Fig. 1

Methodology overview and experimental design. a The proposed workflow for identifying pairwise epistatic interaction is shown. Key methodologies are boxed. b The experimental scheme is shown. Briefly, 293T cells (represented by the red flask) were transfected with the randomly mutagenized M segment (DNA library) and the other seven WT segments to generate the viral mutant library. This viral mutant library was used to infect A549 cells (represented by the orange flask) for 24-hour to generate the post-infection library. The DNA library and the post-infection library were subjected to deep sequencing