Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies.
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DOI：
10.1186/s13073-021-00882-2
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发表时间：
2021-04-19
期刊：
影响因子：
12.3
通讯作者：
Ji HP
中科院分区：
文献类型：
--
作者：
Lau BT;Pavlichin D;Hooker AC;Almeda A;Shin G;Chen J;Sahoo MK;Huang CH;Pinsky BA;Lee HJ;Ji HP
SARS-CoV-2的基因组在病毒复制过程中由于RNA依赖性RNA聚合酶产生的错误而容易发生突变。这些突变使SARS-CoV-2能够进化成新的毒株。病毒准种来自个体患者发生的从头突变。结合起来，这些病毒突变集提供了不同的遗传指纹，揭示了传播模式，并在接触者追踪中具有实用性。利用数千个测序的SARS-CoV-2基因组，我们进行了病毒泛基因组分析，以确定保守的基因组序列。我们使用了一种快速高效的计算方法，该方法依赖于k-mers，即短序列，而不是传统的序列比对。使用这种方法，我们注释了与特定毒株相关的病毒突变特征。基于这些高度保守的病毒序列，我们开发了一种快速且高度可扩展的靶向测序检测方法，以识别突变，检测准种变体，并识别患者的突变特征。这些结果与泛基因组遗传指纹进行了比较。我们为数千个SARS-CoV-2基因组建立了一个k-mer索引，并在数千个病毒基因组中确定了保守的基因组区域和突变景观。我们描绘了跨越常见遗传指纹（病毒组装中的突变组合）和仅出现在少数患者中的突变组合的突变谱。我们通过从保守的病毒基因组区域选择引物以侧翼频繁突变来开发靶向测序测定。使用100个SARS-CoV-2临床样本的队列，我们确定了遗传指纹，包括在人群中观察到的菌株特异性突变和定位于个体感染的从头准种突变。我们比较了进行分析的病毒样本的突变谱与泛基因组的特征。我们对病毒突变谱进行了分析，为遗传指纹提供了基础。我们的研究将泛基因组分析与靶向深度测序的SARS-CoV-2临床样本联系起来。我们确定了个体患者中发生的准种突变，并确定了与70，000多个其他菌株相比的一般患病率。对这些遗传指纹的分析可以提供一种进行分子接触追踪的方法。
The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contact tracing. Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies variants, and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints. We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and a combination of mutations that appear in only a small number of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of 100 SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome. We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients and determined their general prevalence when compared to over 70,000 other strains. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.
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使用下一代靶向重新取样对稀有突变的超敏感检测。
影响因子：
14.9
作者：
Flaherty P;Natsoulis G;Muralidharan O;Winters M;Buenrostro J;Bell J;Brown S;Holodniy M;Zhang N;Ji HP
通讯作者：
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Paten B
影响因子：
64.8
作者：
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通讯作者：
MacArthur, Daniel G
影响因子：
3
作者：
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通讯作者：
Sonnhammer EL
影响因子：
30.5
作者：
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通讯作者：
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