Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes.
Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes.
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DOI：
10.1038/ncomms12797
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发表时间：
2016-09-16
影响因子：
16.6
通讯作者：
Corander, Jukka
中科院分区：
文献类型：
--
作者：
Lees, John A.;Vehkala, Minna;Valimaki, Niko;Harris, Simon R.;Chewapreecha, Claire;Croucher, Nicholas J.;Marttinen, Pekka;Davies, Mark R.;Steer, Andrew C.;Tong, Steven Y. C.;Honkela, Antti;Parkhill, Julian;Bentley, Stephen D.;Corander, Jukka
细菌基因组在基因含量和基因序列方面差异很大。这种可塑性阻碍了使用传统的基于snp的方法来识别与表型变异的所有遗传关联。在这里，我们介绍了一种计算可扩展和广泛适用的统计方法（SEER），用于识别在感兴趣的表型中显着丰富的序列元素。SEER通过使用分布式字符串挖掘算法计数变长k-mers，适用于数万个基因组。为关联分析提供了健壮的选项，也纠正了细菌的克隆群体结构。利用主要人类病原体肺炎链球菌和化脓性链球菌的大量基因组，SEER确定了几种抗生素的相关先前表征的耐药决定因素，并发现了与化脓性链球菌侵袭性相关的潜在新因素。因此，我们证明了我们的方法可以回答重要的生物学和医学相关问题。细菌基因组的可塑性和克隆群体结构阻碍了传统的基于snp的遗传关联研究。在这里，Corander和他的同事提出了一种方法来识别在感兴趣的表型中丰富的变长序列元素，并证明了它在人类病原体中的应用。
Bacterial genomes vary extensively in terms of both gene content and gene sequence. This plasticity hampers the use of traditional SNP-based methods for identifying all genetic associations with phenotypic variation. Here we introduce a computationally scalable and widely applicable statistical method (SEER) for the identification of sequence elements that are significantly enriched in a phenotype of interest. SEER is applicable to tens of thousands of genomes by counting variable-length k-mers using a distributed string-mining algorithm. Robust options are provided for association analysis that also correct for the clonal population structure of bacteria. Using large collections of genomes of the major human pathogens Streptococcus pneumoniae and Streptococcus pyogenes, SEER identifies relevant previously characterized resistance determinants for several antibiotics and discovers potential novel factors related to the invasiveness of S. pyogenes. We thus demonstrate that our method can answer important biologically and medically relevant questions. Plasticity and clonal population structure in bacterial genomes can hinder traditional SNP-based genetic association studies. Here, Corander and colleagues present a method to identify variable-length sequence elements enriched in a phenotype of interest, and demonstrate its use in human pathogens.
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影响因子：
4.5
作者：
Chewapreecha C;Marttinen P;Croucher NJ;Salter SJ;Harris SR;Mather AE;Hanage WP;Goldblatt D;Nosten FH;Turner C;Turner P;Bentley SD;Parkhill J
通讯作者：
Parkhill J
影响因子：
10.7
作者：
Kosiol, Carolin;Holmes, Ian;Goldman, Nick
通讯作者：
Goldman, Nick
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng
影响因子：
2
作者：
Heinze, G;Schemper, M
通讯作者：
Schemper, M