Estimating significance for S scores. (a) Schematic illustrating the strategy used to estimate the distribution of S scores arising from noninteracting gene pairs. The distribution of pairs of scores lying close to the 'Noise' axis (that is, pairs with an average score close to zero) were assumed to arise from noninteracting gene pairs. (b) Fit (with residuals shown below) of the distribution of scores lying close to the 'Noise' axis in (a) according to the model that individual S scores for noninteracting gene pairs follow a t-distribution (see Materials and methods for further explanation). (c) Plot of an estimate of the fraction of observations, as a function of averaged S score, that correspond to genuine genetic interactions.