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Exploring bacterial diversity via a curated and searchable snapshot of archived DNA sequences

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Blackwell, Grace A., Hunt, Martin, Malone, Kerri M., Lima, Leandro, Horesh, Gal, Alako, Blaise T. F., Thomson, Nicholas R., Iqbal, Zamin·2021·PLOS Biology
DOI 10.1371/journal.pbio.3001421PMC PMC8577725
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Abstract

The open sharing of genomic data provides an incredibly rich resource for the study of bacterial evolution and function and even anthropogenic activities such as the widespread use of antimicrobials. However, these data consist of genomes assembled with different tools and levels of quality checking, and of large volumes of completely unprocessed raw sequence data. In both cases, considerable computational effort is required before biological questions can be addressed. Here, we assembled and characterised 661,405 bacterial genomes retrieved from the European Nucleotide Archive (ENA) in November of 2018 using a uniform standardised approach. Of these, 311,006 did not previously have an assembly. We produced a searchable COmpact Bit-sliced Signature (COBS) index, facilitating the easy interrogation of the entire dataset for a specific sequence (e.g., gene, mutation, or plasmid). Additional MinHash and pp-sketch indices support genome-wide comparisons and estimations of genomic distance. Combined, this resource will allow data to be easily subset and searched, phylogenetic relationships between genomes to be quickly elucidated, and hypotheses rapidly generated and tested. We believe that this combination of uniform processing and variety of search/filter functionalities will make this a resource of very wide utility. In terms of diversity within the data, a breakdown of the 639,981 high-quality genomes emphasised the uneven species composition of the ENA/public databases, with just 20 of the total 2,336 species making up 90% of the genomes. The overrepresented species tend to be acute/common human pathogens, aligning with research priorities at different levels from individual interests to funding bodies and national and global public health agencies.

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  • The problem of non-independence is complicated even further by how unrepresentative most genomic datasets are of natural communities, owing to biases in which species have been sequenced more frequently.

    “The problem of non-independence is complicated even further by how unrepresentative most genomic datasets are of natural communities, owing to biases in which species have been sequenced more frequently (Fig. 2)27–29.”

    From A phylogenetic approach to comparative genomics (2025) · cites this paper as [27]

    The Abstract reports a strongly uneven species composition in the ENA/public bacterial genome databases: 20 of 2,336 species account for 90% of the genomes. The Discussion links this skew to sequencing priorities and says the archive does not capture bacterial diversity well. The paper does not establish that most genomic datasets, beyond the bacterial archives it examines, are unrepresentative of natural communities. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Genomic databases are biased towards taxonomic groups that have been sequenced more frequently.

    “This problem is made worse because genomic databases are biased towards taxonomic groups that have been sequenced more frequently27–29 (Fig. 2).”

    From A phylogenetic approach to comparative genomics (2025) · cites this paper as [27]

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Authors
Blackwell, G. A., Hunt, M., Malone, K. M., Lima, L., Horesh, G., Alako, B. T. F., Thomson, N. R., & Iqbal, Z.
Affiliations
  • European Bioinformatics Institute (GB)
  • Wellcome Sanger Institute (GB)
Corresponding author
  • Blackwell, Grace A.
  • Hunt, Martin
  • Malone, Kerri M.
  • Lima, Leandro
  • Horesh, Gal
  • Alako, Blaise T. F.
  • Thomson, Nicholas R.
  • Iqbal, Zamin
ORCID
Venue
PLOS Biology
Publisher
Public Library of Science (PLoS)
Published
2021-11-09
Volume
19
Issue
11
Pages
e3001421
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.3001421
PMC
PMC8577725
OpenAlex
W3212599762
Cited by
111
References
4
Citations by year
2026: 15 · 2025: 29 · 2024: 26 · 2023: 18 · 2022: 20 · 2021: 3
FWCI
5.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (206194)
  • Wellcome Trust/Newton Fund-MRC Collaborative Award (200205)
  • Bill and Melinda Gates Foundation (OPP1133541)
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 › Computer Science › Information Systems › Research Data Management Practices
Keywords
bacterial diversity, bacterial genomes, genome assembly, MinHash, phylogenetic relationships, human pathogens, antimicrobial resistance, European Nucleotide Archive
MeSH terms
Bacteria, Base Sequence, DNA, Bacterial, Species Specificity, Drug Resistance, Bacterial, Biodiversity, Data Curation

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