Thu 11 Feb. 2010, 10:30
Title: Rational prediction, analysis and annotation of protein-protein interactions
Speaker: Igor Jurišica, University of Toronto
While high-throughput methods can help to identify large numbers of protein and genetic interactions, and to interrogate gene regulation, signalling, and metabolic networks and pathways, their overlap is usually low. Even when combined with curated and interologous interactions, this only covers about 13% of the estimated human interactome. We need to accelerate and focus these studies, and make optimal choices for the specific methods to be used in order to characterize high priority cancer-related targets. At present, approximately 40% of cancer signature genes do not have protein-protein interaction information. Many of these interactions can be predicted with high confidence using data mining approach - fpClass algorithm. As a first step, we consider UniProt with 74,946 proteins, comprising 36,899 proteins with non-redundant sequences and 23,013 protein fragments. Using fpClass we have predicted ~2.6 billion pairs with diverse probability of interaction among all 74,946 proteins. Second, we use text mining to increase the number of papers supporting curated, high-throughput and predicted interactions. Besides providing more confidence, this information will provide context . potentially identifying multiple methods used to detect a given PPIs, identifying region of the protein used to detect PPI, in what tissue and under what conditions. In turn, this may be useful to plan follow-up validation experiments. Third, we use NAViGaTOR, a powerful graphing application for the 2D and 3D visualization of biological networks. NAViGaTOR includes a rich suite of visual mark-up tools for manual and automated annotation, fast and scalable layout algorithms, and OpenGL hardware acceleration to facilitate scalable visualization of large graphs, combined with graph theory algorithms to analyze topological features in networks. Publication-quality images can be rendered through SVG graphics export, and many community-developed data formats support data import/export (PSI-XML, BioPax, and GML). NAViGaTOR's ability to handle larger datasets is facilitated through optimized layout algorithms, hardware-based graphics acceleration, and a reduced memory footprint relative to other software. The NAViGaTOR user interface includes unique tools to help simplify the "hairball", which is a common challenge in many interaction networks.