Analysis of SARS-CoV-2 known and novel subgenomic mRNAs in cell culture, animal model, and clinical samples using LeTRS, a bioinformatic tool to identify unique sequence identifiers.
Analysis of SARS-CoV-2 known and novel subgenomic mRNAs in cell culture, animal model, and clinical samples using LeTRS, a bioinformatic tool to identify unique sequence identifiers.
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使用LETRS（一种生物信息学工具）分析细胞培养，动物模型和临床样品中SARS-COV-2已知和新型亚基因组mRNA，以识别唯一的序列标识符。
DOI：
10.1093/gigascience/giac045
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发表时间：
2022-05-26
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）对病毒亚基因组mRNA（sgmRNAs）的转录具有复杂的策略，其是核酸诊断的靶标。这些sgmRNA中的每一个都具有独特的5′序列，即前导序列-转录调控序列基因连接（前导序列-TRS连接），其可以使用测序来鉴定。高分辨率测序已被用于研究SARS-CoV-2的生物学以及细胞培养和动物模型以及临床样本中的宿主反应。LeTRS是一种生物信息学工具，用于鉴定前导序列-TRS连接，并可用作定量sgmRNA的替代物，以了解病毒生物学。LeTRS很容易适用于其他冠状病毒，如中东呼吸综合征冠状病毒或未来新发现的冠状病毒。LeTRS在已发表的数据集和来自患者的新型临床样本以及来自2019年冠状病毒病动物模型的纵向样本上进行了测试。LeTRS鉴定了已知的前导-TRS连接，并鉴定了在不同哺乳动物物种中常见的推定的新型sgmRNA。这可能表明了一种进化机制，在这种机制中，转录的可塑性产生了新的开放阅读框架，然后可以受到选择压力。数据表明在两种不同的动物模型中sgmRNA的多相丰度。这概括了在感染的早期点而不是在晚期点在细胞中观察到的相对sgmRNA丰度。这种模式反映在一些人类鼻咽样本中，因此对传播模型和基于核酸的诊断具有影响。LeTRS提供了来自测序数据的sgmRNA丰度的定量测量。这可用于评估临床和非临床样本中SARS-CoV-2（或其他冠状病毒）的生物学，特别是评估可能影响病毒RNA合成的不同变体和医学对策。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgmRNAs has a unique 5′ sequence, the leader–transcriptional regulatory sequence gene junction (leader–TRS junction), that can be identified using sequencing. High-resolution sequencing has been used to investigate the biology of SARS-CoV-2 and the host response in cell culture and animal models and from clinical samples. LeTRS, a bioinformatics tool, was developed to identify leader–TRS junctions and can be used as a proxy to quantify sgmRNAs for understanding virus biology. LeTRS is readily adaptable for other coronaviruses such as Middle East respiratory syndrome coronavirus or a future newly discovered coronavirus. LeTRS was tested on published data sets and novel clinical samples from patients and longitudinal samples from animal models with coronavirus disease 2019. LeTRS identified known leader–TRS junctions and identified putative novel sgmRNAs that were common across different mammalian species. This may be indicative of an evolutionary mechanism where plasticity in transcription generates novel open reading frames, which can then subject to selection pressure. The data indicated multiphasic abundance of sgmRNAs in two different animal models. This recapitulates the relative sgmRNA abundance observed in cells at early points in infection but not at late points. This pattern is reflected in some human nasopharyngeal samples and therefore has implications for transmission models and nucleic acid–based diagnostics. LeTRS provides a quantitative measure of sgmRNA abundance from sequencing data. This can be used to assess the biology of SARS-CoV-2 (or other coronaviruses) in clinical and nonclinical samples, especially to evaluate different variants and medical countermeasures that may influence viral RNA synthesis.
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