干扰素信号传导通路和其基因组多态性网络模型的建立.pdf

HEREDITAS (Beijing) 2008 6 , 30(6): 788―794 ISSN 0253-9772 研究报告 DOI: 10.3724/SP.J.1005.2008.00788 崔建军, 田庚善, 田地, 曾争 , 100034 摘要: 通过检索 Pubmed 、Embase 数据库, 整合文献资料, 运用 Teranode Design Suite(TDS) 生物软件, 建立干扰 素(IFN)发挥生物学作用的信号传导通路。应用 SNP Trawler 软件搜索通路中相关基因的 SNP 信息, 并以属性形 式在通路模型中给以显示。结果构建了融合基因的遗传信息尤其是 SNP 相关信息的 IFN 发挥生物学作用的信 号传导通路的网络模型, 此模型共包含JAK-STAT, MAPK-p38 和 PI3K 3 条主要传导通路, 干扰素通过不同的信 号传导通路发挥不同的生物活性, 其中Ⅰ型干扰素通过这 3 条通路发挥抗病毒、抗细胞增殖及免疫调节等重要 作用, 而Ⅱ型干扰素则通过 JAK-STAT 和 MAPK-p38 路径发挥生物学作用, Ⅲ型干扰素则仅通过 PI3K 通路发 挥生物学作用; 这 3 条传导通路包含 98 个基因和 19 693 个 SNPs, 组成了复杂的基因间相互作用网络。此通路 模型的成功建立, 一方面为研究 SNP 对 IFN 生物学作用的影响而预测IFN 疗效提供理论基础, 另一方面为实现 个体化诊疗、发现新的药物作用靶点及开发新的药物奠定基础。 关键词: 干扰素; 信号传导通路; 基因多态性; 模型 An integrated biological model for interferon signaling pathway and its gene polymorphisms CUI Jian-Jun, TIAN Geng-Shan, TIAN Di, ZENG Zheng Department of Infectious Disease, Peking University First Hospital, Beijing 100034, China Abstract: To construct a systemic structural model for interferon (IFN) signaling pathways with gene’s single nucleotide polymorphisms (SNPs) information, it is visual to investigate the effects of gene-gene interaction on IFN signaling path- ways. The genes function information was retrieved from Pubmed and Embase database. The IFN signaling pathways were constructed by applying Teranode Design Suite (TDS) biological software. The SNPs information of genes in pathways was retrieved by using SNP Trawler biological software. The biological systemic structural model for IFN signaling pathways, involving in genetic information, particularly their SNPs information, was constructed successfully. It contained JAK-STAT, MAPK-p38 and PI3K pathways, through which IFNs play variable biological