Human Pathway-Based Disease Network
Human Pathway-Based Disease Network
复制标题
基于人类通路的疾病网络
DOI：
10.1109/tcbb.2017.2774802
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gao Lin
中科院分区：
文献类型：
--
作者：
Yu Liang;Gao Lin
构建疾病-疾病相似网络对于阐明疾病起源与分子机制之间的联系，以及研究疾病功能和医学研究具有重要意义。在本文中，我们利用高质量的蛋白质相互作用网络和一系列通路数据库构建了一个基于人类通路的疾病网络（Human pathway -based Disease network， HPDN），以探索疾病与其内在相互作用之间的关系。我们发现两种疾病的相似性与其共享功能通路的数量和相关基因集之间的相互作用有很强的相关性。将HPDN与分别基于基因和症状的疾病网络进行比较，我们发现这三个网络有很高的重叠率。此外，HPDN可以预测新的疾病-疾病相关性，这得到了比较毒物基因组学数据库（CTD）基准和大型生物医学文献数据库的支持。基于途径的疾病之间的全面、高质量关系可以进一步应用于研究系统医学中的重要问题，例如药物再利用。基于我们网络中的密集子图，我们发现强的松和叶酸两种药物可能有新的适应症，这将为复杂疾病的治疗提供潜在的方向。
Constructing disease-disease similarity network is important in elucidating the associations between the origin and molecular mechanism of diseases, and in researching disease function and medical research. In this paper, we use a high-quality protein interaction network and a collection of pathway databases to construct a Human Pathway-based Disease Network (HPDN) to explore the relationship between diseases and their intrinsic interactions. We find that the similarity of two diseases has a strong correlation with the number of their shared functional pathways and the interaction between their related gene sets. Comparing HPDN with disease networks based on genes and symptoms respectively, we find the three networks have high overlap rates. Additionally, HPDN can predict new disease-disease correlations, which are supported by Comparative Toxicogenomics Database (CTD) benchmark and large-scale biomedical literature database. The comprehensive, high-quality relations between diseases based on pathways can further be applied to study important matters in systems medicine, for instance, drug repurposing. Based on a dense subgraph in our network, we find two drugs, prednisone and folic acid, may have new indications, which will provide potential directions for the treatments of complex diseases.