Figure 4.

Epistatic pairs of AAs detected in the Koel13HA data set. (A) The epistatic mutations that we detected are plotted on the HA phylogenetic tree. The substitutions in red were experimentally validated to be responsible for cluster change (Koel et al. 2013). The antigenic clusters are named after the first vaccine strain in the cluster, with letters and digits referring to location and year of isolation (HK, Hong Kong; EN, England; VI, Victoria; TX, Texas; BK, Bangkok; SI, Sichuan; BE, Beijing; WU, Wuhan; SY, Sydney; FU, Fujian). (B) The thickness of the links is proportional to $-{\log }_{10}P$-values, the strength of evidence supporting the interaction. (C) The epistatic sites are mapped on a three-dimensional HA protein structure (based on template 3WHE). The numbers show the AA positions experimentally validated (in red) and those detected only in this study (in black). The numbers in purple show the physical distance between epistatic sites (in Å).