Protein-Protein Interactions and Disease

Abstract

1. Introduction Protein-protein interactions (PPI), in which, two or more proteins associate with each other by various means, are key to understanding all biological processes that occur within as well as between cells. In effect, biological processes are essentially interactions between multiple proteins (Zhang et al., 2011) with PPI networks controlling the flow of information both within and between biological processes. Disruptions in PPI networks have been shown to result in diseases. This includes monogenic diseases such as hemophilia where a particular biochemical pathway is disrupted, as well as more complex diseases such as cancer, which involve several signaling pathways (Sam et al., 2007). Conversely, disruption of a set of PPI can lead to a particular disease or, in the case where the set is shared among several networks, to several diseases. While there is a wealth of protein-disease associations in the published literature that have been incorporated in PPI repositories, the challenge is to link such PPI to human disease (Ideker & Sharan, 2008). In this chapter we discuss several examples of diseases that are caused by disruptions of PPI networks. Our goal is to illustrate through examples how the role of PPI in disease can be studied using a variety of computational tools and data sources. While we discuss tools and data sources that are of general interest, we also discuss methods for studying specific diseases and methods aimed at large scale analysis of PPI data to identify classes of diseases. In each case we provide specific examples from the literature and a brief discussion of the tools used.