Improving gut virome comparisons using predicted phage host information
ABSTRACT The human gut virome is predominantly made up of bacteriophages (phages), viruses that infect bacteria. Metagenomic studies have revealed that phages in the gut are highly individual specific and dynamic. These features make it challenging to perform meaningful cross-study comparisons. Whil...
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American Society for Microbiology
2025-05-01
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| Series: | mSystems |
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| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01364-24 |
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| author | Michael Shamash Anshul Sinha Corinne F. Maurice |
| author_facet | Michael Shamash Anshul Sinha Corinne F. Maurice |
| author_sort | Michael Shamash |
| collection | DOAJ |
| description | ABSTRACT The human gut virome is predominantly made up of bacteriophages (phages), viruses that infect bacteria. Metagenomic studies have revealed that phages in the gut are highly individual specific and dynamic. These features make it challenging to perform meaningful cross-study comparisons. While several taxonomy frameworks exist to group phages and improve these comparisons, these strategies provide little insight into the potential effects phages have on their bacterial hosts. Here, we propose the use of predicted phage host families (PHFs) as a functionally relevant, qualitative unit of phage classification to improve these cross-study analyses. We first show that bioinformatic predictions of phage hosts are accurate at the host family level by measuring their concordance to Hi-C sequencing-based predictions in human and mouse fecal samples. Next, using phage host family predictions, we determined that PHFs reduce intra- and interindividual ecological distances compared to viral contigs in a previously published cohort of 10 healthy individuals, while simultaneously improving longitudinal virome stability. Lastly, by reanalyzing a previously published metagenomics data set with >1,000 samples, we determined that PHFs are prevalent across individuals and can aid in the detection of inflammatory bowel disease-specific virome signatures. Overall, our analyses support the use of predicted phage hosts in reducing between-sample distances and providing a biologically relevant framework for making between-sample virome comparisons.IMPORTANCEThe human gut virome consists mainly of bacteriophages (phages), which infect bacteria and show high individual specificity and variability, complicating cross-study comparisons. Furthermore, existing taxonomic frameworks offer limited insight into their interactions with bacterial hosts. In this study, we propose using predicted phage host families (PHFs) as a higher-level classification unit to enhance functional cross-study comparisons. We demonstrate that bioinformatic predictions of phage hosts align with Hi-C sequencing results at the host family level in human and mouse fecal samples. We further show that PHFs reduce ecological distances and improve virome stability over time. Additionally, reanalysis of a large metagenomics data set revealed that PHFs are widespread and can help identify disease-specific virome patterns, such as those linked to inflammatory bowel disease. |
| format | Article |
| id | doaj-art-bc6e65a40c0a47f3bef79a37a1609af2 |
| institution | DOAJ |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj-art-bc6e65a40c0a47f3bef79a37a1609af22025-08-20T03:07:24ZengAmerican Society for MicrobiologymSystems2379-50772025-05-0110510.1128/msystems.01364-24Improving gut virome comparisons using predicted phage host informationMichael Shamash0Anshul Sinha1Corinne F. Maurice2Department of Microbiology & Immunology, McGill University, Montreal, Quebec, CanadaDepartment of Microbiology & Immunology, McGill University, Montreal, Quebec, CanadaDepartment of Microbiology & Immunology, McGill University, Montreal, Quebec, CanadaABSTRACT The human gut virome is predominantly made up of bacteriophages (phages), viruses that infect bacteria. Metagenomic studies have revealed that phages in the gut are highly individual specific and dynamic. These features make it challenging to perform meaningful cross-study comparisons. While several taxonomy frameworks exist to group phages and improve these comparisons, these strategies provide little insight into the potential effects phages have on their bacterial hosts. Here, we propose the use of predicted phage host families (PHFs) as a functionally relevant, qualitative unit of phage classification to improve these cross-study analyses. We first show that bioinformatic predictions of phage hosts are accurate at the host family level by measuring their concordance to Hi-C sequencing-based predictions in human and mouse fecal samples. Next, using phage host family predictions, we determined that PHFs reduce intra- and interindividual ecological distances compared to viral contigs in a previously published cohort of 10 healthy individuals, while simultaneously improving longitudinal virome stability. Lastly, by reanalyzing a previously published metagenomics data set with >1,000 samples, we determined that PHFs are prevalent across individuals and can aid in the detection of inflammatory bowel disease-specific virome signatures. Overall, our analyses support the use of predicted phage hosts in reducing between-sample distances and providing a biologically relevant framework for making between-sample virome comparisons.IMPORTANCEThe human gut virome consists mainly of bacteriophages (phages), which infect bacteria and show high individual specificity and variability, complicating cross-study comparisons. Furthermore, existing taxonomic frameworks offer limited insight into their interactions with bacterial hosts. In this study, we propose using predicted phage host families (PHFs) as a higher-level classification unit to enhance functional cross-study comparisons. We demonstrate that bioinformatic predictions of phage hosts align with Hi-C sequencing results at the host family level in human and mouse fecal samples. We further show that PHFs reduce ecological distances and improve virome stability over time. Additionally, reanalysis of a large metagenomics data set revealed that PHFs are widespread and can help identify disease-specific virome patterns, such as those linked to inflammatory bowel disease.https://journals.asm.org/doi/10.1128/msystems.01364-24viromegut microbiomebacteriophagesbioinformaticsmicrobial interactions |
| spellingShingle | Michael Shamash Anshul Sinha Corinne F. Maurice Improving gut virome comparisons using predicted phage host information mSystems virome gut microbiome bacteriophages bioinformatics microbial interactions |
| title | Improving gut virome comparisons using predicted phage host information |
| title_full | Improving gut virome comparisons using predicted phage host information |
| title_fullStr | Improving gut virome comparisons using predicted phage host information |
| title_full_unstemmed | Improving gut virome comparisons using predicted phage host information |
| title_short | Improving gut virome comparisons using predicted phage host information |
| title_sort | improving gut virome comparisons using predicted phage host information |
| topic | virome gut microbiome bacteriophages bioinformatics microbial interactions |
| url | https://journals.asm.org/doi/10.1128/msystems.01364-24 |
| work_keys_str_mv | AT michaelshamash improvinggutviromecomparisonsusingpredictedphagehostinformation AT anshulsinha improvinggutviromecomparisonsusingpredictedphagehostinformation AT corinnefmaurice improvinggutviromecomparisonsusingpredictedphagehostinformation |