Figure 1

Model for classifying interactions as additive or non-additive. The interaction of effects between gene deletion and a second perturbation is quantified by comparison between the reference strain and each deletion strain over a range of perturbation-induced effects. Six hypothetical deletion strains are depicted to illustrate the contrast between additive and non-additive interaction. (a) The 'phenotypic slope' of the reference strain (filled circles) defines the effect of perturbation on the reference strain. The effect of gene deletion is determined in the absence of perturbation, and typically has either no effect (strains 1, 3, and 5) (filled square) or a negative effect (strains 2, 4, and 6) (open square) on growth. (b) Additive gene interactions are defined by the phenotypic slope of the deletion strain being parallel to that of the reference strain, across a range of perturbations (strains 1 and 2). (c,d) Non-additive gene interactions can be either synergistic (c), giving a phenotypic slope of greater absolute value (strains 3 and 4), or antagonistic (d), giving a phenotypic slope of lesser absolute value (strains 5 and 6). Two types of antagonistic interactions are depicted in (d). Deletion strain 5 is absolutely antagonistic to the perturbation (for example, drug resistance due to loss of a transporter required for drug uptake), whereas deletion strain 6 is antagonistic only when the inhibitory effect of the deletion alone is greater than that of the perturbation alone (for example, drug resistance due to deletion of the gene encoding the protein target of drug inhibition).