Fig. 3.

Sequential and simultaneous mutation pairs are enriched in functional categories. We determine the identity of the top 100 pairs of significant hits for (A) sequential mutation pairs and (C) simultaneous mutation pairs. We categorize mutation pairs as those where a known resistance mutation occurs first, known resistance mutation occurs second, both mutations are known resistance mutations, one mutation is in a known antigen protein, both mutations are in a known antigen protein, or other category (not any of the above). For simultaneous mutations, we compute the categories for the top 100 hits found within 100 bp on the genome and for the top 100 hits found outside 100 bp. The genomic distance in megabases of all pairs of significant dependent mutations for (B) sequential mutations and (D) simultaneous mutations are shown.