TY - JOUR
T1 - Computational analysis of multimorbidity between asthma, eczema and rhinitis
AU - Aguilar, Daniel
AU - Pinart, Mariona
AU - Koppelman, Gerard H.
AU - Saeys, Yvan
AU - Nawijn, Martijn C.
AU - Postma, Dirkje S.
AU - Akdis, Mubeccel
AU - Auffray, Charles
AU - Ballereau, Stephane
AU - Benet, Marta
AU - Garcõa-Aymerich, Judith
AU - Ramon Gonzalez, Juan
AU - Guerra, Stefano
AU - Keil, Thomas
AU - Kogevinas, Manolis
AU - Lambrecht, Bart
AU - Lemonnier, Nathanael
AU - Melen, Erik
AU - Sunyer, Jordi
AU - Valenta, Rudolf
AU - Valverde, Sergi
AU - Wickman, Magnus
AU - Bousquet, Jean
AU - Oliva, Baldo
AU - Anto, Josep M.
N1 - Publisher Copyright:
© 2017 Aguilar et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0179125
DO - 10.1371/journal.pone.0179125
M3 - Article
C2 - 28598986
AN - SCOPUS:85020891379
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 6
M1 - 0179125
ER -