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

Consider a large set of input sequences that encompass a diverse set of taxa (e.g., hundreds of viral species). We could run CATCH, as described above, on a single choice of parameters θ d such that the number of probes in s(d, θ d ) is feasible for synthesis. However, this can lead to a poor representation of taxa in the diverse probe set; it can become dominated by probes covering taxa that have more genetic diversity (e.g., HIV-1). Furthermore, it can force probes to be designed with relaxed assumptions about hybridization across all taxa. To alleviate these issues, we allow different choices of parameters governing hybridization for different subsets of input sequences, so that some can have probes designed with more relaxed assumptions than others.