Handling noise in protein interaction networks

Abstract

Protein-protein interactions (PPI) can be conveniently represented as networks, allowing the use of graph theory in their study. Network topology studies may reveal patterns associated to specific organisms. Here we propose a new methodology to denoise PPI networks and predict missing links solely based on the network topology, the Organization Measurement (OM) method. The OM methodology was applied in the denoising of the PPI networks of two Saccharomyces Cerevisiae datasets (Yeast and CS2007) and one Homo Sapiens dataset (Human). To evaluate the denoising capabilities of OM methodology, two strategies were applied. The first compared its application in random networks and in the reference set networks, while the second perturbed the networks with the gradual random addition and removal of edges. The application of OM methodology to the Yeast and Human reference sets achieved an AUC of 0.95 and 0.87, in Yeast and Human networks, respectively. The random removal of 80% of the Yeast and Human reference sets interactions resulted in an AUC of 0.71 and 0.62, whereas the random addition of 80% interactions resulted in an AUC of 0.75 and 0.72, respectively. Applying the OM methodology to the CS2007 dataset yields an AUC of 0.99. We also perturbed the network of the CS2007 dataset by randomly inserting and removing edges in the same proportions previously described. The false positives identified and removed from the network varied from 97%, when inserting 20% more edges, to 89% when 80% more edges were inserted. The true positives identified and inserted in the network varied from 95% when removing 20% of the edges, to 40% after the random deletion 80% edges. The OM methodology is sensitive to the topological structure of the biological networks. The obtained results suggest that the present approach can efficiently be used to denoise PPI networks.