Figure 1

Schematic representation of the methodology applied in this study. Panel A: Clinical experts selected prevalent multimorbidities in COPD, and manually curated lists of Concept Unique Identifiers (CUI) obtained from the Unified Medical Language System (UMLS) Metathesaurus to extract relevant synonyms for each disease. Panel B: DisGeNet was used to obtain gene-disease associations and every protein encoded by the selected gene was mapped into a protein-protein network created from HIPPIE and Pathway Commons databases. Panel C: Gene-disease associations and protein-protein interaction information were combined to build the diseasome. The Molecular Comorbidity Index estimates the strength of association between 2 diseases based on shared genes and proteins. The genes and proteins targeted by cigarette smoke components were obtained from CTD. Panel D: A functional enrichment analysis was performed to identify the most likely pathways that could lead to the development of a specific multimorbidity and Panel E: pathway similarity between multimorbidities was assessed calculating the Jaccard Coefficient.