Divide, Align and Full-Search for Discovering Conserved Protein Complexes

Advances in modern technologies for measuring protein-protein interaction (PPI) has boosted research in PPI networks analysis and comparison. One of the challenging problems in comparative analysis of PPI networks is the comparison of networks across species for discovering conserved modules. Approaches for this task generally merge the considered networks into one new weighted graph, called alignment graph, which describes how interaction between each pair of proteins is preserved in different networks. The problem of finding conserved protein complexes across species is then transformed into the problem of searching the alignment graph for subnetworks whose weights satisfy a given constraint. Because the latter problem is computationally intractable, generally greedy techniques are used. In this paper we propose an alternative approach for this task. First, we use a technique we recently introduced for dividing PPI networks into small subnets which are likely to contain conserved modules. Next, we perform network alignment on pairs of resulting subnets from different species, and apply an exact search algorithm iteratively on each alignment graph, each time changing the constraint based on the weight of the solution found in the previous iteration. Results of experiments show that this method discovers multiple accurate conserved modules, and can be used for refining state-of-the-art algorithms for comparative network analysis.