Investigation of factors affecting prediction of protein-protein interaction networks by phylogenetic profiling

The use of computational methods for predicting protein interaction networks will continue to grow with the number of fully sequenced genomes available. The Co-Conservation method, also known as the Phylogenetic profiles method, is a well-established computational tool for predicting functional relationships between proteins.

Here, we examined how various aspects of this method affect the accuracy and topology of protein interaction networks. We have shown that the choice of reference genome influences the number of predictions involving proteins of previously unknown function, the accuracy of predicted interactions, and the topology of predicted interaction networks. We show that while such results are relatively insensitive to the E-value threshold used in defining homologs, predicted interactions are influenced by the similarity metric that is employed. We show that differences in predicted protein interactions are biologically meaningful, where judicious selection of reference genomes, or use of a new scoring scheme that explicitly considers reference genome relatedness, produces known protein interactions as well as predicted protein interactions involving coordinated biological processes that are not accessible using currently available databases.

These studies should prove valuable for future studies seeking to further improve phylogenetic profiling methodologies as well for efforts to efficiently employ such methods to develop new biological insights.