• 宏基因组在检测和鉴定含量低的病毒组时,仍需靶向富集测序以提高灵敏度;
  • 本文提出的CATCH算法可设计具有指定数量寡核苷酸的最佳探针集,实现已知序列多样性的覆盖和扩展,捕获宏基因组样本中病毒基因组;
  • 设计、合成和验证多个探针集,一个针对356种人类病毒全基因组的探针集捕获的病毒含量增加了18倍,可实现全基因组组装,并保留样本多样性;
  • 探针组应用捕获重建拉沙热病毒基因组,并改进人类和蚊子样本中未鉴定病毒感染的检测。

Capturing sequence diversity in metagenomes with comprehensive and scalable probe design



2019-02-04, Article

Abstract & Authors:展开

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.

First Authors:
Hayden C Metsky,Katherine J Siddle

Correspondence Authors:
Hayden C Metsky,Katherine J Siddle

All Authors:
Hayden C Metsky,Katherine J Siddle,Adrianne Gladden-Young,James Qu,David K Yang,Patrick Brehio,Andrew Goldfarb,Anne Piantadosi,Shirlee Wohl,Amber Carter,Aaron E Lin,Kayla G Barnes,Damien C Tully,Bjӧrn Corleis,Scott Hennigan,Giselle Barbosa-Lima,Yasmine R Vieira,Lauren M Paul,Amanda L Tan,Kimberly F Garcia,Leda A Parham,Ikponmwosa Odia,Philomena Eromon,Onikepe A Folarin,Augustine Goba,Etienne Simon-Lorière,Lisa Hensley,Angel Balmaseda,Eva Harris,Douglas S Kwon,Todd M Allen,Jonathan A Runstadler,Sandra Smole,Fernando A Bozza,Thiago M L Souza,Sharon Isern,Scott F Michael,Ivette Lorenzana,Lee Gehrke,Irene Bosch,Gregory Ebel,Donald S Grant,Christian T Happi,Daniel J Park,Andreas Gnirke,Pardis C Sabeti,Christian B Matranga