Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis
Publication Date
February 16, 2017
Authors
Marcin J. Skwark, Nicholas J. Croucher, Santeri Puranen, Claire Chewapreecha, et al
Volume
13
Issue
2
Pages
e1006508
DOI
https://dx.plos.org/10.1371/journal.pgen.1006508
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1006508
Scopus
85014119857
Mendeley
http://www.mendeley.com/research/interacting-networks-resistance-virulence-core-machinery-genes-identified-genomewide-epistasis-analy
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Mendeley | Further Information

{"title"=>"Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Marcin J.", "last_name"=>"Skwark", "scopus_author_id"=>"25824446200"}, {"first_name"=>"Nicholas J.", "last_name"=>"Croucher", "scopus_author_id"=>"26326753500"}, {"first_name"=>"Santeri", "last_name"=>"Puranen", "scopus_author_id"=>"6504216128"}, {"first_name"=>"Claire", "last_name"=>"Chewapreecha", "scopus_author_id"=>"55249688500"}, {"first_name"=>"Maiju", "last_name"=>"Pesonen", "scopus_author_id"=>"57193453845"}, {"first_name"=>"Ying Ying", "last_name"=>"Xu", "scopus_author_id"=>"57193453488"}, {"first_name"=>"Paul", "last_name"=>"Turner", "scopus_author_id"=>"37011586200"}, {"first_name"=>"Simon R.", "last_name"=>"Harris", "scopus_author_id"=>"35277976300"}, {"first_name"=>"Stephen B.", "last_name"=>"Beres", "scopus_author_id"=>"6602638769"}, {"first_name"=>"James M.", "last_name"=>"Musser", "scopus_author_id"=>"7103224550"}, {"first_name"=>"Julian", "last_name"=>"Parkhill", "scopus_author_id"=>"7005397039"}, {"first_name"=>"Stephen D.", "last_name"=>"Bentley", "scopus_author_id"=>"7102548116"}, {"first_name"=>"Erik", "last_name"=>"Aurell", "scopus_author_id"=>"55884846500"}, {"first_name"=>"Jukka", "last_name"=>"Corander", "scopus_author_id"=>"6603490546"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-85014119857", "isbn"=>"1111111111", "doi"=>"10.1371/journal.pgen.1006508", "pui"=>"614650961", "sgr"=>"85014119857", "issn"=>"15537404", "pmid"=>"28207813"}, "id"=>"566baa60-3c16-367c-9365-6e762d540ae7", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/interacting-networks-resistance-virulence-core-machinery-genes-identified-genomewide-epistasis-analy", "reader_count"=>77, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>18, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>5, "Other"=>1, "Student > Master"=>9, "Student > Bachelor"=>8, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>18, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>5, "Other"=>1, "Student > Master"=>9, "Student > Bachelor"=>8, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Engineering"=>3, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>38, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Computer Science"=>3, "Immunology and Microbiology"=>8}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>38}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "China"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>3}

Scopus | Further Information

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