Abstract
BackgroundThe 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.ResultsHere, 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.ConclusionThese 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.
Highlights
The use of computational methods for predicting protein interaction networks will continue to grow with the number of fully sequenced genomes available
Phylogenetic profiling methods work by i) creating a Phylogenetic profile vector where Pij = 1 indicates a homolog exists between protein i in the target genome and a protein in a reference genome j, ii) calculating similarity measurements on the profile vectors for each pair of genes in the target genome, and iii) defining protein interactions in the target genome based on proteins sharing a profile similarity value greater than a threshold value
Using E. coli K12 as the target genome, we have evaluated how changing different aspects of this process, including the use of a new metric for defining similarity, affect predicted protein interaction networks
Summary
The use of computational methods for predicting protein interaction networks will continue to grow with the number of fully sequenced genomes available. An alternative method for predicting protein function is the Phylogenetic profile method, known as the CoConservation method, which rests on the premise that functionally related proteins are gained or lost together over the course of evolution [4]. This method predicts functional interactions between pairs of proteins in a target organism by determining whether both proteins are consistently present or absent across a set of reference genomes. Sequence similarity is used only (page number not for citation purposes)
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