Hi-C deconvolution of a human gut microbiome yields high-quality draft genomes and reveals plasmid-genome interactions
Open accessAbstract
The assembly of high-quality genomes from mixed microbial samples is a long-standing challenge in genomics and metagenomics. Here, we describe the application of ProxiMeta, a Hi-C-based metagenomic deconvolution method, to deconvolve a human fecal metagenome. This method uses the intra-cellular proximity signal captured by Hi-C as a direct indicator of which sequences originated in the same cell, enabling culture-free de novo deconvolution of mixed genomes without any reliance on a priori information. We show that ProxiMeta deconvolution provides results of markedly high accuracy and sensitivity, yielding 50 near-complete microbial genomes (many of which are novel) from a single fecal sample, out of 252 total genome clusters. ProxiMeta outperforms traditional contig binning at high-quality genome reconstruction. ProxiMeta shows particularly good performance in constructing high-quality genomes for diverse but poorly-characterized members of the human gut. We further use ProxiMeta to reconstruct genome plasmid content and sharing of plasmids among genomes—tasks that traditional binning methods usually fail to accomplish. Our findings suggest that Hi-C-based deconvolution can be useful to a variety of applications in genomics and metagenomics.
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Hi-C binning has been used effectively on human feces and in ruminants.
“Hi-C binning has been used effectively on human feces (Press et al., 2017) as well as in ruminants (Stewart et al., 2018).”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Press et al., 2017
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- Authors
- Press, M. O., Wiser, A. H., Kronenberg, Z. N., Langford, K. W., Shakya, M., Lo, C.-C., Mueller, K. A., Sullivan, S. T., Chain, P. S. G., & Liachko, I.
- Affiliations
- Los Alamos National Laboratory (US)
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2017-10-05
- OpenAlex
- W2767898240
- Cited by
- 103
- References
- 47
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 13 · 2021: 19 · 2020: 8 · 2019: 12 · 2018: 3
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Keywords
- human gut microbiome, fecal metagenome, draft genome assembly, plasmid sharing, contig binning
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