Figure 2

Overview of phenotypic array and growth index (GI). Growth is quantified by image analysis of cellular arrays and plotted against time to calculate area under the growth curve (AUGC), which is used to calculate the growth index (GI) a predictor of non-additive gene interaction. (a-f) Raw data from growth of a single deletion strain source plate (plate 4, see Additional data file 7) at three different times, 26 h (a,d), 46 h (b,e), and 94 h (c,f), and under two different conditions, synthetic complete medium without HU (a-c) and with 150 mM HU (d-f). Only three strains (E2, E10 and G2) were selected for further testing from this plate, having GI < -5.8. (g,h) Growth curves (red) for all 94 strains are plotted, along with the mean growth (blue dashed line) from 196 replicates of the reference strain, in (g) the absence or (h) the presence of 150 mM HU. (i) The GI equation is a z-statistic, where the difference between normalized growth of the deletion and mean of reference strains is the signal for non-additive interaction, and the standard deviation of the reference strain growth is the noise. [], concentration of HU (mM); ds, deletion strain; ref, reference strain; n, number of replicates; SD, standard deviation. (j) The distribution of GI scores for all strains (except 64 strains with unperturbed AUGC < 600, see Additional data files 2, 7) from the 50 mM (red triangles) and 150 mM (blue crosses) HU screens (n = 4,788, bin size = 0.5), along with the distribution of reference strain GI values (dashed lines) (n = 192, bin size = 1; range: -2.41 < GI < 2.15). REF, reference strain. (k) Plot of intrinsic growth (AUGC when unexposed to drugs) vs phenotypic interaction with HU (GI) is shown for all deletion strains. Dashed lines indicate the GI cutoffs used to select synergistic (GI < -5.8) or antagonistic (GI > 5.8) interactions for further testing.