Abstract
One important challenge in the post-genomic era is uncovering the relationships among distinct pathophenotypes by using molecular signatures. Given the complex functional interdependencies between cellular components, a disease is seldom the consequence of a defect in a single gene product, instead reflecting the perturbations of a group of closely related gene products that carry out specific functions together. Therefore, it is meaningful to explore how the community of protein complexes impacts disease associations. Here, by integrating a large amount of information from protein complexes and the cellular basis of diseases, we built a human disease network in which two diseases are linked if they share common disease-related protein complex. A systemic analysis revealed that linked disease pairs exhibit higher comorbidity than those that have no links, and that the stronger association two diseases have based on protein complexes, the higher comorbidity they are prone to display. Moreover, more connected diseases tend to be malignant, which have high prevalence. We provide novel disease associations that cannot be identified through previous analysis. These findings will potentially provide biologists and clinicians new insights into the etiology, classification and treatment of diseases.
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Acknowledgements
This research was supported by the National Natural Science Foundation of China (grant nos. 31100948, 30871394 and 91029717), the National Science Foundation of Heilongjiang Province (grant nos. D201114, QC2009C23), the Science Foundation of Educational Commission of Heilongjiang Province (grant no. 11551233), the Graduate Innovation Fund of Heilongjiang Province (grant nos. YJSCX2011-334HLJ and YJSCX2009-226HLJ).
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Wang, Q., Liu, W., Ning, S. et al. Community of protein complexes impacts disease association. Eur J Hum Genet 20, 1162–1167 (2012). https://doi.org/10.1038/ejhg.2012.74
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DOI: https://doi.org/10.1038/ejhg.2012.74
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