Proteins do not carry out their functions alone. Instead, they often act by participating in macromolecular complexes and play different functional roles depending on the other members of the complex. It is therefore interesting to identify co-complex relationships. Although protein complexes can be identified in a high-throughput manner by experimental technologies such as affinity purification coupled with mass spectrometry (APMS), these large-scale datasets often suffer from high false positive and false negative rates. Here, we present a computational method that predicts co-complexed protein pair (CCPP) relationships using kernel methods from heterogeneous data sources. We show that a diffusion kernel based on random walks on the full network topology yields good performance in predicting CCPPs from protein interaction networks. In the setting of direct ranking, a diffusion kernel performs much better than the mutual clustering coefficient. In the setting of SVM classifiers, a diffusion kernel performs much better than a linear kernel. We also show that combination of complementary information improves the performance of our CCPP recognizer. A summation of three diffusion kernels based on two-hybrid, APMS, and genetic interaction networks and three sequence kernels achieves better performance than the sequence kernels or diffusion kernels alone. Inclusion of additional features achieves a still better ROC(50) of 0.937. Assuming a negative-to-positive ratio of 600ratio1, the final classifier achieves 89.3% coverage at an estimated false discovery rate of 10%. Finally, we applied our prediction method to two recently described APMS datasets. We find that our predicted positives are highly enriched with CCPPs that are identified by both datasets, suggesting that our method successfully identifies true CCPPs. An SVM classifier trained from heterogeneous data sources provides accurate predictions of CCPPs in yeast. This computational method thereby provides an inexpensive method for identifying protein complexes that extends and complements high-throughput experimental data.
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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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Evidence ID | Analyze ID | File | Description |
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