Improved prediction of missing protein interactome links via anomaly detection.

Interactomes such as Protein interaction networks have many undiscovered links between entities. Experimental verification of every link in these networks is prohibitively expensive, and therefore computational methods to direct the search for possible links are of great value. The problem of finding undiscovered links in a network is also referred to as the link prediction problem. A popular approach for link prediction has been to formulate it as a binary classification problem in which class labels indicate the existence or absence of a link (we refer to these as positive links or negative links respectively) between a pair of nodes in the network. Researchers have successfully applied such supervised classification techniques to determine the presence of links in protein interaction networks. However, it is quite common for protein-protein interaction (PPI) networks to have a large proportion of undiscovered links. Thus, a link prediction approach could incorrectly treat undiscovered positive links as negative links, thereby introducing a bias in the learning. In this paper, we propose to denoise the class of negative links in the training data via a Gaussian process anomaly detector. We show that this significantly reduces the noise due to mislabelled negative links and improves the resulting link prediction accuracy. We evaluate the approach by introducing synthetic noise into the PPI networks and measuring how accurately we can reconstruct the original PPI networks using classifiers trained on both noisy and denoised data. Experiments were performed with five different PPI network datasets and the results indicate a significant reduction in bias due to label noise, and more importantly, a significant improvement in the accuracy of detecting missing links via classification.