Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice

Tchitchek, Nicolas; Eisfeld, Amie J; Tisoncik-Go, Jennifer; Josset, Laurence; Gralinski, Lisa E; Bécavin, Christophe; Tilton, Susan C; Webb-Robertson, Bobbie-Jo; Ferris, Martin T; Totura, Allison L; Li, Chengjun; Neumann, Gabriele; Metz, Thomas O; Smith, Richard D; Waters, Katrina M; Baric, Ralph; Kawaoka, Yoshihiro; Katze, Michael G

The Magnitude Coefficient (MC) quantifies the magnitude effect as the transcriptomic distance from one biological condition to the matched mock-infected condition. The Velocity Coefficient (VC) quantifies the velocity effect as the speed of the transcriptomic host response to move from one time point to the next one. Both the MC and VC were calculated based on the centroids (arithmetic means) of the biological conditions and the transcriptomic distances (Euclidian distances) are calculated based on the lists of transcripts associated with the kinetics of the host response to VN1203 wild-type. Namely the MC and VC of a biological condition bc t being the mean vector of gene expression levels amongst the biological replicates at the time point t are defined as: where: mock represents the mean vector of gene expression levels amongst the matched mock-infected samples, Δt is the amount of time between t and t+1 in days, and n is the length of the mean vectors of gene expression.