Fig. 5: Accurate prediction of drug resistance mutations in SNP-accessible space.
From: Decoding efficacy and resistance space at a drug binding site
a The lower left-hand half of the plot illustrates the mutability of a given codon into any other codon via exchange of one (single nucleotide variant, SNV, white), two (double nucleotide variant, DNV, orange) or three (triple nucleotide variant, TNV, blue) nucleotides. The upper right-hand half of the plot shows those codon edits observed in our DDD247-resistance MOT-library screening profile, with SNVs shown in green, and transitional SNVs also framed. b The radial plots show dose-response data for two DDD247-resistance hotspots observed in the proteasome β5 subunit in our MOT-library profiling screens (Fig. 2d), indicating that resistance is only accessible via SNVs at the Y113 hotspot. TAC113Y can access TGCC, GACD, TTCF, CACH, AACN and TCCS via an SNV, all predicted to yield resistance. TCC132S can access GCCA, TGCC, TTCF, CCCP, ACCT and TACY via SNVs, but none of these are predicted to yield resistance. Transitions, **; transversions, *, black arcs denote synonymous and stop codons. c Sanger sequencing data for five spontaneous and predicted SNVs in the proteasome β5 subunit associated with DDD247-resistance. *, indicates mutated bases.
