Computational analysis of multimorbidity between asthma, eczema and rhinitis

Background: The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes t...

Descripción completa

Detalles Bibliográficos
Autores: Aguilar, Daniel, Pinart, Mariona, Benet, Marta, García Aymerich, Judith, González Ruiz, Juan Ramón, Guerra, Stefano, Kogevinas, Manolis, Sunyer Deu, Jordi, Valverde, Sergi, Oliva Miguel, Baldomero, Antó i Boqué, Josep Maria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/33179
Acceso en línea:http://hdl.handle.net/10230/33179
http://dx.doi.org/10.1371/journal.pone.0179125
Access Level:acceso abierto
Palabra clave:Asthma/epidemiology
Asthma/etiology
Asthma/metabolism
Biomarkers
Comorbidity
Computer Simulation
Databases, Factual
Gene Expression Regulation
Models, Statistical
Models, Theoretical
Proteomics/methods
Rhinitis/epidemiology
Rhinitis/etiology
Rhinitis/metabolism
Proteome
Rhinitis, Allergic/epidemiology
Rhinitis, Allergic/etiology
Rhinitis, Allergic/metabolism
Signal Transduction
Descripción
Sumario:Background: The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them. Methods: An in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins. Results: Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, including IL4 signaling and GATA3-related pathways. A number of proteins potentially associated to these multimorbidity processes were also obtained. Conclusions: These results strongly support the existence of an allergic multimorbidity cluster between asthma, eczema and rhinitis, and suggest that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases. Furthermore, we identified new candidates contributing to multimorbidity that may assist in identifying new targets for multimorbid allergic diseases.