ArticleNature microbiology2019
Genome-wide discovery of epistatic loci affecting antibiotic resistance in Neisseria gonorrhoeae using evolutionary couplings.
Article in Nature microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Epistasis and co-adaptation in bacterial genome evolution.Nature reviews. Genetics · 2026Review
- Gonorrhea Management in High-, Limited- and No-Resource Settings: Implications in the Context of Antimicrobial Resistance.International journal of dermatology · 2026Review
- A bacterial ecocline in Klebsiella pneumoniae may explain its backboned phylogeny.PLoS biology · 2026Article
- Genome co-adaptation and the evolution of methicillin resistant Staphylococcus aureus.Genome biology · 2026Article
- aurora: a machine learning gwas tool for analyzing microbial habitat adaptation.Genome biology · 2025Article
- Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution.mSystems · 2025Review
- Detecting co-selection through excess linkage disequilibrium in bacterial genomes.NAR genomics and bioinformatics · 2024Article
- Global epistasis in plasmid-mediated antimicrobial resistance.Molecular systems biology · 2024Review
- Genome-Wide Association Studies (GWAS) Approaches for the Detection of Genetic Variants Associated with Antibiotic Resistance: A Systematic Review.Microorganisms · 2023Review
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot.Nature communications · 2023Article
- Inferring the heritability of bacterial traits in the era of machine learning.Bioinformatics advances · 2023Review
- Identification of potential pathogenic targets and survival strategies ofFrontiers in cellular and infection microbiology · 2023Article
- Mycobacterium abscessus pathogenesis identified by phenogenomic analyses.Nature microbiology · 2022Article
- Bioinformatics tools used for whole-genome sequencing analysis of Neisseria gonorrhoeae: a literature review.Briefings in functional genomics · 2022Review
- Inverse Potts model improves accuracy of phylogenetic profiling.Bioinformatics (Oxford, England) · 2022Article
- Co-evolutionary Signals Identify Burkholderia pseudomallei Survival Strategies in a Hostile Environment.Molecular biology and evolution · 2022Article
- Robustness of Phylogenetic Inference to Model Misspecification Caused by Pairwise Epistasis.Molecular biology and evolution · 2021Article
- Forest and Trees: Exploring Bacterial Virulence with Genome-wide Association Studies and Machine Learning.Trends in microbiology · 2021Review
- Article
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Authors and funding
5 authors.
Funding
Abstract
Genome analysis should allow the discovery of interdependent loci that together cause antibiotic resistance. In practice, however, the vast number of possible epistatic interactions erodes statistical power. Here, we extend an approach that has been successfully used to identify epistatic residues in proteins to infer genomic loci that are strongly coupled. This approach reduces the number of tests required for an epistatic genome-wide association study of antibiotic resistance and increases the likelihood of identifying causal epistasis. We discovered 38 loci and 240 epistatic pairs that influence the minimum inhibitory concentrations of 5 different antibiotics in 1,102 isolates of Neisseria gonorrhoeae that were confirmed in a second dataset of 495 isolates. Many known resistance-affecting loci were recovered; however, the majority of associations occurred in unreported genes, such as murE. About half of the discovered epistasis involved at least one locus previously associated with antibiotic resistance, including interactions between gyrA and parC. Still, many combinations involved unreported loci and genes. While most variation in minimum inhibitory concentrations could be explained by identified loci, epistasis substantially increased explained phenotypic variance. Our work provides a systematic identification of epistasis affecting antibiotic resistance in N. gonorrhoeae and a generalizable approach for epistatic genome-wide association studies.
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