A phylogenetic method to perform genome-wide association studies in microbes that accounts for population structure and recombination
A phylogenetic method to perform genome-wide association studies in microbes that accounts for population structure and recombination
复制标题
一种在微生物中进行全基因组关联研究的系统发育方法，可解释种群结构和重组
DOI：
10.1101/140798
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Collins C
中科院分区：
文献类型：
--
作者：
Collins C
微生物的全基因组关联研究（GWAS）有可能极大地改善我们理解、管理和治疗传染病的方式。然而，迄今为止建立的微生物GWAS方法仍然不足以利用日益丰富的细菌和病毒基因序列数据。面对克隆群体结构和同源重组，现有的GWAS方法很难达到拒绝虚假发现所需的精度和检测微生物关联所需的能力。在本文中，我们介绍了一种新的系统发育的方法，已量身定制的微生物GWAS，这是适用于生物体范围从纯克隆频繁重组，二元和连续的表型。我们的方法是强大的人口结构和重组的混杂效应，同时保持高的统计能力来检测协会。通过应用到模拟数据的彻底测试为我们的方法的能力和特异性提供了强有力的支持，并展示了替代基于聚类和降维方法的优势。两个应用于脑膜炎奈瑟氏球菌disillustrate的多功能性和潜力，我们的方法，确认先前确定的青霉素耐药位点，并导致确定两个良好的特征和新的驱动因素的侵袭性疾病。我们的方法是作为一个名为treeWAS的开源R包实现的，它可以在https://github.com/caitiecollins/treeWAS上免费获得。
Genome-Wide Association Studies (GWAS) in microbial organisms have the potential to vastly improve the way we understand, manage, and treat infectious diseases. Yet, microbial GWAS methods established thus far remain insufficiently able to capitalise on the growing wealth of bacterial and viral genetic sequence data. Facing clonal population structure and homologous recombination, existing GWAS methods struggle to achieve both the precision necessary to reject spurious findings and the power required to detect associations in microbes. In this paper, we introduce a novel phylogenetic approach that has been tailor-made for microbial GWAS, which is applicable to organisms ranging from purely clonal to frequently recombining, and to both binary and continuous phenotypes. Our approach is robust to the confounding effects of both population structure and recombination, while maintaining high statistical power to detect associations. Thorough testing via application to simulated data provides strong support for the power and specificity of our approach and demonstrates the advantages offered over alternative cluster-based and dimension-reduction methods. Two applications toNeisseria meningitidisillustrate the versatility and potential of our method, confirming previously-identified penicillin resistance loci and resulting in the identification of both well-characterised and novel drivers of invasive disease. Our method is implemented as an open-source R package called treeWAS which is freely available at https://github.com/caitiecollins/treeWAS.
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DOI：
10.1042/cs20090513
发表时间：
2010-02-09
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Hill DJ;Griffiths NJ;Borodina E;Virji M
通讯作者：
Virji M
DOI：
10.1093/bioinformatics/bts396
发表时间：
2012-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cohen O;Ashkenazy H;Burstein D;Pupko T
通讯作者：
Pupko T
影响因子：
3.7
作者：
Power RA;Davaniah S;Derache A;Wilkinson E;Tanser F;Gupta RK;Pillay D;de Oliveira T
通讯作者：
de Oliveira T
影响因子：
3.5
作者：
Tian, Chao;Gregersen, Peter K.;Seldin, Michael F.
通讯作者：
Seldin, Michael F.
DOI：
10.1007/978-1-4939-6673-8_8
发表时间：
2017-01-01
期刊：
BACTERIAL PATHOGENESIS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Collins, Caitlin;Didelot, Xavier
通讯作者：
Didelot, Xavier