RT Journal Article
SR Electronic
T1 Capturing diverse microbial sequence with comprehensive and scalable probe design
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 279570
DO 10.1101/279570
A1 Katherine J. Siddle
A1 Hayden C. Metsky
A1 Adrianne Gladden-Young
A1 James Qu
A1 David K. Yang
A1 Patrick Brehio
A1 Andrew Goldfarb
A1 Anne Piantadosi
A1 Shirlee Wohl
A1 Aaron E. Lin
A1 Kayla G. Barnes
A1 Damien C. Tully
A1 Scott Hennigan
A1 Giselle Barbosa-Lima
A1 Yasmine R. Vieira
A1 Lauren M. Paul
A1 Amanda L. Tan
A1 Kimberly F. Garcia
A1 Leda A. Parham
A1 Ikponmwonsa Odia
A1 Philomena Eromon
A1 Onikepe A. Folarin
A1 Augustine Goba
A1 Viral Hemorrhagic Fever Consortium
A1 Etienne Simon-Lorière
A1 Lisa Hensley
A1 Angel Balmaseda
A1 Eva Harris
A1 Todd M. Allen
A1 Jonathan A. Runstadler
A1 Sandra Smole
A1 Fernando A. Bozza
A1 Thiago M. L. Souza
A1 Sharon Isern
A1 Scott F. Michael
A1 Ivette Lorenzana
A1 Lee Gehrke
A1 Irene Bosch
A1 Gregory Ebel
A1 Christian Happi
A1 Donald Grant
A1 Daniel J. Park
A1 Andreas Gnirke
A1 Pardis C. Sabeti
A1 Christian B. Matranga
YR 2018
UL http://biorxiv.org/content/early/2018/03/12/279570.abstract
AB Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa, and implemented it in a publicly available software package. CATCH designs compact probe sets that achieve full coverage of known microbial sequence diversity and that scale well with this diversity. Using CATCH, we designed and synthesized multiple probe sets, including one to capture whole genomes of the 356 viral species known to infect humans, and conducted a rigorous evaluation of their performance. Capture with these probe sets enriched unique viral content on average 18 × in sequencing libraries from patient and environmental samples and allowed us to assemble viral genomes that we could not otherwise recover. We show that capture accurately reflects co-infections and within-host nucleotide variation, enriches sequence with substantial divergence from the probe sets, and improves detection of viral infections in samples with unknown microbial content. Our work provides a new approach to probe design and evaluation, and demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.