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Título:	From comorbidities of chronic obstructive pulmonary disease to identification of shared molecular mechanisms by data integration
Autor/a:	Gomez Cabrero, David; Menche, Jörg; Vargas, Claudia; Cano Franco, Isaac; Maier, Dieter; Barabási, Albert László; Tegnér, Jesper; Roca Torrent, Josep; Synergy‐COPD consortium
Notas:	Background: Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. Results: Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity. We integrated records from approximately 13 M patients from the Medicare database with disease-gene maps that we derived from several resources including a semantic-derived knowledge-base. Using rank-based statistics we not only recovered known comorbidities but also discovered a novel association between COPD and digestive diseases. Furthermore, our analysis provides the first set of COPD co-morbidity candidate biomarkers, including IL15, TNF and JUP, and characterizes their association to aging and life-style conditions, such as smoking and physical activity. Conclusions: The developed framework provides novel insights in COPD and especially COPD co-morbidity associated mechanisms. The methodology could be used to discover and decipher the molecular underpinning of other comorbidity relationships and furthermore, allow the identification of candidate co-morbidity biomarkers
Materia(s):	-Malalties pulmonars obstructives cròniques -Comorbiditat -Mineria de dades -Marcadors bioquímics -Malalties de l'aparell digestiu -Bioinformàtica -Chronic obstructive pulmonary diseases -Comorbidity -Data mining -Biochemical markers -Digestive system diseases -Bioinformatics
Derechos:	cc-by (c) Gomez-Cabrero, David et al., 2016 http://creativecommons.org/licenses/by/3.0/es
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	BioMed Central
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