期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：35
页码：12763-12768
DOI：10.1073/pnas.0806627105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Protein-protein interactions (PPIs) and their networks play a central role in all biological processes. Akin to the complete sequencing of genomes and their comparative analysis, complete descriptions of interactomes and their comparative analysis is fundamental to a deeper understanding of biological processes. A first step in such an analysis is to align two or more PPI networks. Here, we introduce an algorithm, IsoRank, for global alignment of multiple PPI networks. The guiding intuition here is that a protein in one PPI network is a good match for a protein in another network if their respective sequences and neighborhood topologies are a good match. We encode this intuition as an eigenvalue problem in a manner analogous to Google's PageRank method. Using IsoRank, we compute a global alignment of the Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, and Homo sapiens PPI networks. We demonstrate that incorporating PPI data in ortholog prediction results in improvements over existing sequence-only approaches and over predictions from local alignments of the yeast and fly networks. Previous methods have been effective at identifying conserved, localized network patterns across pairs of networks. This work takes the further step of performing a global alignment of multiple PPI networks. It simultaneously uses sequence similarity and network data and, unlike previous approaches, explicitly models the tradeoff inherent in combining them. We expect IsoRank--with its simultaneous handling of node similarity and network similarity--to be applicable across many scientific domains.
