Protein-protein interaction networks: the puzzling riches

While major progress has been achieved in the experimental techniques used for the detection of protein interactions and in the processing and analysis of the vast amount of data that they generate, we still do not understand why the set of identified interactions remains so highly dependent on the particular detection method. Here we present an overview of the major high-throughput experimental methods used to detect interactions and the datasets produced using these methods over the last 10 years. We discuss the challenges of assessing the quality of these datasets, and examine key factors that likely underlie the persistent poor overlap between the interactions detected by different methods. Lastly, we present a brief overview of the literature-curated protein interaction data stored in public databases, which are often relied upon for independent validation of newly derived interaction networks.