Capturing diverse microbial sequence with comprehensive and scalable probe design

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; Björn Corleis; Scott Hennigan; Giselle Barbosa-Lima; Yasmine R. Vieira; Lauren M. Paul; Amanda L. Tan; Kimberly F. Garcia; Leda A. Parham; Ikponmwonsa Odia; Philomena Eromon; Onikepe A. Folarin; Augustine Goba; Etienne Simon-Lorière; Lisa Hensley; Angel Balmaseda; Eva Harris; Douglas 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 Grant; Christian Happi; Daniel J. Park; Andreas Gnirke; Pardis C. Sabeti; Christian B. Matranga

Previous studies have used targeted amplification 11, 12 or enrichment via capture of viral nucleic acid using oligonucleotide probes [13] [14] [15] to improve the sensitivity of sequencing for specific viruses. However, achieving comprehensive sequencing of viruses -similar to the use of microarrays for differential detection 16-22 -is challenging due to the enormous diversity of viral genomes. One recent study used a probe set to target a large panel of viral species simultaneously, but did not attempt to cover strain diversity 23 . Other studies have designed probe sets to more comprehensively target viral diversity and tested their performance 24, 25 . These overcome the primary limitation of single virus enrichment methods, i.e., having to know a priori the taxon of interest. However, existing probe sets that target viral diversity have been designed with ad hoc approaches and they are not publicly available.