  Sequence alignment forms the basis of many methods for functional annotation
by phylogenetic comparison, but becomes unreliable in the `twilight' regions of
high sequence divergence and short gene length. Here we perform a cross-species
comparison of two herpesviruses, VZV and KSHV, with a hybrid method called
graph alignment. The method is based jointly on the similarity of protein
interaction networks and on sequence similarity. In our alignment, we find open
reading frames for which interaction similarity concurs with a low level of
sequence similarity, thus confirming the evolutionary relationship. In
addition, we find high levels of interaction similarity between open reading
frames without any detectable sequence similarity. The functional predictions
derived from this alignment are consistent with genomic position and gene
expression data.
