Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data.
Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data.
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DOI：
10.1186/1471-2334-13-110
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发表时间：
2013-02-27
影响因子：
3.7
通讯作者：
van Soolingen D
中科院分区：
文献类型：
--
作者：
Bryant JM;Schürch AC;van Deutekom H;Harris SR;de Beer JL;de Jager V;Kremer K;van Hijum SA;Siezen RJ;Borgdorff M;Bentley SD;Parkhill J;van Soolingen D
结核分枝杆菌的特征在于有限的基因组多样性，这使得全基因组测序的应用对于临床和流行病学调查特别有吸引力。然而，为了有信心地推断传播事件，需要准确了解相关时间尺度上基因组的变化率。我们试图通过对199株来自荷兰近16年来收集的流行病学相关结核病病例的分离株进行测序来估计分子钟。多项分析支持每年每个基因组约0.3个SNP的平均突变率。然而，所有的分析都揭示了围绕这个平均值的非常高的变化程度，使得流行病学提出的联系的确认和新联系的推断变得困难。尽管如此，在某些情况下，其他菌株的系统发育背景提供了证据，支持可靠地排除先前推断的流行病学联系。对分子钟的深入分析表明，它在短时间尺度上是缓慢和可变的，这限制了它在传输研究中的有用性。然而，全基因组测序的上级分辨率可以提供系统发育背景，以允许有信心地排除先前通过传统DNA指纹技术和流行病学聚类调查推断的可能的传播事件。尽管即使在全基因组水平上变异的产生也很缓慢，但我们得出的结论是，常规全基因组测序将极大地受益于结核病传播的研究。
Mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. However, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required. We attempted to estimate a molecular clock by sequencing 199 isolates from epidemiologically linked tuberculosis cases, collected in the Netherlands spanning almost 16 years. Multiple analyses support an average mutation rate of ~0.3 SNPs per genome per year. However, all analyses revealed a very high degree of variation around this mean, making the confirmation of links proposed by epidemiology, and inference of novel links, difficult. Despite this, in some cases, the phylogenetic context of other strains provided evidence supporting the confident exclusion of previously inferred epidemiological links. This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies. However, the superior resolution of whole genome sequencing can provide the phylogenetic context to allow the confident exclusion of possible transmission events previously inferred via traditional DNA fingerprinting techniques and epidemiological cluster investigation. Despite the slow generation of variation even at the whole genome level we conclude that the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.
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影响因子：
30.8
作者：
Comas, Inaki;Borrell, Sonia;Roetzer, Andreas;Rose, Graham;Malla, Bijaya;Kato-Maeda, Midori;Galagan, James;Niemann, Stefan;Gagneux, Sebastien
通讯作者：
Gagneux, Sebastien
影响因子：
7
作者：
Namouchi, Amine;Didelot, Xavier;Rocha, Eduardo P. C.
通讯作者：
Rocha, Eduardo P. C.
影响因子：
9.4
作者：
de Beer, Jessica L.;Kremer, Kristin;van Soolingen, Dick
通讯作者：
van Soolingen, Dick
影响因子：
9.4
作者：
Kamerbeek, J;Schouls, L;vanEmbden, J
通讯作者：
vanEmbden, J
影响因子：
4.9
作者：
TAKIFF, HE;SALAZAR, L;TELENTI, A
通讯作者：
TELENTI, A