Capturing sequence diversity in metagenomes with comprehensive and scalable probe design
Capturing sequence diversity in metagenomes with comprehensive and scalable probe design
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DOI：
10.1038/s41587-018-0006-x
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发表时间：
2019-02-01
影响因子：
46.9
通讯作者：
Matranga, Christian B.
中科院分区：
文献类型：
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作者：
Metsky, Hayden C.;Siddle, Katherine J.;Matranga, Christian B.
宏基因组测序有可能改变微生物检测和表征，但需要新的工具来提高其灵敏度。在这里，我们提出了CATCH，一种计算方法来增强核酸捕获，以丰富不同的微生物分类群。CATCH设计了最优的探针集，具有指定数量的寡核苷酸，可以实现已知序列多样性的完全覆盖，并且可以很好地扩展。我们专注于应用CATCH捕获复杂宏基因组样本中的病毒基因组。我们设计、合成并验证了多个探针集，包括一个针对已知感染人类的356种病毒的全基因组的探针集。使用这些探针集捕获的独特病毒内容平均丰富18倍，使我们能够组装不富集就无法恢复的基因组，并准确地保留样品内的多样性。我们还使用这些探针集恢复尼日利亚2018年拉沙热暴发的基因组，并改进对人类和蚊子样本中未表征的病毒感染的检测。结果表明，CATCH使宏基因组测序更加敏感和具有成本效益。
Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of, and scale well with, known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets the whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.