ArticlePLoS genetics2014
Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 140 citations in OpenAlex.
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- Machine Learning for Antimicrobial Resistance Prediction: Current Practice, Limitations, and Clinical Perspective.Clinical microbiology reviews · 2022Review
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- Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes.eLife · 2022Article
- Auxotrophic and prototrophic conditional genetic networks reveal the rewiring of transcription factors in Escherichia coli.Nature communications · 2022Article
- Gradients in gene essentiality reshape antibacterial research.FEMS microbiology reviews · 2022Review
- Structure, Oligomerization and Activity Modulation in N-Ribohydrolases.International journal of molecular sciences · 2022Review
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- Exploring a Local Genetic Interaction Network Using Evolutionary Replay Experiments.Molecular biology and evolution · 2021Article
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6 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 6 institutions in 1 country.
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Abstract
Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI) screens can provide insights into the biological role(s) of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.
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