MOSES: A New Approach to Integrate Interactome Topology and Functional Features for Disease Gene Prediction

Disease gene prediction is to date one of the main computational challenges of precision medicine. It is still uncertain if disease genes have unique functional properties that distinguish them from other non-disease genes or, from a network perspective, if they are located randomly in the interacto...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Manuela Petti, Lorenzo Farina, Federico Francone, Stefano Lucidi, Amalia Macali, Laura Palagi, Marianna De Santis
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
Acceso en línea:https://doaj.org/article/2502c2f80ca84500b21f69315cd1c0ac
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Disease gene prediction is to date one of the main computational challenges of precision medicine. It is still uncertain if disease genes have unique functional properties that distinguish them from other non-disease genes or, from a network perspective, if they are located randomly in the interactome or show specific patterns in the network topology. In this study, we propose a new method for disease gene prediction based on the use of biological knowledge-bases (gene-disease associations, genes functional annotations, etc.) and interactome network topology. The proposed algorithm called MOSES is based on the definition of two somewhat opposing sets of genes both disease-specific from different perspectives: warm seeds (i.e., disease genes obtained from databases) and cold seeds (genes far from the disease genes on the interactome and not involved in their biological functions). The application of MOSES to a set of 40 diseases showed that the suggested putative disease genes are significantly enriched in their reference disease. Reassuringly, known and predicted disease genes together, tend to form a connected network module on the human interactome, mitigating the scattered distribution of disease genes which is probably due to both the paucity of disease-gene associations and the incompleteness of the interactome.