Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
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DOI：
10.7554/elife.53245
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发表时间：
2020-02-04
期刊：
影响因子：
7.7
通讯作者：
Hanage, William P.
中科院分区：
文献类型：
--
作者：
Lee, Robyn S.;Proulx, Jean-Francois;Hanage, William P.
肺结核对加拿大因纽特人的影响尤为严重。为了解决这个问题，我们必须了解这一人群的传播动态。我们使用来自北极的一次特征明确的疫情（2011-2012年，50例），调查与标准测序相比，“深度”测序是否可以提供额外的分辨率。将样品测序至类似于500- 1000 x，并将读数与PacBio SMRT测序产生的新的局部参考基因组进行比对。在基因组中鉴定和比较共有和异质变体。与之前使用类似于50倍深度的基因组分析相比，深度测序使我们能够确定一种新的超级传播者，该超级传播者可能在疫情期间传播了多达17例其他病例（占当年剩余病例的35%）。越来越明显的是，宿主内多样性应纳入传播分析;深度测序可能有助于更准确地检测超级传播者和传播集群。这不仅对结核病有影响，而且对所有传播的基因组研究都有影响--无论病原体是什么。
Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether 'deep' sequencing can provide additional resolution compared to standard sequencing, using a well-characterized outbreak from the Arctic (2011-2012, 50 cases). Samples were sequenced to similar to 500-1000x and reads were aligned to a novel local reference genome generated with PacBio SMRT sequencing. Consensus and heterogeneous variants were identified and compared across genomes. In contrast with previous genomic analyses using similar to 50x depth, deep sequencing allowed us to identify a novel super-spreader who likely transmitted to up to 17 other cases during the outbreak (35% of the remaining cases that year). It is increasingly evident that within-host diversity should be incorporated into transmission analyses; deep sequencing may facilitate more accurate detection of super-spreaders and transmission clusters. This has implications not only for TB, but all genomic studies of transmission - regardless of pathogen.