SysBioLab, Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal.
Department of Biomedicine, University of Basel, Basel, Switzerland.
Sci Rep. 2017 Jul 12;7(1):5216. doi: 10.1038/s41598-017-05224-0.
Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although HD is monogenic, its molecular manifestation appears highly complex and involves multiple cellular processes. The recent application of high throughput platforms such as microarrays and mass-spectrometry has indicated multiple pathogenic routes. The massive data generated by these techniques together with the complexity of the pathogenesis, however, pose considerable challenges to researchers. Network-based methods can provide valuable tools to consolidate newly generated data with existing knowledge, and to decipher the interwoven molecular mechanisms underlying HD. To facilitate research on HD in a network-oriented manner, we have developed HDNetDB, a database that integrates molecular interactions with many HD-relevant datasets. It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). HDNetDB is publicly accessible at http://hdnetdb.sysbiolab.eu .
亨廷顿病(HD)是一种由亨廷顿基因中 CAG 重复扩增引起的进行性和致命的神经退行性疾病。尽管 HD 是单基因疾病,但它的分子表现似乎非常复杂,涉及多个细胞过程。最近高通量平台(如微阵列和质谱)的应用表明了多种致病途径。这些技术产生的大量数据以及发病机制的复杂性,给研究人员带来了相当大的挑战。基于网络的方法可以为整合新生成的数据和现有知识提供有价值的工具,并阐明 HD 潜在的分子机制。为了以面向网络的方式促进 HD 的研究,我们开发了 HDNetDB,这是一个整合了分子相互作用和许多与 HD 相关数据集的数据库。它允许用户使用来自人类样本或模式生物的与 HD 相关的基因表达、表型和其他类型的数据,获取、可视化和优先考虑分子相互作用网络。我们通过案例研究说明了 HDNetDB 的几个功能,并确定了构成 HD 和未折叠蛋白反应(UPR)之间潜在串扰的蛋白质。HDNetDB 可在 http://hdnetdb.sysbiolab.eu 上公开访问。