Abstract
BackgroundThe protein-protein interaction (PPI) is one of the most important features to understand biological processes. For a PPI, the physical domain-domain interaction (DDI) plays the key role for biology functions. In the post-genomic era, to rapidly identify homologous PPIs for analyzing the contact residue pairs of their interfaces within DDIs on a genomic scale is essential to determine PPI networks and the PPI interface evolution across multiple species.ResultsIn this study, we proposed "pair Position Specific Scoring Matrix (pairPSSM)" to identify homologous PPIs. The pairPSSM can successfully distinguish the true protein complexes from unreasonable protein pairs with about 90% accuracy. For the test set including 1,122 representative heterodimers and 2,708,746 non-interacting protein pairs, the mean average precision and mean false positive rate of pairPSSM were 0.42 and 0.31, respectively. Moreover, we applied pairPSSM to identify ~450,000 homologous PPIs with their interacting domains and residues in seven common organisms (e.g. Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Escherichia coli).ConclusionsOur pairPSSM is able to provide statistical significance of residue pairs using evolutionary profiles and a scoring system for inferring homologous PPIs. According to our best knowledge, the pairPSSM is the first method for searching homologous PPIs across multiple species using pair position specific scoring matrix and a 3D dimer as the template to map interacting domain pairs of these PPIs. We believe that pairPSSM is able to provide valuable insights for the PPI evolution and networks across multiple species.
Highlights
The protein-protein interaction (PPI) is one of the most important features to understand biological processes
Our method infers ~450,000 homologous PPIs in which the interacting domains and residues are automatically modelled. Based on these homologous PPIs, we believe that pairPSSM is able to provide valuable insights for PPI evolution and networks across multiple species
The pairPSSM is verified in two data sets: (1) we examined whether the energy calculated from pairPSSM could distinguish the true protein complexes and unreasonable protein pairs; (2) for identified homologous PPIs in yeast proteome through pairPSSM, we used two common metrics (i.e. mean average precision (MAP) and mean false positive rate (MFP)) to assess the performance and compared with the empirical matrix used by previous method
Summary
The protein-protein interaction (PPI) is one of the most important features to understand biological processes. For a PPI, the physical domain-domain interaction (DDI) plays the key role for biology functions. Many biological processes involve different types of interactions among proteins. Systematic identification of protein-protein interactions (PPIs) had been proposed by high throughput experimental methods (e.g. large scale yeast two-hybrid analysis and tandem affinity purification) and computational methods (e.g. phylogenetic profiles [2], gene expression profiles [3], known three-dimensional (3D) complexes [4], and interologs mapping [5]). The protein pair of Rix7p and Shp1p should be not a homologous PPI of p47 and p97 due to lack of the interacting domains
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