4.6 Article

Relationships between predicted moonlighting proteins, human diseases, and comorbidities from a network perspective

Journal

FRONTIERS IN PHYSIOLOGY
Volume 6, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2015.00171

Keywords

moonlighting proteins; human disease; protein-protein interactions; multifunctional proteins; disease comorbidity

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Funding

  1. Aix-Marseille University
  2. Centre National de la Recherche Scientifique(CNRS)
  3. Institut National de la Sante et de la Recherche Medicale(Inserm)
  4. [A12171AS]

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Moonlighting proteins are a subset of multifunctional proteins characterized by their multiple, independent, and unrelated biological functions. We recently set up a large-scale identification of moonlighting proteins using a protein-protein interaction (PPI) network approach. We established that 3% of the current human interactome is composed of predicted moonlighting proteins. We found that disease-related genes are over-represented among those candidates. Here, by comparing moonlighting candidates to non-candidates as groups, we further show that (7 they are significantly involved in more than one disease, (ii) they contribute to complex rather than monogenic diseases, (iii) the diseases in which they are involved are phenotypically different according to their annotations, finally, (iv) they are enriched for diseases pairs showing statistically significant comorbidity patterns based on Medicare records. Altogether, our results suggest that some observed comorbidities between phenotypically different diseases could be due to a shared protein involved in unrelated biological processes.

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