College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Eur J Hum Genet. 2011 Jul;19(7):783-8. doi: 10.1038/ejhg.2011.30. Epub 2011 Mar 9.
The human disease network (HDN) has become a powerful tool for revealing disease-disease associations. Some studies have shown that genes that share similar or same disease phenotypes tend to encode proteins that interact with each other. Therefore, protein-protein interactions (PPIs) may help us to further understand the relationships between diseases with overlapping clinical phenotypes. In this study, we constructed the expanded HDN (eHDN) by combining disease gene information with PPI information, and analyzed its topological features and functional properties. We found that the network is hierarchical and, most diseases are connected to only a few diseases, whereas a small part of diseases are linked to many different diseases. Diseases in a specific disease class tend to cluster together, and genes associated with the same disease are functionally related. Comparing the eHDN with the original HDN (oHDN, constructed using disease gene information) revealed high consistency over all topological and functional properties. This, to some extent, indicates that our eHDN is reliable. In the eHDN, we found some new associations among diseases resulting from the shared genes interacting with disease genes. The new eHDN will provide a valuable reference for clinicians and medical researchers.
人类疾病网络（HDN）已成为揭示疾病-疾病关联的有力工具。一些研究表明，具有相似或相同疾病表型的基因往往编码相互作用的蛋白质。因此，蛋白质-蛋白质相互作用（PPIs）可能有助于我们进一步理解具有重叠临床表型的疾病之间的关系。在这项研究中，我们通过将疾病基因信息与 PPI 信息相结合，构建了扩展的 HDN（eHDN），并分析了其拓扑特征和功能特性。我们发现该网络具有层次结构，大多数疾病仅与少数几种疾病相关联，而一小部分疾病与许多不同的疾病相关联。特定疾病类别中的疾病往往聚集在一起，与同一疾病相关的基因在功能上是相关的。将 eHDN 与原始的 HDN（oHDN，使用疾病基因信息构建）进行比较，在所有拓扑和功能特性上都具有高度一致性。这在一定程度上表明我们的 eHDN 是可靠的。在 eHDN 中，我们发现了一些由于共享基因与疾病基因相互作用而导致的疾病之间的新关联。新的 eHDN 将为临床医生和医学研究人员提供有价值的参考。
