Fig. 2. Within- and between-pathway models for genetic interactions. Synthetic lethal interactions (broken lines) can occur both between two components of a single biochemical pathway (A), or between components of two parallel pathways that can functionally compensate for each other (B). Kelley and Ideker found that the combination of within- and between-pathway models could explain about 40% of synthetic lethal or sick interactions in yeast, with between-pathway models predominating. Examples of within-pathway interactions include interactions among components of the spliceosome, and interactions among components of the casein kinase 2 complex. Between-pathway interactions include extensive interactions between components of the Dynactin complex and components of the Prefoldin complex (Kelley and Ideker, 2005). For interactions between partial loss-of-function mutations, however, within-pathway models may predominate. Genes/proteins are shown as nodes, protein interactions as solid edges, and genetic interactions as broken edges.