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

We next applied our V ALL probe set to pools of human plasma and mosquito samples with uncharacterized infections. We tested 5 pools of human plasma from a total of 25 individuals with suspected LASV or EBOV infections from Sierra Leone, as well as 5 pools of human plasma from a total of 25 individuals with acute fevers of unknown cause from Nigeria and 5 pools of Culex tarsalis and Culex pipiens mosquitoes from the United States (see Methods for details). Using V ALL we detected 8 viral species, each present in one or more pools: 2 species in the pools from Sierra Leone, 2 species in the pools from Nigeria, and 4 species in the 10 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It mosquito pools (Fig. 4b, Supplementary Fig. 6c ). We found consistent results with V WAFR for the species that were included in its design ( Supplementary Fig. 6d , Supplementary Table 4 ). To confirm the presence of these viruses we assembled their genomes and evaluated read depth ( Supplementary Fig. 11 , Supplementary Table 8) . We also sequenced pre-capture samples and saw significant enrichment by capture (Fig. 4c , Supplementary Fig. 6c , d).