한빛사논문
Abstract
Solip Park1, Jae-Seong Yang1, Young-Eun Shin2, Juyong Park3, Sung Key Jang1,2,4,5 and Sanguk Kim1,2,6,*
1 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea, 2 Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea, 3 Physics Department, Kyung Hee University, Seoul, Korea, 4 Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang, Korea, 5 Biotechnology Research Center, Pohang University of Science and Technology, Pohang, Korea and 6 Division of IT Convergence Engineering, Pohang University of Science and Technology, Pohang, Korea
* Corresponding author. Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea. Tel.: +82 54 279 2348;Fax: +82 54 279 2199
Proteins targeting the same subcellular localization tend to participate in mutual protein.protein interactions (PPIs) and are often functionally associated. Here, we investigated the relationship between disease-associated proteins and their subcellular localizations, based on the assumption that protein pairs associated with phenotypically similar diseases are more likely to be connected via subcellular localization. The spatial constraints from subcellular localization significantly strengthened the disease associations of the proteins connected by subcellular localizations. In particular, certain disease types were more prevalent in specific subcellular localizations. We analyzed the enrichment of disease phenotypes within subcellular localizations, and found that there exists a significant correlation between disease classes and subcellular localizations. Furthermore, we found that two diseases displayed high comorbidity when disease-associated proteins were connected via subcellular localization. We newly explained 7584 disease pairs by using the context of protein subcellular localization, which had not been identified using shared genes or PPIs only. Our result establishes a direct correlation between protein subcellular localization and disease association, and helps to understand the mechanism of human disease
progression.
Molecular Systems Biology 7: 494; published online 24 May 2011; doi:10.1038/msb.2011.29
Subject Categories: metabolic and regulatory networks; molecular biology of disease
Keywords: cellular networks; comorbidity; human disease; subcellular localization
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