Fus3 is required for deletions of GIM4 and BIM1 to increase cell‐to‐cell variability Fus3 is required for deletions of GIM4 and BIM1 to increase cell‐to‐cell variability Deletions of FUS3 and KSS1 have distinct effects on the increased cell‐to‐cell variability caused by deletions of GIM4 and BIM1. We induced the PRS in the indicated strains by addition of 20 nM pheromone to the medium and measured reporter activity after 3 h. Y‐axis in each panel shows η2(P) as a function of P. Deletion strains derive from the reference WT GPY4000. Δbim1 and Δgim4 strains show increased η2(P) relative to WT (P‐values are both less than 10−5), while Δfus3 ∆bim1 and Δfus3 ∆gim4 strains show η2(P) not distinguishable from WT (P‐values are 0.341 and 0.095, respectively). However, ∆bim1 Δkss1 and ∆gim4 Δkss1 cells show higher η2(P) relative to WT (P‐values are both less than 10−5). The double mutant Δbim1 Δkss1 had significantly higher η2(P) than either Δkss1 or Δbim1 alone (P‐values are both 10−5 or less), while the double mutant Δgim4 Δkss1 had essentially the same η2(P) as either Δkss1 or Δgim4 alone (P‐values are 0.341 and 0.106, respectively). This shows that Fus3 protein is required for increased η2(P). (All strains have three replicates except for one of the double deletions, Δfus3 ∆bim1, which has two replicates.) To compare the piecewise‐linear curves implied by the data from each pair of strains, we use an Area Between the Curves (ABC) metric, with each area estimated by trapezoidal integration. We then obtain the P‐values by resampling over the replicates under the null hypothesis that the two strains are in fact the same; the P‐value is the number of times that the resampled ABC was at least as far from the median as the realized ABC.P vs. dose for the datasets of panel (A). Source data are available online for this figure. C Gustavo Pesce et al. Mol Syst Biol 2018;14:e7390 © as stated in the article, figure or figure legend