Pairs of genes that function together in a pathway or cellular system can 
sometimes be found fused together in another organism as a Rosetta Stone 
protein--a fusion protein whose separate domains are homologous to the two 
functionally-related proteins. The finding of such a Rosetta Stone protein 
allows the prediction of a functional linkage between the component proteins. 
The significance of these deduced functional linkages, however, varies depending 
on the prevalence of each of the two domains. Here, we develop a statistical 
measure for the significance of predicted functional linkages, and test this 
measure for proteins of E. coli on a functional benchmark based on the KEGG 
database. By applying this statistical measure, proteins can be linked with over 
70% accuracy. Using the Rosetta Stone method and this scoring scheme, we find 
all significant functional linkages for proteins of E. coli, P. horikshii and S. 
cerevisiae, and measure the extent of the resulting protein networks.