title: Relationships between predicted moonlighting proteins, human diseases, and comorbidities from a network perspective.
abstract: 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 (i) 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.
authors.affiliation: INSERM, UMR_S1090 TAGC Marseille, France ; Aix-Marseille Université, UMR_S1090, TAGC Marseille, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zanzoni
authors.affiliation: INSERM, UMR_S1090 TAGC Marseille, France ; Aix-Marseille Université, UMR_S1090, TAGC Marseille, France.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Chapple
authors.affiliation: INSERM, UMR_S1090 TAGC Marseille, France ; Aix-Marseille Université, UMR_S1090, TAGC Marseille, France ; Centre National de la Recherche Scientifique Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Brun
keywords: disease comorbidity; human disease; moonlighting proteins; multifunctional proteins; protein-protein interactions