中文摘要：

近年来,越来越多的流行病学研究显示多种癌症与阿尔茨海默症（AD）呈现负相关,但分子生物学机制尚不明确。从基因信号传导及调控网络构建方面研究这种负相关,将对两种疾病致病机理的探寻起重要作用。选取乳腺癌（BC）与AD进行对比研究。考虑到传统特征基因提取方法注重单个基因在不同样本中的表达差异而忽视基因之间的关联性,从基因之间的关联性出发,利用互信息（MI）首先提取两种疾病中共有的差异表达基因作为特征基因。在此基础上,鉴于网络成分分析（NCA）约束条件较强、运行时间过长等局限性,采用快速网络成分分析算法（Fast NCA）,推演出特征基因中转录因子的表达活性及其对靶基因的调控强度,并分别构建两种疾病的转录调控网络。实验结果表明,转录因子POLR2E、RFC5、THOC4、FBXO22、KPNA1、MYST3、PTBP1等在两种疾病中表达活性及调控作用相反,如转录因子RFC5的表达活性从健康到BC患病过程中由0.269降低至0.077,而从健康到AD患病过程中则由-0.430升高至0.307。通过分子生物学分析可知,它们所影响的调控关系及生物过程对BC及AD的致病起着关键作用,对两种疾病之间呈现负相关性机制的探寻具有重要意义。

英文摘要：

In recent years,a growing number of epidemiological studies have shown that many kinds of cancer and Alzheimer＇s disease have an inverse association,but the molecular biological mechanism remains unclear.Researching the inverse association from gene signal transduction and regulatory networks will play an important role in exploring the pathogenesis of both diseases. Breast cancer（ BC） and AD were selected to be analyzed.Taking account of that the traditional genes extraction algorithms focused on a single gene expressed differently in different samples and ignored the links among the correlation genes,mutual information（ MI） was utilized to extract the differentially expressed genes in the two diseases basing on the correlation among genes using as feature genes. In this paper,considering the limitation of network component analysis（ NCA）,such as the strong constraint conditions and the long running time,fast-network component analysis（ Fast NCA）,improved by NCA,was brought up to get the activity of transcription factors among feature genes and TF＇ s regulate strength of target genes, and construct two diseases transcriptional regulatory networks, respectively.Experimental results showed that the activities and the regulate and control strength of TFs were totally oppositein the two diseases,for example POLR2 E,RFC5,THOC4,FBXO22,KPNA1,MYST3 and PTBP1,for example,transcription factors RFC5 activities in BC decreased from 0. 269 to 0. 077,and in AD increased by- 0. 430 to 0. 307. According to the experiment and analysis of molecular biology,the regulate relationship and the biological process influence from these TFs play a vital role in BC and AD.