Grosdidier Solène, Ferrer Antoni, Faner Rosa, Piñero Janet, Roca Josep, Cosío Borja, Agustí Alvar, Gea Joaquim, Sanz Ferran, Furlong Laura I
Respir Res. 2014 Sep 24;15(1):111. doi: 10.1186/s12931-014-0111-4.
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.
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.
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.
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.
慢性阻塞性肺疾病（COPD）患者常伴有其他疾病，这些疾病会显著恶化他们的健康状况和生命预后。COPD合并多种疾病的致病机制尚未完全明确，因此探索COPD与其相关疾病之间潜在的分子和生物学联系备受关注。
我们开发了一种新颖的、无偏倚的、整合网络医学方法，用于分析疾病组、相互作用组、生物途径和烟草烟雾暴露组，并将其应用于临床专家确定的16种常见COPD合并症的研究。
我们的分析表明，此处研究的所有COPD合并症在分子和生物学水平上均相关，共享基因、蛋白质和生物途径。通过更详细地检查COPD与其相关疾病的联系，我们确定了COPD中已知的生物途径，如炎症、内皮功能障碍或细胞凋亡，这为该方法提供了概念验证。更有趣的是，我们发现了以前被忽视的可能有助于解释COPD合并症的生物途径，如除心血管疾病外的COPD合并症中的止血途径，以及COPD与抑郁症关联中的细胞周期途径。此外，我们还在途径水平上观察到COPD合并症之间的相似性，提示不同COPD合并症存在共同的生物学机制。最后，烟草烟雾中的化学物质平均靶向69%参与COPD合并症的已鉴定蛋白质。
本文提出的网络医学方法能够识别COPD与合并疾病之间可能的分子联系，并表明其中许多是烟草暴露组的靶点，为理解COPD合并症的分子基础提出了新的研究领域。
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