Imperial College London
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DrNicholasCroucher

Faculty of Medicine, School of Public Health

Reader in Bacterial Genomics
 
 
 
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Contact

 

+44 (0)20 7594 3820n.croucher

 
 
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Location

 

1104Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Skwark:2017:10.1371/journal.pgen.1006508,
author = {Skwark, MJ and Croucher, NJ and Puranen, S and Chewapreecha, C and Pesonen, M and Xu, YY and Turner, P and Harris, SR and Beres, SB and Musser, JM and Parkhill, J and Bentley, SD and Aurell, E and Corander, J},
doi = {10.1371/journal.pgen.1006508},
journal = {PLoS Genetics},
title = {Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis},
url = {http://dx.doi.org/10.1371/journal.pgen.1006508},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 enhance
AU  - Skwark,MJ
AU  - Croucher,NJ
AU  - Puranen,S
AU  - Chewapreecha,C
AU  - Pesonen,M
AU  - Xu,YY
AU  - Turner,P
AU  - Harris,SR
AU  - Beres,SB
AU  - Musser,JM
AU  - Parkhill,J
AU  - Bentley,SD
AU  - Aurell,E
AU  - Corander,J
DO  - 10.1371/journal.pgen.1006508
PY  - 2017///
SN  - 1553-7390
TI  - Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1006508
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000395719300003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/55487
VL  - 13
ER  -
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