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

(c) Number of probes designed by CATCH for each dataset (of 296 datasets in total) among all 349,998 probes in the V ALL probe set. Species incorporated in our sample testing are labeled. (d) Values of the two parameters selected by CATCH for each dataset in the design of V ALL : number of mismatches to tolerate in hybridization and length of the target fragment (in nt) on each side of the hybridized region assumed to be captured along with the hybridized region (cover extension). The label and size of each bubble indicate the number of datasets that were assigned a particular combination of values. Species included in our sample testing are labeled in black, and outlier species not included in our testing are in gray. In general, more diverse viruses (e.g., HCV and HIV-1) are assigned more relaxed parameter values (here, high values) than less diverse viruses, but still require a relatively large number of probes in the design to cover known diversity (see (c)). Panels similar to (c) and (d) for the design of V WAFR are in Supplementary Fig. 3 .