Accurate and complete genomes from metagenomes
Open accessPublished version of a preprint
Abstract
Genomes are an integral component of the biological information about an organism; thus, the more complete the genome, the more informative it is. Historically, bacterial and archaeal genomes were reconstructed from pure (monoclonal) cultures, and the first reported sequences were manually curated to completion. However, the bottleneck imposed by the requirement for isolates precluded genomic insights for the vast majority of microbial life. Shotgun sequencing of microbial communities, referred to initially as community genomics and subsequently as genome-resolved metagenomics, can circumvent this limitation by obtaining metagenome-assembled genomes (MAGs); but gaps, local assembly errors, chimeras, and contamination by fragments from other genomes limit the value of these genomes. Here, we discuss genome curation to improve and, in some cases, achieve complete (circularized, no gaps) MAGs (CMAGs). To date, few CMAGs have been generated, although notably some are from very complex systems such as soil and sediment. Through analysis of about 7000 published complete bacterial isolate genomes, we verify the value of cumulative GC skew in combination with other metrics to establish bacterial genome sequence accuracy. The analysis of cumulative GC skew identified potential misassemblies in some reference genomes of isolated bacteria and the repeat sequences that likely gave rise to them. We discuss methods that could be implemented in bioinformatic approaches for curation to ensure that metabolic and evolutionary analyses can be based on very high-quality genomes.
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The MAGs generated in this study potentially harbor errors such as fragmentation, assembly breaks and contamination.
“Moreover, although we used a state-of-the-art bioinformatics pipeline to generate and quality control MAGs to represent study-specific strains (many of which are new or uncultivated), they still potentially harbor errors (such as fragmentation, assembly breaks and contamination) 53 .”
From A gut microbial signature for combination immune checkpoint blockade across cancer types (2024) · cites this paper as [53]
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Self-citationEvidence for extensive horizontal gene transfer from the draft genome of a tardigrade
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Self-citationComposite Metagenome-Assembled Genomes Reduce the Quality of Public Genome Repositories
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Metagenome Analysis Exploiting High-Throughput Chromosome Conformation Capture (3C) Data
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Self-citation
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A unified catalog of 204,938 reference genomes from the human gut microbiome
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Metabolic independence drives gut microbial colonization and resilience in health and disease
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Integrated molecular approaches for fermented food microbiome research
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- Authors
- Chen, L.-X., Anantharaman, K., Shaiber, A., Eren, A. M., & Banfield, J. F.
- Affiliations
- University of California, Berkeley (US)
- University of Wisconsin–Madison (US)
- University of Chicago (US)
- Marine Biological Laboratory (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Eren, A. Murat
- Banfield, Jillian F.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2020-03
- Volume
- 30
- Issue
- 3
- Pages
- 315-333
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC7111523
- OpenAlex
- W3011678041
- Cited by
- 401
- References
- 148
- Citations by year
- 2026: 38 · 2025: 34 · 2024: 68 · 2023: 67 · 2022: 75 · 2021: 78 · 2020: 37 · 2019: 1 · 2017: 1 · 2015: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Genome Canada
- Lawrence Berkeley National Laboratory's Watershed Function Scientific Focus Area (DE-AC02-05CH11231)
- Office of Science and Office of Biological and Environmental Research
- National Institutes of Health (RAI092531A, R01-GM109454)
- Chan Zuckerberg Biohub
- Innovative Genomics Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Physical Sciences › Environmental Science › Ecology › Environmental DNA in Biodiversity Studies
- Keywords
- metagenome-assembled genomes, genome curation, complete genome sequence, genome completeness, GC skew, misassembly detection, bacterial genomes, genome assembly errors, chimeras, contamination
- MeSH terms
- Genome, Bacterial, Genome, Archaeal, Metagenome, Metagenomics, Data Curation
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