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      Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary

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          Abstract

          Genome-wide association studies (GWAS) have become indispensable in human medicine and genomics, but very few have been carried out on bacteria. Here we introduce Scoary, an ultra-fast, easy-to-use, and widely applicable software tool that scores the components of the pan-genome for associations to observed phenotypic traits while accounting for population stratification, with minimal assumptions about evolutionary processes. We call our approach pan-GWAS to distinguish it from traditional, single nucleotide polymorphism (SNP)-based GWAS. Scoary is implemented in Python and is available under an open source GPLv3 license at https://github.com/AdmiralenOla/Scoary.

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          The online version of this article (doi:10.1186/s13059-016-1108-8) contains supplementary material, which is available to authorized users.

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          Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

          The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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            The microbial pan-genome.

            A decade after the beginning of the genomic era, the question of how genomics can describe a bacterial species has not been fully addressed. Experimental data have shown that in some species new genes are discovered even after sequencing the genomes of several strains. Mathematical modeling predicts that new genes will be discovered even after sequencing hundreds of genomes per species. Therefore, a bacterial species can be described by its pan-genome, which is composed of a "core genome" containing genes present in all strains, and a "dispensable genome" containing genes present in two or more strains and genes unique to single strains. Given that the number of unique genes is vast, the pan-genome of a bacterial species might be orders of magnitude larger than any single genome.
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              Adjusted P-Values for Simultaneous Inference

              S. Wright (1992)
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                Author and article information

                Contributors
                ola.brynildsrud@fhi.no
                jon.bohlin@fhi.no
                lonsch96@live.nl
                vegard.eldholm@fhi.no
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                25 November 2016
                25 November 2016
                2016
                : 17
                : 238
                Affiliations
                [1 ]Domain of Infectious Disease Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
                [2 ]Hanze University of Applied Sciences, Groningen, The Netherlands
                Author information
                http://orcid.org/0000-0001-7566-4133
                Article
                1108
                10.1186/s13059-016-1108-8
                5124306
                27887642
                ae48d508-f646-4a27-b953-11758a2b69a1
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 October 2016
                : 11 November 2016
                Categories
                Software
                Custom metadata
                © The Author(s) 2016

                Genetics
                pan-genome,accessory genome,annotation,prokaryote,genomics,whole-genome sequencing (wgs),next-generation sequencing (ngs),python,bacteria,genome-wide association studies (gwas),association

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