Song, B. and Lee, H. (2012) Prioritizing Disease Genes by Integrating Domain Interactions and Disease Mutations in a Protein-Protein Interaction Network,IJICIC, 8(2), 1327-1338

Prioritizing Disease Genes by Integrating Domain Interactions and Disease Mutations in a Protein-Protein Interaction Network

Abstract

Complex diseases such as cancer are involved in inter-relationship amongseveral genes, with protein-protein interaction networks being extensively studied in at-tempts to reveal the relationship between genes and diseases. Although these studies haveshown promising results for identifying disease genes, it is not systemically studied that aprotein functions differently depending on its interaction partners in the network since aprotein can have multiple functions. In this study, domains are considered as functionalunits of proteins and we investigate how disease-related mutations in domains can be usedto identify other disease genes in a domain-domain interaction network. We subsequentlypropose a computational method to predict disease genes based on the following two as-sumptions. The first assumption is that proteins closely interacting with known diseaseproteins in a protein interaction network are likely to be involved in the same disease.Second, although two proteins are in the same distance from known disease genes in aprotein interaction network, the protein interacting with known disease genes through adomain with mutation is more likely to be related to the disease than other proteins thatinteract through domains with no mutation. As a result, when the proposed approach isapplied to five diseases, it highly ranks disease-related genes compared to a model usingonly a protein interaction data set.

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