Four-dimensional visualisation and analysis of protein-protein interaction networks.

Protein-protein interaction networks are typically built with interactions collated from many experiments. These networks are thus composite and show all interactions that are currently known to occur in a cell. However, these representations are static and ignore the constant changes in protein-protein interactions. Here we present software for the generation and analysis of dynamic, four-dimensional (4-D) protein interaction networks. In this, time-course-derived abundance data are mapped onto three-dimensional networks to generate network movies. These networks can be navigated, manipulated and queried in real time. Two types of dynamic networks can be generated: a 4-D network that maps expression data onto protein nodes and one that employs 'real-time rendering' by which protein nodes and their interactions appear and disappear in association with temporal changes in expression data. We illustrate the utility of this software by the analysis of singlish interface date hub interactions during the yeast cell cycle. In this, we show that proteins MLC1 and YPT52 show strict temporal control of when their interaction partners are expressed. Since these proteins have one and two interaction interfaces, respectively, it suggests that temporal control of gene expression may be used to limit competition at the interaction interfaces of some hub proteins. The software and movies of the 4-D networks are available at http://www.systemsbiology.org.au/downloads_geomi.html.