ArticleBMC genomics2016
Coupling high-throughput genetics with phylogenetic information reveals an epistatic interaction on the influenza A virus M segment.
Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Deep mutational scanning and CRISPR-engineered viruses: tools for evolutionary and functional genomics studies.mSphere · 2025Review
- Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing.eLife · 2021Article
- Applications of Deep Mutational Scanning in Virology.Viruses · 2021Review
- Adaptation of Oxford Nanopore technology for hepatitis C whole genome sequencing and identification of within-host viral variants.BMC genomics · 2021Article
- MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.Genome biology · 2019Article
- Contrasting selective patterns across the segmented genome of bluetongue virus in a global reassortment hotspot.Virus evolution · 2019Article
- Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance.Journal of virology · 2019Article
- Mutation and Epistasis in Influenza Virus Evolution.Viruses · 2018Review
- Mapping the Evolutionary Potential of RNA Viruses.Cell host & microbe · 2018Review
- Article
- Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody.Cell host & microbe · 2017Article
- Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2017Article
- Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.PLoS pathogens · 2017Article
- Complete mapping of viral escape from neutralizing antibodies.PLoS pathogens · 2017Article
- Article
- Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin.Viruses · 2016Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundEpistasis is one of the central themes in viral evolution due to its importance in drug resistance, immune escape, and interspecies transmission. However, there is a lack of experimental approach to systematically probe for epistatic residues.
resultsBy utilizing the information from natural occurring sequences and high-throughput genetics, this study established a novel strategy to identify epistatic residues. The rationale is that a substitution that is deleterious in one strain may be prevalent in nature due to the presence of a naturally occurring compensatory substitution. Here, high-throughput genetics was applied to influenza A virus M segment to systematically identify deleterious substitutions. Comparison with natural sequence variation showed that a deleterious substitution M1 Q214H was prevalent in circulating strains. A coevolution analysis was then performed and indicated that M1 residues 121, 207, 209, and 214 naturally coevolved as a group. Subsequently, we experimentally validated that M1 A209T was a compensatory substitution for M1 Q214H.
conclusionsThis work provided a proof-of-concept to identify epistatic residues by coupling high-throughput genetics with phylogenetic information. In particular, we were able to identify an epistatic interaction between M1 substitutions A209T and Q214H. This analytic strategy can potentially be adapted to study any protein of interest, provided that the information on natural sequence variants is available.
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