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Interacting network...
Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
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Skwark, Marcin J. (author)
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Croucher, Nicholas J. (author)
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Puranen, Santeri (author)
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Chewapreecha, Claire (author)
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Pesonen, Maiju (author)
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Xu, Ying Ying (author)
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Turner, Paul (author)
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Harris, Simon R. (author)
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Beres, Stephen B. (author)
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Musser, James M. (author)
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Parkhill, Julian (author)
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Bentley, Stephen D. (author)
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- Aurell, Erik (author)
- KTH,Beräkningsbiologi, CB
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Corander, Jukka (author)
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(creator_code:org_t)
- 2017-02-16
- 2017
- English.
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:2
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https://doi.org/10.1...
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https://journals.plo...
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Skwark, Marcin J ...
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Croucher, Nichol ...
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Puranen, Santeri
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Chewapreecha, Cl ...
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Pesonen, Maiju
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Xu, Ying Ying
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show more...
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Turner, Paul
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Harris, Simon R.
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Beres, Stephen B ...
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Musser, James M.
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Parkhill, Julian
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Bentley, Stephen ...
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Aurell, Erik
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Corander, Jukka
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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PLOS Genetics
- By the university
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Royal Institute of Technology