Capturing sequence diversity in metagenomes with comprehensive and scalable probe design
Hayden Metsky
(1, 2)
,
Katherine Siddle
(1, 3)
,
Adrianne Gladden-Young
(1)
,
James Qu
(1)
,
David Yang
(1, 3)
,
Patrick Brehio
(1)
,
Andrew Goldfarb
(3)
,
Anne Piantadosi
(1, 4)
,
Shirlee Wohl
(1, 3)
,
Amber Carter
(1)
,
Aaron Lin
(1, 3)
,
Kayla Barnes
(1, 3, 5)
,
Damien Tully
(6)
,
Bjӧrn Corleis
(6)
,
Scott Hennigan
(7)
,
Giselle Barbosa-Lima
(8)
,
Yasmine Vieira
(8)
,
Lauren Paul
(9)
,
Amanda Tan
(9)
,
Kimberly Garcia
(10)
,
Leda Parham
(10)
,
Ikponmwosa Odia
(11)
,
Philomena Eromon
(12)
,
Onikepe Folarin
(12)
,
Augustine Goba
(13)
,
Etienne Simon-Loriere
(14)
,
Lisa Hensley
(15)
,
Angel Balmaseda
(16)
,
Eva Harris
(17)
,
Douglas Kwon
(4, 6)
,
Todd Allen
(6)
,
Jonathan Runstadler
(18)
,
Sandra Smole
(7)
,
Fernando Bozza
(8)
,
Thiago Souza
(8)
,
Sharon Isern
(9)
,
Scott Michael
(9)
,
Ivette Lorenzana
(10)
,
Lee Gehrke
(2, 19)
,
Irene Bosch
(2)
,
Gregory Ebel
(20)
,
Donald Grant
(13, 21)
,
Christian Happi
(5, 11, 12)
,
Daniel Park
(1)
,
Andreas Gnirke
(1)
,
Pardis Sabeti
(1, 3, 5, 22)
,
Christian Matranga
(1)
1
Broad Institute [Cambridge]
2 MIT - Massachusetts Institute of Technology
3 Harvard University
4 Massachusetts General Hospital [Boston]
5 Harvard T.H. Chan School of Public Health
6 Ragon Institute of MGH, MIT and Harvard
7 Massachusetts Department of Public Health [Boston, MA]
8 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
9 Florida Gulf Coast University
10 UNAH - Universidad Nacional Autónoma de Honduras
11 ISTH - Irrua Specialist Teaching Hospital [Irrua, Nigeria]
12 Redeemer's University [Lagos, Nigeria]
13 Kenema Government Hospital
14 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
15 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
16 MINSA - Ministry of Health [Nicaragua]
17 UC Berkeley - University of California [Berkeley]
18 Tufts University [Medford]
19 HMS - Harvard Medical School [Boston]
20 CSU - Colorado State University [Fort Collins]
21 USL - University of Sierra Leone
22 HHMI - Howard Hughes Medical Institute [Chevy Chase]
2 MIT - Massachusetts Institute of Technology
3 Harvard University
4 Massachusetts General Hospital [Boston]
5 Harvard T.H. Chan School of Public Health
6 Ragon Institute of MGH, MIT and Harvard
7 Massachusetts Department of Public Health [Boston, MA]
8 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
9 Florida Gulf Coast University
10 UNAH - Universidad Nacional Autónoma de Honduras
11 ISTH - Irrua Specialist Teaching Hospital [Irrua, Nigeria]
12 Redeemer's University [Lagos, Nigeria]
13 Kenema Government Hospital
14 Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses
15 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
16 MINSA - Ministry of Health [Nicaragua]
17 UC Berkeley - University of California [Berkeley]
18 Tufts University [Medford]
19 HMS - Harvard Medical School [Boston]
20 CSU - Colorado State University [Fort Collins]
21 USL - University of Sierra Leone
22 HHMI - Howard Hughes Medical Institute [Chevy Chase]
Hayden Metsky
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- PersonId : 1409635
- ORCID : 0000-0002-8871-2349
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David Yang
- Fonction : Auteur
- PersonId : 1409636
- ORCID : 0000-0002-9972-3035
Aaron Lin
- Fonction : Auteur
- PersonId : 1409637
- ORCID : 0000-0001-7400-4125
Lauren Paul
- Fonction : Auteur
- PersonId : 1409638
- ORCID : 0000-0001-5503-7570
Etienne Simon-Loriere
- Fonction : Auteur
- PersonId : 734968
- IdHAL : etiennesimon-loriere
- ORCID : 0000-0001-8420-7743
- IdRef : 136869076
Donald Grant
- Fonction : Auteur
- PersonId : 1254100
- ORCID : 0000-0002-4329-0795
Résumé
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.