基于通路串扰分析的阿尔茨海默症致病机理探寻

Pathogenesis Exploration of Alzheimer’s Disease Based on Pathway Crosstalk Analysis

目前特征基因提取及致病信号传导通路的重构已成为探寻重大疾病致病机理的重要手段。考虑到基因之间的关联性,利用互信息（mutual information,MI）算法提取出AD患病及其健康对照样本中关联度具有明显变化的基因作为特征基因,在此基础上,基于KEGG通路分析获取特征基因所涉及的信号传导通路,利用距离相关性（distance correlation,DC）算法度量它们之间的串扰关系,最终探寻到33对AD患病前后串扰关系变化较大的通路。通过生物学分析得到：慢性粒细胞白血病通路和剪接体相关通路、子宫内膜癌通路和霍乱弧菌感染通路、幽门螺杆菌感染的上皮细胞传导通路和嘧啶代谢通路,以及促性腺激素通路和嘧啶代谢等通路间的串扰及特征基因的显著变化对AD的发生和发展具有重要的推动作用,研究成果为探寻AD的致病机理提供了新的思路及有益的支撑。

Recently, the extraction of characteristic genes and the reconstruction of pathogenic signal transduction pathways have become an important means to explore the pathogenesis of many diseases. Considering the association between genes, mutual information （MI） algorithm is applied to extract the genes with significant changes in association between AD and the healthy samples Based on that, signal transduction pathways were obtained based on KEGG pathway analysis. Then, distance correlation （DC） algorithm was used to measure the crosstalks between them. Finally, 33 pairs of pathways were found to have larger changes in crosstalk. The biological analysis show that, the crosstalk between Chronic myeloid leukemia and Spliceosome, Endometrial cancer and Vibrio cholerae infection, Epithelial cell signaling in Helicobacter pylori infection and Pyrimidine metabolism, GnRH signaling pathway and Pyrimidine metabolism, as well as the significant changes of characteristic genes play important roles in the onset and development of AD. Our method provide a new and efficient way to explore the pathogenesis of AD.