Computational analysis of multimorbidity between asthma, eczema and rhinitis.
Computational analysis of multimorbidity between asthma, eczema and rhinitis.
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DOI：
10.1371/journal.pone.0179125
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Antó JM
中科院分区：
文献类型：
--
作者：
Aguilar D;Pinart M;Koppelman GH;Saeys Y;Nawijn MC;Postma DS;Akdis M;Auffray C;Ballereau S;Benet M;García-Aymerich J;González JR;Guerra S;Keil T;Kogevinas M;Lambrecht B;Lemonnier N;Melen E;Sunyer J;Valenta R;Valverde S;Wickman M;Bousquet J;Oliva B;Antó JM
解释哮喘、湿疹和鼻炎（过敏性多发性鼻炎）共存的机制在很大程度上是未知的。我们通过鉴定三种主要过敏性疾病共同的蛋白质和细胞过程，在分子水平上研究了三种主要过敏性疾病之间的多重免疫的机制。基于蛋白质相互作用网络拓扑结构的计算分析进行了计算机模拟研究，以表征哮喘、湿疹和鼻炎的多发病的分子机制。作为第一步，使用数据挖掘方法鉴定与任一疾病相关的蛋白质，并计算它们的重叠。其次，建立了一个功能性相互作用网络，允许识别参与过敏性多药耐药的细胞通路。最后，基于网络的算法生成了一个新预测的多发病相关蛋白质的排名列表。哮喘，湿疹和鼻炎共享的相关蛋白比预期的更多的机会，和他们的相关蛋白表现出显着程度的相互联系的相互作用网络。哮喘、湿疹和鼻炎的多发病机制涉及15条通路，包括IL 4信号通路和GATA 3相关通路。还获得了许多与这些多突变过程潜在相关的蛋白质。这些结果强烈支持哮喘、湿疹和鼻炎之间存在过敏性多发病簇，并表明2型信号通路代表了过敏性疾病的相关多发病机制。此外，我们确定了新的候选人有助于多发病，可能有助于确定新的目标，多发病过敏性疾病。
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. 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. 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. 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.