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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. (författare)
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Croucher, Nicholas J. (författare)
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Puranen, Santeri (författare)
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Chewapreecha, Claire (författare)
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Pesonen, Maiju (författare)
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Xu, Ying Ying (författare)
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Turner, Paul (författare)
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Harris, Simon R. (författare)
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Beres, Stephen B. (författare)
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Musser, James M. (författare)
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Parkhill, Julian (författare)
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Bentley, Stephen D. (författare)
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- Aurell, Erik (författare)
- KTH,Beräkningsbiologi, CB
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Corander, Jukka (författare)
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(creator_code:org_t)
- 2017-02-16
- 2017
- Engelska.
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:2
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Publikations- och innehållstyp
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- art (ämneskategori)
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- Av författaren/redakt...
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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
-
Xu, Ying Ying
-
visa fler...
-
Turner, Paul
-
Harris, Simon R.
-
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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visa färre...
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