Alignment of the protein interaction networks of herpesviruses VZV and KSHV. a) The alignment maps the nodes from the highlighted sub-networks of the PINs. Nodes are colour coded according to sequence similarity, measured by the sequence alignment score θ [see Additional file 1]. Green nodes have high sequence similarity with θ > 0, red nodes have no sequence similarity detected, red/green nodes have low similarity with θ ≤ 0. The ORFs that do not belong to the network alignment are shown in pale colours. Protein interactions are represented by links between nodes, interactions between ORFs in the alignment are shown in blue. Supplementary animation [Additional file 2] puts the aligned network further into the context of the PINs. b) The optimal alignment is shown with nodes representing aligned pairs of ORFs. Green links indicate interactions which have been detected in both KSHV and VZV. Interactions which have only been detected in KSHV or VZV are shown in magenta or red, respectively. The cluster of matching interactions linking nodes KSHV ORF23/VZV ORF39, 29b/42, 28/65, and 67.5/25 is highlighted. c) From the alignment to functional annotation: We show the alignment of the VZV ORF65 with KSHV ORF28 (central nodes) and the context in the protein interaction graphs. The aligned partners are connected with dashed lines, the green lines connect ORFs with significant sequence similarity and the red lines connect ORFs that are aligned solely due to similarity of their interactions. An ORF belongs either among structural ORFs (green squares) or information-processing ORFs (red squares), or its function is unknown (white squares). According to the alignment of KSHV ORF28 to VZV ORF65 the KSHV ORF28 is predicted to belong among structural genes. The fact that all but one of its conserved interacting partners have the same functional annotation further supports this prediction (guilt by conserved association).