Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
mSphere. 2020 May 6;5(3):e00160-20. doi: 10.1128/mSphere.00160-20.
In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the "virome" keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265-269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270-273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences. Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.
在许多情况下，通过确定感兴趣的序列存在的环境小生境，可以增强对核酸序列生物学意义的跟踪。现在有许多宏基因组数据集，对来自不同生物小生境的样本进行了深度测序。虽然可以使用基于网络的工具轻松查询任何单个宏基因组数据集，但对所有这些数据集进行元搜索则不太容易。在本简讯中，我们展示了一种这样的元宏基因组方法，检查了在可通过“病毒组”关键字访问的 NCBI Sequence Read Archive 中所有高通量测序数据集中与严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）的紧密匹配。除了在描述 SARS-CoV-2 序列时观察到的与蝙蝠冠状病毒的同源性（F. Wu, S. Zhao, B. Yu, Y. M. Chen, 等人，Nature 579:265-269, 2020, https://doi.org/10.1038/s41586-020-2008-3；P. Zhou, X. L. Yang, X. G. Wang, B. Hu, 等人，Nature 579:270-273, 2020, https://doi.org/10.1038/s41586-020-2012-7）外，我们还注意到刘等人从死亡穿山甲肺部生成的宏病毒组数据集中的许多序列读数具有很强的同源性（P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979）。尽管对这些读数的分析表明在穿山甲肺部存在类似的病毒序列，但这种相似性不足以确认或排除穿山甲作为 SARS-CoV-2 最近出现的中间宿主的作用。除了对 SARS-CoV-2 出现的影响外，本研究还说明了元宏基因组搜索工具在有效和快速描述潜在重要核酸序列方面的实用性和局限性。元宏基因组搜索允许高速、低成本地识别感兴趣序列的潜在重要生物小生境。
