GreedyPlus: An Algorithm for the Alignment of Interface Interaction Networks

The increasing ease and accuracy of protein-protein interaction detection has resulted in the ability to map the interactomes of multiple species. We now have an opportunity to compare species to better understand how interactomes evolve. As DNA and protein sequence alignment algorithms were required for comparative genomics, network alignment algorithms are required for comparative interactomics. A number of network alignment methods have been developed for protein-protein interaction networks, where proteins are represented as vertices linked by edges if they interact. Recently, protein interactions have been mapped at the level of amino acid positions, which can be represented as an interface-interaction network (IIN), where vertices represent binding sites, such as protein domains and short sequence motifs. However, current algorithms are not designed to align these networks and generally fail to do so in practice. We present a greedy algorithm, GreedyPlus, for IIN alignment, combining data from diverse sources, including network, protein and binding site properties, to identify putative orthologous relationships between interfaces in available worm and yeast data. GreedyPlus is fast and simple, allowing for easy customization of behaviour, yet still capable of generating biologically meaningful network alignments.