ITP OpenIR  > 理论物理所2017年知识产出
Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
Skwark, MJ; Croucher, NJ; Puranen, S; Chewapreecha, C; Pesonen, M; Xu, YY; Turner, P; Harris, SR; Beres, SB; Musser, JM; Parkhill, J; Bentley, SD; Aurell, E; Corander, J; Corander, J (reprint author), Wellcome Trust Sanger Inst, Pathogen Gen, Cambridge, England.; Aurell, E (reprint author), KTH Royal Inst Technol, Dept Computat Biol, Stockholm, Sweden.; Aurell, E (reprint author), Aalto Univ, Dept Appl Phys & Comp Sci, Espoo, Finland.; Aurell, E (reprint author), Chinese Acad Sci, Inst Theoret Phys, Beijing, Peoples R China.; Corander, J (reprint author), Univ Helsinki, Dept Math & Stat, Helsinki, Finland.; Corander, J (reprint author), Univ Oslo, Dept Biostat, Oslo, Norway.; Corander, J (reprint author), Univ Cambridge, Dept Vet Med, Cambridge, England.
2017
发表期刊PLOS GENETICS
卷号13期号:2页码:e1006508
文章类型Article
摘要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.
学科领域Genetics & Heredity
资助者COIN Centre of Excellence, Academy of Finland, Finland [251170] ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; Wellcome Trust ; Wellcome Trust ; Royal Society [104169/Z/14/Z] ; Royal Society [104169/Z/14/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Fondren Foundation ; Fondren Foundation ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Sir Henry Dale Fellowship ; Sir Henry Dale Fellowship ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; Wellcome Trust ; Wellcome Trust ; Royal Society [104169/Z/14/Z] ; Royal Society [104169/Z/14/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Fondren Foundation ; Fondren Foundation ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Sir Henry Dale Fellowship ; Sir Henry Dale Fellowship
DOIhttp://dx.doi.org/10.1371/journal.pgen.1006508
关键词[WOS]DIRECT-COUPLING ANALYSIS ; STREPTOCOCCUS-PNEUMONIAE ; PENICILLIN RESISTANCE ; STATISTICAL-METHODS ; CONTACT PREDICTION ; RESIDUE CONTACTS ; EVOLUTION ; PROTEINS ; ASSOCIATION ; COEVOLUTION
语种英语
资助者COIN Centre of Excellence, Academy of Finland, Finland [251170] ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; Wellcome Trust ; Wellcome Trust ; Royal Society [104169/Z/14/Z] ; Royal Society [104169/Z/14/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Fondren Foundation ; Fondren Foundation ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Sir Henry Dale Fellowship ; Sir Henry Dale Fellowship ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; COIN Centre of Excellence, Academy of Finland, Finland [251170] ; Wellcome Trust ; Wellcome Trust ; Royal Society [104169/Z/14/Z] ; Royal Society [104169/Z/14/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Sir Henry Wellcome Postdoctoral Fellowship [107276/Z/15/Z] ; Fondren Foundation ; Fondren Foundation ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Chinese Academy of Sciences CAS President's International Fellowship Initiative (PIFI) [2016VMA002] ; Sir Henry Dale Fellowship ; Sir Henry Dale Fellowship
WOS类目Genetics & Heredity
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文献类型期刊论文
条目标识符http://ir.itp.ac.cn/handle/311006/22136
专题理论物理所2017年知识产出
通讯作者Corander, J (reprint author), Wellcome Trust Sanger Inst, Pathogen Gen, Cambridge, England.; Aurell, E (reprint author), KTH Royal Inst Technol, Dept Computat Biol, Stockholm, Sweden.; Aurell, E (reprint author), Aalto Univ, Dept Appl Phys & Comp Sci, Espoo, Finland.; Aurell, E (reprint author), Chinese Acad Sci, Inst Theoret Phys, Beijing, Peoples R China.; Corander, J (reprint author), Univ Helsinki, Dept Math & Stat, Helsinki, Finland.; Corander, J (reprint author), Univ Oslo, Dept Biostat, Oslo, Norway.; Corander, J (reprint author), Univ Cambridge, Dept Vet Med, Cambridge, England.
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Skwark, MJ,Croucher, NJ,Puranen, S,et al. Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis[J]. PLOS GENETICS,2017,13(2):e1006508.
APA Skwark, MJ.,Croucher, NJ.,Puranen, S.,Chewapreecha, C.,Pesonen, M.,...&Corander, J .(2017).Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis.PLOS GENETICS,13(2),e1006508.
MLA Skwark, MJ,et al."Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis".PLOS GENETICS 13.2(2017):e1006508.
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