Capturing sequence diversity in metagenomes with comprehensive and scalable probe design
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Metsky, Hayden C.
Siddle, Katherine J.
Gladden-Young, Adrianne
Qu, James
Yang, David K.
Brehio, Patrick
Piantadosi, Anne
Carter, Amber
Lin, Aaron E.
Barnes, Kayla G.
Tully, Damien C.
Corleis, Bjӧrn
Hennigan, Scott
Barbosa-Lima, Giselle
Vieira, Yasmine R.
Paul, Lauren M.
Tan, Amanda L.
Garcia, Kimberly F.
Parham, Leda A.
Odia, Ikponmwosa
Eromon, Philomena
Folarin, Onikepe A.
Goba, Augustine
Simon-Lorière, Etienne
Hensley, Lisa
Balmaseda, Angel
Harris, Eva
Kwon, Douglas S.
Allen, Todd M.
Runstadler, Jonathan A.
Smole, Sandra
Bozza, Fernando A.
Souza, Thiago M. L.
Isern, Sharon
Michael, Scott F.
Lorenzana, Ivette
Gehrke, Lee
Bosch, Irene
Ebel, Gregory
Grant, Donald S.
Happi, Christian T.
Park, Daniel J.
Gnirke, Andreas
Matranga, Christian B.
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https://doi.org/10.1038/s41587-018-0006-xMetadata
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Metsky, H.C., Siddle, K.J., Gladden-Young, A. et al. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design. Nat Biotechnol 37, 160–168 (2019). https://doi.org/10.1038/s41587-018-0006-xAbstract
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 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.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42658803
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