Protein-protein Interaction Network Analysis And Its Application Of The Comparative Biology,

The activity of cellular life relies on properly functioning of the extremely complex interaction networks among numerous intracellular constituents. One key aim of postgenomic biology is to reconstruct the complete molecular interaction networks within cells and on the basis of that to understand the principles on the construction, function and evolution of life. Recent progresses in high-throughput proteomics have provided us with a first chance to characterize protein interaction networks (PINs), but also raised new challenges in interpreting the accumulating data. As with sequence analysis, a comparative apporoach often provides insights into the underlying laws behind complex phenomena. Motivated by this, we propose a computational strategy NetAlign to enable comparison of two protein interaction networks. NetAlign searches for conserved network substructures (CoNSs) that can pair in two PINs by combining interaction topology and sequence similarity. Using this approach we perform twenty-one pairwise comparisons among the seven recently available PINs of E.coli, H.pylori, S.cerevisiae, C.elegans, D.melanogaster, M.musculus and H.sapiens. We show that beyond what is gleaned from the genome, PIN comparison not only reveals species conservation but also indicates potential species divergence at the PIN level. And the identified CoNSs are known or candidate conserved complexes and can be used to predict PPIs, protein functions and orthologs. To meet the need for comparative tools at the PIN level, we implemented a web-interfaced version of NetAlign. The NetAlign server enables on-line comparison of two large-scale PINs. Furthermore, to facilitate the comparison of multiple PINs, we introduce mNetAlign, a NetAlign-based database designed to enable comparison of PINs across multiple species.