Mutant phenotypes for thousands of bacterial genes of unknown function
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Abstract
One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.
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Recent technologies for bacterial phenotyping and phage receptor identification enable predictive modeling.
“Recent technologies for bacterial phenotyping and phage receptor identification enable predictive modeling [90,151–156]”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [155]
The section ‘Conserved phenotypes are accurate predictors of protein function’ describes using bacterial mutant phenotypes to predict protein functions, supporting the phenotyping part of the sentence. The cited paper does not address phage receptor identification or its contribution to predictive modeling; the full sentence is therefore only partly supported by this source. No page number is available in our copy. (LLM, conf=0.83)
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Self-citation
- Authors
- Price, M. N., Wetmore, K. M., Waters, R. J., Callaghan, M., Ray, J., Liu, H., Kuehl, J. V., Melnyk, R. A., Lamson, J. S., Suh, Y., Carlson, H. K., Esquivel, Z., Sadeeshkumar, H., Chakraborty, R., Zane, G. M., Rubin, B. E., Wall, J. D., Visel, A., Bristow, J., Blow, M. J., Arkin, A. P., & Deutschbauer, A. M.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of Missouri (US)
- University of California San Diego (US)
- Corresponding author
- Blow, Matthew J.
- Arkin, Adam P.
- Deutschbauer, Adam M.
- ORCID
- Venue
- Nature
- Published
- 2018-05-16
- Volume
- 557
- Issue
- 7706
- Pages
- 503-509
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2804515387
- Cited by
- 576
- References
- 4
- Citations by year
- 2026: 59 · 2025: 73 · 2024: 65 · 2023: 72 · 2022: 62 · 2021: 75 · 2020: 64 · 2019: 60 · 2018: 32 · 2017: 12 · 2014: 1
- FWCI
- 20.55
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
- Joint Genome Institute (AC02-05CH11231, DE–AC02–05CH11231)
- National Institutes of Health (1s10od018174-01, DE-AC02–05CH11231)
- Directorate for Biological Sciences
- Office of Science (DEAC02–05CH11231, AC02-05CH11231, DE-AC02, 05CH11231)
- University of California, Davis
- National Center for Research Resources (S10RR029668, S10RR027303)
- Biological and Environmental Research (05CH11231, DE-AC02 − 05CH11231, AC02-05CH11231)
- Laboratory Directed Research and Development (DEAC02-05CH11231)
- Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- gene function annotation, gene function prediction, DNA repair proteins, comparative genomics, microbial genetics, transporters
- MeSH terms
- Bacteria, Bacterial Proteins, DNA Repair, Genes, Bacterial, Mutation, Phenotype, Genome, Bacterial, Conserved Sequence, Uncertainty, Mutant Proteins, Genetic Fitness, Molecular Sequence Annotation
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