Accurate viral genome reconstruction and host assignment with proximity-ligation sequencing
Accurate viral genome reconstruction and host assignment with proximity-ligation sequencing
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通过邻近连接测序进行准确的病毒基因组重建和宿主分配
DOI：
10.1101/2021.06.14.448389
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Uritskiy, G.
中科院分区：
文献类型：
--
作者：
Uritskiy, G.
病毒在微生物群落的生态中起着至关重要的作用，但它们在其原生环境中的研究仍然相对不足。尽管在高通量全基因组测序（WGS）、序列组装和病毒注释方面取得了许多进展，但直接从宏基因组测序中重建全长病毒基因组仅适用于最丰富的噬菌体，并且需要长读测序技术。此外，仅通过常规的宏基因组测序预测它们的细胞宿主仍然很困难。为了解决该领域的这些空白，并加速直接在其原生微生物组中研究病毒，我们开发了一个端到端的生物信息学平台，使用邻近连接测序（即Hi-C）从宏基因组数据中进行病毒基因组重建和宿主归因。我们通过恢复和表征各种宏基因组的元病毒组来展示该平台的功能，包括粪便微生物组，该微生物组也已被精确的长读数测序，从而允许评估和对新方法进行基准测试。该平台可以准确地提取大量近乎完整的病毒基因组，甚至可以从高度碎片化的短读片段中提取，并且可以以最小的假阳性可靠地预测它们的细胞宿主。据我们所知，这是第一个执行这些任务的软件。与同等深度的长读测序相比，近端连接测序的成本要低得多，因此在微生物组研究中引入近端连接测序有望大大加快该领域的未来发展。
Viruses play crucial roles in the ecology of microbial communities, yet they remain relatively understudied in their native environments. Despite many advancements in high-throughput whole-genome sequencing (WGS), sequence assembly, and annotation of viruses, the reconstruction of full-length viral genomes directly from metagenomic sequencing is possible only for the most abundant phages and requires long-read sequencing technologies. Additionally, the prediction of their cellular hosts remains difficult from conventional metagenomic sequencing alone. To address these gaps in the field and to accelerate the study of viruses directly in their native microbiomes, we developed an end-to-end bioinformatics platform for viral genome reconstruction and host attribution from metagenomic data using proximity-ligation sequencing (i.e., Hi-C). We demonstrate the capabilities of the platform by recovering and characterizing the metavirome of a variety of metagenomes, including a fecal microbiome that has also been sequenced with accurate long reads, allowing for the assessment and benchmarking of the new methods. The platform can accurately extract numerous near-complete viral genomes even from highly fragmented short-read assemblies and can reliably predict their cellular hosts with minimal false positives. To our knowledge, this is the first software for performing these tasks. Being significantly cheaper than long-read sequencing of comparable depth, the incorporation of proximity-ligation sequencing in microbiome research shows promise to greatly accelerate future advancements in the field.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
--
影响因子：
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DOI：
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发表时间：
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期刊：
影响因子：
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