Improving gut virome comparisons using predicted phage host information.

Area of Science:

• Microbiology
• Bioinformatics
• Systems Biology

Background:

• The human gut virome is dominated by bacteriophages (phages), viruses that infect bacteria.
• High individual specificity and dynamism of gut phages complicate cross-study comparisons.
• Existing phage taxonomy provides limited insight into host interactions and functional roles.

Purpose of the Study:

• To propose and validate predicted phage host families (PHFs) as a functionally relevant unit for phage classification.
• To enhance cross-study comparisons of the gut virome by providing a biologically meaningful framework.
• To assess the utility of PHFs in identifying disease-specific virome signatures, such as in inflammatory bowel disease.

Main Methods:

• Bioinformatic prediction of phage hosts and validation against Hi-C sequencing data in human and mouse fecal samples.
• Analysis of ecological distances and longitudinal virome stability using PHFs compared to viral contigs.
• Reanalysis of a large metagenomics dataset (>1,000 samples) to evaluate PHF prevalence and disease association.

Main Results:

• Bioinformatic phage host predictions demonstrate high accuracy at the host family level.
• PHFs significantly reduce intra- and interindividual ecological distances and improve virome stability over time.
• PHFs are prevalent across individuals and facilitate the detection of inflammatory bowel disease-associated virome patterns.

Conclusions:

• Predicted phage host families (PHFs) offer a robust, functionally relevant classification system for the gut virome.
• PHFs improve the comparability and biological interpretability of metagenomic virome studies.
• This framework aids in understanding gut microbiome ecology and identifying disease-specific viral signatures.