Uncultured prokaryotic genomes in the spotlight: An examination of publicly available data from metagenomics and single-cell genomics
Open accessAbstract
Owing to the ineffectiveness of traditional culture techniques for the vast majority of microbial species, culture-independent analyses utilizing next-generation sequencing and bioinformatics have become essential for gaining insight into microbial ecology and function. This mini-review focuses on two essential methods for obtaining genetic information from uncultured prokaryotes, metagenomics and single-cell genomics. We analyzed the registration status of uncultured prokaryotic genome data from major public databases and assessed the advantages and limitations of both the methods. Metagenomics generates a significant quantity of sequence data and multiple prokaryotic genomes using straightforward experimental procedures. However, in ecosystems with high microbial diversity, such as soil, most genes are presented as brief, disconnected contigs, and lack association of highly conserved genes and mobile genetic elements with individual species genomes. Although technically more challenging, single-cell genomics offers valuable insights into complex ecosystems by providing strain-resolved genomes, addressing issues in metagenomics. Recent technological advancements, such as long-read sequencing, machine learning algorithms, and in silico protein structure prediction, in combination with vast genomic data, have the potential to overcome the current technical challenges and facilitate a deeper understanding of uncultured microbial ecosystems and microbial dark matter genes and proteins. In light of this, it is imperative that continued innovation in both methods and technologies take place to create high-quality reference genome databases that will support future microbial research and industrial applications.
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Comparative genomic analyses usually test for correlations between traits.
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From A phylogenetic approach to comparative genomics (2025) · cites this paper as [79]
The sections on genetic diversity and prokaryotic genes compare genome datasets, but do not describe what comparative genomic analyses usually test. Searches for trait correlations and associations between genomic features found no passage addressing that claim; page numbers were not available in our copy. (LLM, conf=0.72)
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A phylogenetic approach to comparative genomics
Dewar, A. E., Belcher, L. J., & West, S. A. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-024-00803-0 · Cited by 41 · see citing works
- Authors
- Arikawa, K., & Hosokawa, M.
- Affiliations
- Waseda University (JP)
- Corresponding author
- Hosokawa, Masahito
- ORCID
- Hosokawa, Masahito
- Venue
- Computational and Structural Biotechnology Journal
- Published
- 2023-01
- Volume
- 21
- Pages
- 4508-4518
- ISSN
- 2001-0370 (ISSN-L)
- PMC
- PMC10523443
- OpenAlex
- W4386690165
- Cited by
- 13
- References
- 6
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Computational and Structural Biotechnology Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (21H01733)
- 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
- metagenomics, single-cell genomics, microbial dark matter, reference genome database, soil microbial diversity, contig assembly, mobile genetic elements, long-read sequencing
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