Publication: Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
Issued Date
2017-02-01
Resource Type
ISSN
15537404
15537390
15537390
Other identifier(s)
2-s2.0-85014119857
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS Genetics. Vol.13, No.2 (2017)
Suggested Citation
Marcin J. Skwark, Nicholas J. Croucher, Santeri Puranen, Claire Chewapreecha, Maiju Pesonen, Ying Ying Xu, Paul Turner, Simon R. Harris, Stephen B. Beres, James M. Musser, Julian Parkhill, Stephen D. Bentley, Erik Aurell, Jukka Corander Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis. PLoS Genetics. Vol.13, No.2 (2017). doi:10.1371/journal.pgen.1006508 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41534
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
Other Contributor(s)
Vanderbilt University
Imperial College London
Aalto University
University of Cambridge
Mahidol University
Nuffield Department of Clinical Medicine
Wellcome Trust Sanger Institute
Methodist Hospital Houston
Weill Cornell Medical College
The Royal Institute of Technology (KTH)
Institute of Theoretical Physics Chinese Academy of Sciences
Helsingin Yliopisto
Universitetet i Oslo
Imperial College London
Aalto University
University of Cambridge
Mahidol University
Nuffield Department of Clinical Medicine
Wellcome Trust Sanger Institute
Methodist Hospital Houston
Weill Cornell Medical College
The Royal Institute of Technology (KTH)
Institute of Theoretical Physics Chinese Academy of Sciences
Helsingin Yliopisto
Universitetet i Oslo
Abstract
© 2017 Skwark et al. Recent advances in the scale and diversity of population genomic datasets for bacteria now provide the potential for genome-wide patterns of co-evolution to be studied at the resolution of individual bases. Here we describe a new statistical method, genomeDCA, which uses recent advances in computational structural biology to identify the polymorphic loci under the strongest co-evolutionary pressures. We apply genomeDCA to two large population data sets representing the major human pathogens Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A Streptococcus). For pneumococcus we identified 5,199 putative epistatic interactions between 1,936 sites. Over three-quarters of the links were between sites within the pbp2x, pbp1a and pbp2b genes, the sequences of which are critical in determining non-susceptibility to beta-lactam antibiotics. A network-based analysis found these genes were also coupled to that encoding dihydrofolate reductase, changes to which underlie trimethoprim resistance. Distinct from these antibiotic resistance genes, a large network component of 384 protein coding sequences encompassed many genes critical in basic cellular functions, while another distinct component included genes associated with virulence. The group A Streptococcus (GAS) data set population represents a clonal population with relatively little genetic variation and a high level of linkage disequilibrium across the genome. Despite this, we were able to pinpoint two RNA pseudouridine synthases, which were each strongly linked to a separate set of loci across the chromosome, representing biologically plausible targets of co-selection. The population genomic analysis method applied here identifies statistically significantly co-evolving locus pairs, potentially arising from fitness selection interdependence reflecting underlying protein-protein interactions, or genes whose product activities contribute to the same phenotype. This discovery approach greatly enhances the future potential of epistasis analysis for systems biology, and can complement genome-wide association studies as a means of formulating hypotheses for targeted experimental work.