Traditional approaches for homology detection rely on finding sufficient similarities between protein sequences. Motivated by studies demonstrating that from non-sequence based sources of biological information, such as the secondary or tertiary molecular structure, we can extract certain types of biological knowledge when sequence-based approaches fail, we hypothesize that protein-protein interaction (PPI) network topology and protein sequence might give insights into different slices of biological information. Since proteins aggregate to perform a function instead of acting in isolation, analyzing complex wirings around a protein in a PPI network could give deeper insights into the protein's role in the inner working of the cell than analyzing sequences of individual genes. Hence, we believe that one could lose much information by focusing on sequence information alone. We examine whether the information about homologous proteins captured by PPI network topology differs and to what extent from the information captured by their sequences. We measure how similar the topology around homologous proteins in a PPI network is and show that such proteins have statistically significantly higher network similarity than nonhomologous proteins. We compare these network similarity trends of homologous proteins with the trends in their sequence identity and find that network similarities uncover almost as much homology as sequence identities. Although none of the two methods, network topology and sequence identity, seems to capture homology information in its entirety, we demonstrate that the two might give insights into somewhat different types of biological information, as the overlap of the homology information that they uncover is relatively low. Therefore, we conclude that similarities of proteins' topological neighborhoods in a PPI network could be used as a complementary method to sequence-based approaches for identifying homologs, as well as for analyzing evolutionary distance and functional divergence of homologous proteins.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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