belonged to the Caudoviricetes viral class. Bacterial hosts were predicted for 79% of the viral species using CRISPR spacers, including those in metagenomes from the same fecal samples. While Bacteroides-infecting Crassphages were present, novel viral families were more predominant, including phages infecting Clostridiales and Bifidobacterium. Phage lifestyles were determined for more than three thousand caudoviral species. Lifestyles were homogeneous at the family level for 149 Caudoviricetes families, including 32 families that were found to be virulent, while 117 were temperate. Virulent phage families were more abundant but temperate ones were more diverse and widespread. Together, the viral families found in this study represent a major expansion of existing bacteriophage taxonomy.

microbiology↗