Analysis of 3.5 million SARS-CoV-2 sequences reveals unique mutational trends with consistent nucleotide and codon frequencies.
Analysis of 3.5 million SARS-CoV-2 sequences reveals unique mutational trends with consistent nucleotide and codon frequencies.
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DOI：
10.1186/s12985-023-01982-8
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发表时间：
2023-02-17
期刊：
影响因子：
4.8
通讯作者：
Kimchi-Sarfaty, Chava
中科院分区：
文献类型：
--
作者：
Fumagalli, Sarah E.;Padhiar, Nigam H.;Meyer, Douglas;Katneni, Upendra;Bar, Haim;DiCuccio, Michael;Komar, Anton A.;Kimchi-Sarfaty, Chava
关键词：
自SARS-CoV-2大流行开始以来，已经进行了生物信息学分析以了解病毒的核苷酸和同义密码子使用特征和突变模式。然而，相对而言，很少有人尝试对相当大的病毒基因组队列进行这种分析，同时组织大量可用的序列数据进行逐月分析，以观察随时间的变化。在这里，我们的目的是进行序列组成和突变分析的SARS-CoV-2，分离序列的基因，进化枝，和时间点，并对比突变谱的SARS-CoV-2的其他可比的RNA病毒。使用从GISAID数据库下载的超过350万个序列的清洁、过滤和预比对数据集，我们计算了核苷酸和密码子使用统计数据，包括计算相对同义密码子使用值。然后，我们计算了密码子适应指数（CAI）的变化和非同义/同义突变比（dN/dS）随着时间的推移，我们的数据集。最后，我们收集了SARS-CoV-2和其他类似RNA病毒突变类型的信息，并生成了热图，显示了刺突序列沿着高熵位置的密码子和核苷酸组成。我们发现，核苷酸和密码子使用的指标保持相对一致的32个月的跨度，虽然有显着差异的进化枝内每个基因在不同的时间点。CAI和dN/dS值在不同时间点和不同基因之间变化很大，刺突基因平均显示最高的CAI和dN/dS值。突变分析表明，SARS-CoV-2 Spike的非同义突变比例高于其他RNA病毒中的类似基因，非同义突变数量超过同义突变数量高达20：1。然而，在几个特定的位置，同义突变占压倒性优势。我们的多方面分析涵盖了SARS-CoV-2的组成和突变特征，为SARS-CoV-2随时间的核苷酸频率和密码子使用异质性以及与其他RNA病毒相比独特的突变谱提供了有价值的见解。在线版本包含补充材料，可通过10.1186/s12985-023-01982-8获得。
Since the onset of the SARS-CoV-2 pandemic, bioinformatic analyses have been performed to understand the nucleotide and synonymous codon usage features and mutational patterns of the virus. However, comparatively few have attempted to perform such analyses on a considerably large cohort of viral genomes while organizing the plethora of available sequence data for a month-by-month analysis to observe changes over time. Here, we aimed to perform sequence composition and mutation analysis of SARS-CoV-2, separating sequences by gene, clade, and timepoints, and contrast the mutational profile of SARS-CoV-2 to other comparable RNA viruses. Using a cleaned, filtered, and pre-aligned dataset of over 3.5 million sequences downloaded from the GISAID database, we computed nucleotide and codon usage statistics, including calculation of relative synonymous codon usage values. We then calculated codon adaptation index (CAI) changes and a nonsynonymous/synonymous mutation ratio (dN/dS) over time for our dataset. Finally, we compiled information on the types of mutations occurring for SARS-CoV-2 and other comparable RNA viruses, and generated heatmaps showing codon and nucleotide composition at high entropy positions along the Spike sequence. We show that nucleotide and codon usage metrics remain relatively consistent over the 32-month span, though there are significant differences between clades within each gene at various timepoints. CAI and dN/dS values vary substantially between different timepoints and different genes, with Spike gene on average showing both the highest CAI and dN/dS values. Mutational analysis showed that SARS-CoV-2 Spike has a higher proportion of nonsynonymous mutations than analogous genes in other RNA viruses, with nonsynonymous mutations outnumbering synonymous ones by up to 20:1. However, at several specific positions, synonymous mutations were overwhelmingly predominant. Our multifaceted analysis covering both the composition and mutation signature of SARS-CoV-2 gives valuable insight into the nucleotide frequency and codon usage heterogeneity of SARS-CoV-2 over time, and its unique mutational profile compared to other RNA viruses. The online version contains supplementary material available at 10.1186/s12985-023-01982-8.
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影响因子：
4.4
作者：
Das JK;Roy S
通讯作者：
Roy S
DOI：
10.1074/jbc.m110.162685
发表时间：
2011-01-21
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
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Pyle AM
影响因子：
5.8
作者：
Du L;Yang Y;Zhou Y;Lu L;Li F;Jiang S
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Jiang S
影响因子：
2.4
作者：
Zhang Y;Jin X;Wang H;Miao Y;Yang X;Jiang W;Yin B
通讯作者：
Yin B