Cited by 286Gut microbiota and healthGenomics and Phylogenetic StudiesBacterial Identification and Susceptibility Testing

High-throughput microbial culturomics using automation and machine learning

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Huang, Yiming, Sheth, Ravi U., Zhao, Shijie, Cohen, Lucas A., Dabaghi, Kendall, Moody, Thomas, Sun, Yiwei, Ricaurte, Deirdre +6 more·2023·Nature Biotechnology

Abstract

Pure bacterial cultures remain essential for detailed experimental and mechanistic studies in microbiome research, and traditional methods to isolate individual bacteria from complex microbial ecosystems are labor-intensive, difficult-to-scale and lack phenotype-genotype integration. Here we describe an open-source high-throughput robotic strain isolation platform for the rapid generation of isolates on demand. We develop a machine learning approach that leverages colony morphology and genomic data to maximize the diversity of microbes isolated and enable targeted picking of specific genera. Application of this platform on fecal samples from 20 humans yields personalized gut microbiome biobanks totaling 26,997 isolates that represented >80% of all abundant taxa. Spatial analysis on >100,000 visually captured colonies reveals cogrowth patterns between Ruminococcaceae, Bacteroidaceae, Coriobacteriaceae and Bifidobacteriaceae families that suggest important microbial interactions. Comparative analysis of 1,197 high-quality genomes from these biobanks shows interesting intra- and interpersonal strain evolution, selection and horizontal gene transfer. This culturomics framework should empower new research efforts to systematize the collection and quantitative analysis of imaging-based phenotypes with high-resolution genomics data for many emerging microbiome studies.

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  • Large-scale cultivation projects and massive metagenomic assembly efforts are quickly expanding and completing reference databases needed for taxonomic profiling tools.

    “However, particularly for the gut microbiome, largescale cultivation projects 134 and massive metagenomic assembly efforts 135 are quickly expanding and completing reference databases needed for taxonomic profiling tools. 136”

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  1. [10]Allegrucci M Sauer K Characterization of colony morphology variants isolated from Streptococcus pneumoniae biofilms J. Bacteriol. 2007 189 2030 2038 17189375 PMC1855740
  2. [63]Huang, Y. et al. High-throughput microbial culturomics using automation and machine learning. WGS of isolates collection. Sequence Read Archive. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA745993 (2023). PMC10567565 36805559
  3. [64]Huang, Y. et al. High-throughput microbial culturomics using automation and machine learning. GitHub. https://github.com/hym0405/CAMII (2023). PMC10567565 36805559

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Authors
Huang, Y., Sheth, R. U., Zhao, S., Cohen, L. A., Dabaghi, K., Moody, T., Sun, Y., Ricaurte, D., Richardson, M., Velez-Cortes, F., Blazejewski, T., Kaufman, A., Ronda, C., & Wang, H. H.
Affiliations
Columbia University (US)
Corresponding author
Wang, Harris H.
Venue
Nature Biotechnology
Published
2023-02-20
Volume
41
Issue
10
Pages
1424-1433
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W4321369770
Cited by
283
References
63
Citations by year
2026: 95 · 2025: 94 · 2024: 62 · 2023: 29 · 2017: 1 · 2014: 1
FWCI
24.73
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (MCB-2025515, DGE-1644869)
  • U.S. Department of Health & Human Services | National Institutes of Health (1R01AI132403, 1R21AI146817, T32GM007367)
  • United States Department of Defense | United States Navy | Office of Naval Research (N00014-18-1-2237, N00014-17-1-2353)
  • Burroughs Wellcome Fund (1016691)
  • Irma T. Hirschl Trust (NA)
  • Schaefer Research Award
  • Hertz Foundation (NA)
  • Junior Fellows Scholarship from the Simons Society of Fellows
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
Keywords
culturomics, colony morphology, fecal microbiota, microbial co-culture, Ruminococcaceae, Bacteroidaceae, Coriobacteriaceae, Bifidobacteriaceae, strain evolution, horizontal gene transfer
MeSH terms
Machine Learning, Automation, Bacteria, Humans, Genomics, Microbiota

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