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Structural and Functional Disparities within the Human Gut Virome in Terms of Genome Topology and Representative Genome Selection
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Abstract
Circularity confers protection to viral genomes where linearity falls short, thereby fulfilling the form follows function aphorism. However, a shift away from morphology-based classification toward the molecular and ecological classification of viruses is currently underway within the field of virology. Recent years have seen drastic changes in the International Committee on Taxonomy of Viruses’ operational definitions of viruses, particularly for the tailed phages that inhabit the human gut. After the abolition of the order Caudovirales, these tailed phages are best defined as members of the class Caudoviricetes. To determine the epistemological value of genome topology in the context of the human gut virome, we designed a set of seven experiments to assay the impact of genome topology and representative viral selection on biological interpretation. Using Oxford Nanopore long reads for viral genome assembly coupled with Illumina short-read polishing, we showed that circular and linear virus genomes differ remarkably in terms of genome quality, GC skew, transfer RNA gene frequency, structural variant frequency, cross-reference functional annotation (COG, KEGG, Pfam, and TIGRfam), state-of-the-art marker-based classification, and phage–host interaction. Furthermore, the disparity profile changes during dereplication. In particular, our phage–host interaction results demonstrated that proportional abundances cannot be meaningfully compared without due regard for genome topology and dereplication threshold, which necessitates the need for standardized reporting. As a best practice guideline, we recommend that comparative studies of the human gut virome always report the ratio of circular to linear viral genomes along with the dereplication threshold so that structural and functional metrics can be placed into context when assessing biologically relevant metagenomic properties such as proportional abundance.
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Metadata
- Authors
- Veldsman, W. P., Yang, C., Zhang, Z., Huang, Y., Chowdhury, D., & Zhang, L.
- Affiliations
- Hong Kong Baptist University (HK)
- BGI Research (CN)
- Corresponding author
- Zhang, Lu
- Venue
- Viruses
- Publisher
- MDPI AG
- Published
- 2024-01-17
- Volume
- 16
- Issue
- 1
- Pages
- 134
- ISSN
- 1999-4915 (ISSN-L)
- PMC
- PMC10820185
- OpenAlex
- W4390942168
- Cited by
- 2
- References
- 2
- Citations by year
- 2026: 1 · 2024: 1
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Viruses (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- BGI-Shenzhen (BGIRSZ20220014, HKBU 22201419, RC-SGT2/19-20/SCI/007, IRCMS/19-20/D02, 2021A1515012226)
- Hong Kong Research Grant Council Early Career Scheme (BGIRSZ20220014, HKBU 22201419, RC-SGT2/19-20/SCI/007, IRCMS/19-20/D02, 2021A1515012226)
- HKBU Start-up Grant Tier 2 (BGIRSZ20220014, HKBU 22201419, RC-SGT2/19-20/SCI/007, IRCMS/19-20/D02, 2021A1515012226)
- HKBU IRCMS (BGIRSZ20220014, HKBU 22201419, RC-SGT2/19-20/SCI/007, IRCMS/19-20/D02, 2021A1515012226)
- Guangdong Basic and Applied Basic Research Foundation (BGIRSZ20220014, HKBU 22201419, RC-SGT2/19-20/SCI/007, IRCMS/19-20/D02, 2021A1515012226)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- human gut virome, tailed phages, Caudoviricetes, phage-host interactions
- MeSH terms
- Virome, Bacteriophages, Biological Assay, Humans, Genome, Viral, Metagenome
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