Prevalence of epistasis in the evolution of influenza A surface proteins.

In H3, we identified 333 site pairs with a nominally significant epistasis statistic; we identified 225 such pairs in H1, 205 such pairs in N1, and 188 such pairs in N2 (see Table 1 , and Table S1 ).

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We applied this method to identify putative epistatic pairs in the influenza surface proteins hemagglutinin and neuraminidase, and we found a highly significant number of interacting pairs.

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