Cargando…

Network medicine analysis of COPD multimorbidities

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer concomitant disorders that worsen significantly their health status and vital prognosis. The pathogenic mechanisms underlying COPD multimorbidities are not completely understood, thus the exploration of potential mol...

Descripción completa

Detalles Bibliográficos
Autores principales: Grosdidier, Solène, Ferrer, Antoni, Faner, Rosa, Piñero, Janet, Roca, Josep, Cosío, Borja, Agustí, Alvar, Gea, Joaquim, Sanz, Ferran, Furlong, Laura I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177421/
https://www.ncbi.nlm.nih.gov/pubmed/25248857
http://dx.doi.org/10.1186/s12931-014-0111-4
_version_ 1782336769754136576
author Grosdidier, Solène
Ferrer, Antoni
Faner, Rosa
Piñero, Janet
Roca, Josep
Cosío, Borja
Agustí, Alvar
Gea, Joaquim
Sanz, Ferran
Furlong, Laura I
author_facet Grosdidier, Solène
Ferrer, Antoni
Faner, Rosa
Piñero, Janet
Roca, Josep
Cosío, Borja
Agustí, Alvar
Gea, Joaquim
Sanz, Ferran
Furlong, Laura I
author_sort Grosdidier, Solène
collection PubMed
description BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer concomitant disorders that worsen significantly their health status and vital prognosis. The pathogenic mechanisms underlying COPD multimorbidities are not completely understood, thus the exploration of potential molecular and biological linkages between COPD and their associated diseases is of great interest. METHODS: We developed a novel, unbiased, integrative network medicine approach for the analysis of the diseasome, interactome, the biological pathways and tobacco smoke exposome, which has been applied to the study of 16 prevalent COPD multimorbidities identified by clinical experts. RESULTS: Our analyses indicate that all COPD multimorbidities studied here are related at the molecular and biological level, sharing genes, proteins and biological pathways. By inspecting the connections of COPD with their associated diseases in more detail, we identified known biological pathways involved in COPD, such as inflammation, endothelial dysfunction or apoptosis, serving as a proof of concept of the methodology. More interestingly, we found previously overlooked biological pathways that might contribute to explain COPD multimorbidities, such as hemostasis in COPD multimorbidities other than cardiovascular disorders, and cell cycle pathway in the association of COPD with depression. Moreover, we also observed similarities between COPD multimorbidities at the pathway level, suggesting common biological mechanisms for different COPD multimorbidities. Finally, chemicals contained in the tobacco smoke target an average of 69% of the identified proteins participating in COPD multimorbidities. CONCLUSIONS: The network medicine approach presented here allowed the identification of plausible molecular links between COPD and comorbid diseases, and showed that many of them are targets of the tobacco exposome, proposing new areas of research for understanding the molecular underpinning of COPD multimorbidities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0111-4) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4177421
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-41774212014-10-02 Network medicine analysis of COPD multimorbidities Grosdidier, Solène Ferrer, Antoni Faner, Rosa Piñero, Janet Roca, Josep Cosío, Borja Agustí, Alvar Gea, Joaquim Sanz, Ferran Furlong, Laura I Respir Res Research BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer concomitant disorders that worsen significantly their health status and vital prognosis. The pathogenic mechanisms underlying COPD multimorbidities are not completely understood, thus the exploration of potential molecular and biological linkages between COPD and their associated diseases is of great interest. METHODS: We developed a novel, unbiased, integrative network medicine approach for the analysis of the diseasome, interactome, the biological pathways and tobacco smoke exposome, which has been applied to the study of 16 prevalent COPD multimorbidities identified by clinical experts. RESULTS: Our analyses indicate that all COPD multimorbidities studied here are related at the molecular and biological level, sharing genes, proteins and biological pathways. By inspecting the connections of COPD with their associated diseases in more detail, we identified known biological pathways involved in COPD, such as inflammation, endothelial dysfunction or apoptosis, serving as a proof of concept of the methodology. More interestingly, we found previously overlooked biological pathways that might contribute to explain COPD multimorbidities, such as hemostasis in COPD multimorbidities other than cardiovascular disorders, and cell cycle pathway in the association of COPD with depression. Moreover, we also observed similarities between COPD multimorbidities at the pathway level, suggesting common biological mechanisms for different COPD multimorbidities. Finally, chemicals contained in the tobacco smoke target an average of 69% of the identified proteins participating in COPD multimorbidities. CONCLUSIONS: The network medicine approach presented here allowed the identification of plausible molecular links between COPD and comorbid diseases, and showed that many of them are targets of the tobacco exposome, proposing new areas of research for understanding the molecular underpinning of COPD multimorbidities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0111-4) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-24 2014 /pmc/articles/PMC4177421/ /pubmed/25248857 http://dx.doi.org/10.1186/s12931-014-0111-4 Text en © Grosdidier et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Grosdidier, Solène
Ferrer, Antoni
Faner, Rosa
Piñero, Janet
Roca, Josep
Cosío, Borja
Agustí, Alvar
Gea, Joaquim
Sanz, Ferran
Furlong, Laura I
Network medicine analysis of COPD multimorbidities
title Network medicine analysis of COPD multimorbidities
title_full Network medicine analysis of COPD multimorbidities
title_fullStr Network medicine analysis of COPD multimorbidities
title_full_unstemmed Network medicine analysis of COPD multimorbidities
title_short Network medicine analysis of COPD multimorbidities
title_sort network medicine analysis of copd multimorbidities
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177421/
https://www.ncbi.nlm.nih.gov/pubmed/25248857
http://dx.doi.org/10.1186/s12931-014-0111-4
work_keys_str_mv AT grosdidiersolene networkmedicineanalysisofcopdmultimorbidities
AT ferrerantoni networkmedicineanalysisofcopdmultimorbidities
AT fanerrosa networkmedicineanalysisofcopdmultimorbidities
AT pinerojanet networkmedicineanalysisofcopdmultimorbidities
AT rocajosep networkmedicineanalysisofcopdmultimorbidities
AT cosioborja networkmedicineanalysisofcopdmultimorbidities
AT agustialvar networkmedicineanalysisofcopdmultimorbidities
AT geajoaquim networkmedicineanalysisofcopdmultimorbidities
AT sanzferran networkmedicineanalysisofcopdmultimorbidities
AT furlonglaurai networkmedicineanalysisofcopdmultimorbidities