SPINAL: scalable protein interaction network alignment

Motivation: Given protein-protein interaction (PPI) networks of a pair of species, a pairwise global alignment corresponds to a one-to-one mapping between their proteins. Based on the presupposition that such a mapping provides pairs of functionally orthologous proteins accurately, the results of the alignment may then be used in comparative systems biology problems such as function prediction/verification or construction of evolutionary relationships. Results: We show that the problem is NP-hard even for the case where the pair of networks are simply paths. We next provide a polynomial time heuristic algorithm, SPINAL, which consists of two main phases. In the first coarse-grained alignment phase, we construct all pairwise initial similarity scores based on pairwise local neighborhood matchings. Using the produced similarity scores, the fine-grained alignment phase produces the final one-to-one mapping by iteratively growing a locally improved solution subset. Both phases make use of the construction of neighborhood bipartite graphs and the contributors as a common primitive. We assess the performance of our algorithm on the PPI networks of yeast, fly, human and worm. We show that based on the accuracy measures used in relevant work, our method outperforms the state-of-the-art algorithms. Furthermore, our algorithm does not suffer from scalability issues, as such accurate results are achieved in reasonable running times as compared with the benchmark algorithms.