Detecting Rewiring Events in Protein-Protein Interaction Networks Based on Transcriptomic Data

Proteins rarely carry out their cellular functions in isolation. Instead, eukaryotic proteins engage in about six interactions with other proteins on average. The aggregated protein interactome of an organism forms a "hairy ball"-type protein-protein interaction (PPI) network. Yet, in a typical human cell, only about half of all proteins are expressed at a particular time. Hence, it has become common practice to prune the full PPI network to the subset of expressed proteins. If RNAseq data is available, one can further resolve the specific protein isoforms present in a cell or tissue. Here, we review various approaches, software tools and webservices that enable users to construct context-specific or tissue-specific PPI networks and how these are rewired between two cellular conditions. We illustrate their different functionalities on the example of the interactions involving the human TNR6 protein. In an outlook, we describe how PPI networks may be integrated with epigenetic data or with data on the activity of splicing factors.