Apart from general topological features, herpesviral interactomes were also compared on the level of individual interactions. For this purpose, we used the orthology assignments based on sequence similarity and gene order (Table S5 ) [31] . Species within the same subfamily are generally characterized by higher sequence similarity between orthologous proteins. They also share more orthologous proteins with each other than species from different subfamilies ( Figure 2A ). In previous inter-species comparisons [32] , very few interactions were found to be shared between different species (yeast, worm, fly). Unlike the previous comparative studies, the five different interactomes analysed in this study were obtained using exactly the same experimental protocols. Nevertheless, we still observed little overlap between the networks of the five herpesviruses. Of 488 (409 non-redundant, i.e. conserved interactions are only counted once) interactions between proteins conserved in more than one species, 140 (61 non-redundant) (28.7% or 14.9% non-redundant, respectively) interactions were conserved between at least two species. For any two herpesvirus species, we compared the number of interactions between proteins conserved in both species against the number of interactions found in both species ( Figure 2B ). Although the pair