Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission.
Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission.
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DOI：
10.1099/mgen.0.000217
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发表时间：
2018-10
影响因子：
3.9
通讯作者：
Hanage WP
中科院分区：
文献类型：
--
作者：
Martin MA;Lee RS;Cowley LA;Gardy JL;Hanage WP
全基因组测序结合传统流行病学已被用于重建结核分枝杆菌在暴发期间的传播网络。鉴于其低突变率，结核分枝杆菌暴发中的遗传多样性可能极其有限--这使得很难准确确定谁将其传染给了谁。除了共识的SNPs(CSNPs)外，还提出了检测异质性等位基因(HSNPs)来提高分辨率。然而，很少有研究研究在检测这些hSNP时可能存在的偏向。在这里，我们分析了来自加拿大不列颠哥伦比亚省的25个样本的基因组序列数据。对标本进行测序，测序深度为112-296×。我们观察到在读取深度、碱基质量、链分布和可能的hSNP最初被发现的读取位置方面存在偏差，因此我们应用保守过滤器来减少假阳性。总体而言，观察到的2542个cSNP和63个HSNP基因座之间存在着系统发育上的一致性。此外，我们确定了仅由流行病学相关患者共享的hSNPs，支持将其用于传播推断。我们的结论是，hSNPs可能会增加传输网络的分辨率，特别是在总体遗传多样性较低的地方。
Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited – making it difficult to determine precisely who transmitted to whom. In addition to consensus SNPs (cSNPs), examining heterogeneous alleles (hSNPs) has been proposed to improve resolution. However, few studies have examined the potential biases in detecting these hSNPs. Here, we analysed genome sequence data from 25 specimens from British Columbia, Canada. Specimens were sequenced to a depth of 112–296×. We observed biases in read depth, base quality, strand distribution and read placement where possible hSNPs were initially identified, so we applied conservative filters to reduce false positives. Overall, there was phylogenetic concordance between the observed 2542 cSNP and 63 hSNP loci. Furthermore, we identified hSNPs shared exclusively by epidemiologically linked patients, supporting their use in transmission inferences. We conclude that hSNPs may add resolution to transmission networks, particularly where the overall genetic diversity is low.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1507071112
发表时间：
2015-11-03
影响因子：
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