Harbin Institute of Technology Shenzhen Graduate School, Shenzhen 518055, China.
Lab of Epigenetics and Advanced Health Technology, Space Science and Technology Institute (Shenzhen), Shenzhen 518117, China.
Genes (Basel). 2020 Jul 7;11(7):754. doi: 10.3390/genes11070754.
Docosahexaenoic acid (DHA) is effective in the prevention and treatment of cancer, congenital disorders, and various chronic diseases. According to the omnigenic hypothesis, these complex diseases are caused by disordered gene regulatory networks comprising dozens to hundreds of core genes and a mass of peripheral genes. However, conventional research on the disease intervention mechanism of DHA only focused on specific types of genes or pathways instead of examining genes at the network level, resulting in conflicting conclusions. In this study, we used HotNet2, a heat diffusion kernel algorithm, to calculate the gene regulatory networks of connectivity map (cMap)-derived agents (including DHA) based on gene expression profiles, aiming to interpret the disease intervention mechanism of DHA at the network level. As a result, significant gene regulatory networks for DHA and 676 cMap-derived agents were identified respectively. The biological functions of the DHA-regulated gene network provide preliminary insights into the mechanism by which DHA intervenes in disease. In addition, we compared the gene regulatory networks of DHA with those of cMap-derived agents, which allowed us to predict the pharmacological effects and disease intervention mechanism of DHA by analogy with similar agents with clear indications and mechanisms. Some of our analysis results were supported by experimental observations. Therefore, this study makes a significant contribution to research on the disease intervention mechanism of DHA at the regulatory network level, demonstrating the potential application value of this methodology in clarifying the mechanisms about nutrients influencing health.
二十二碳六烯酸（DHA）在癌症、先天疾病和各种慢性疾病的预防和治疗方面具有显著效果。根据全基因组假说，这些复杂疾病是由几十个到几百个核心基因和大量外围基因组成的紊乱基因调控网络引起的。然而，传统的 DHA 疾病干预机制研究仅关注特定类型的基因或途径，而不是在网络层面上检查基因，导致结论相互矛盾。在这项研究中，我们使用热扩散核算法（HotNet2），根据基因表达谱计算连接图谱（cMap）衍生药物（包括 DHA）的基因调控网络，旨在从网络层面解释 DHA 的疾病干预机制。结果分别确定了 DHA 和 676 个 cMap 衍生药物的显著基因调控网络。DHA 调控基因网络的生物学功能为 DHA 干预疾病的机制提供了初步见解。此外，我们比较了 DHA 的基因调控网络与 cMap 衍生药物的基因调控网络，使我们能够通过类比具有明确适应症和机制的类似药物来预测 DHA 的药理作用和疾病干预机制。我们的一些分析结果得到了实验观察的支持。因此，这项研究在调控网络层面上对 DHA 的疾病干预机制研究做出了重要贡献，证明了该方法在阐明营养物质对健康影响的机制方面具有潜在的应用价值。
