Identifying synergistic therapeutic targets in RA using systems biology

利用系统生物学确定 RA 的协同治疗靶点

• 批准号: 9164023
• 负责人: GARY S FIRESTEIN
• 金额: $ 20.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9164023
• 关键词: Affect; Arthritis; Behavioral Mechanisms; Biological Assay; Cartilage Matrix; Cell Adhesion; Cell Line; Cells; Computer Simulation; DNA Methylation; Data; Data Set; Disease; Drug Targeting; Environmental Risk Factor; Epigenetic Process; Fibroblasts; Gene Expression; Gene Expression Regulation; Gene Proteins; Genes; Genetic; Immune response; Invaded; Joints; Light; Measures; Mesenchymal; Methods; Modeling; Molecular Profiling; Network-based; Normal Cell; Pathogenesis; Pathway interactions; Patients; Pattern; Phenotype; Play; Regulation; Rheumatoid Arthritis; Role; Synovitis; Systems Biology; Testing; Therapeutic; Training; Work; abstracting; base; computer based statistical methods; effective therapy; experience; imprint; improved; joint destruction; joint injury; knock-down; network models; new therapeutic target; novel; research study; risk variant; therapeutic target; transcriptome sequencing; transcriptomics; tumor

Abstract Joint damage and synovial inflammation in rheumatoid arthritis (RA) are influenced by genetic and environmental factors. In our previous studies, we have identified a panel of genes and pathways that could be targeted for RA by integrating DNA methylation data with transcriptomics and RA risk gene data. Built upon these results, we will construct a gene network composed of RA relevant genes whose expression profiles represent RA pathogenesis. We will develop a novel systems biology method to search for synergistic therapeutic targets in this gene network. Once completed, this proposed work will not only identify drug targets for effective treatment of RA but also shed light into understanding the regulatory mechanisms of disease formation.

抽象的 类风湿性关节炎 (RA) 的关节损伤和滑膜炎症受遗传影响 和环境因素。在我们之前的研究中，我们已经鉴定了一组基因 通过将 DNA 甲基化数据与 转录组学和 RA 风险基因数据。基于这些结果，我们将构建一个基因 由 RA 相关基因组成的网络，其表达谱代表 RA 发病机制。 我们将开发一种新的系统生物学方法来寻找协同治疗靶点 这个基因网络。一旦完成，这项拟议的工作不仅将确定药物靶标 RA 的有效治疗，同时也有助于理解 RA 的调节机制 疾病的形成。