Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. It is likely that comparison and alignment of biological networks will similarly revolutionize our understanding of biological systems . Existing network alignments are based largely upon information external to the networks, such as sequence, because  purely topological alignment of large, noisy networks is a theoretically challenging problem that has yet to be solved . In this paper, we present the first alignments of large networks based solely upon detailed network topology, and demonstrate that both species phylogeny (the ``tree of life'') and detailed biological function of individual proteins can be extracted from topological comparisons of biological networks. Our phylogenetic trees provide a new and independent source of phylogenetic information. Our alignments are large, dense, and contiguous, suggesting functional predictions of hundreds of currently unannotated proteins. Finally, our alignment of the protein-protein interaction network of two very different species--yeast and human--indicate that even distant species share a surprising amount of network topology with each other, suggesting that there may be broad similarities in internal cellular wiring across all life on Earth.
Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact . Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised . In this paper, we present by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from a solely topological comparison of networks. Topological alignments provide an independent new source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species--yeast and human--indicate that even distant species share a surprising amount of network topology with each other, suggesting broad similarities in internal cellular wiring across all life on Earth.
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