基于互信息研究的乳腺癌与阿尔茨海默症的免疫系统发病机理探寻

发布时间：2017-12-26 17:12

本文关键词：基于互信息研究的乳腺癌与阿尔茨海默症的免疫系统发病机理探寻　出处：《中国生物医学工程学报》2016年03期 　论文类型：期刊论文

【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。
[Abstract]:In recent years, more and more epidemiological studies have shown that multiple cancers have a negative correlation with Alzheimer's disease (AD), but the molecular biological mechanism is not yet clear. The study of this negative correlation from genetic signal transduction and regulatory network will play an important role in the exploration of the pathogenesis of the two diseases. Breast cancer (BC) was compared with AD. Considering the traditional feature extraction method of gene expression between individual genes in different samples and ignore the correlation between genes, starting from the relationship between genes, the use of mutual information (MI) extracted from two kinds of diseases are common differentially expressed genes as the characteristic gene. On this basis, in view of the network component analysis (NCA) constraint conditions of strong and long operation time limitations, using fast network component analysis algorithm (Fast NCA), the expression of transcription factor activity to deduce the feature genes and the intensity of regulation of target genes, transcriptional regulatory networks were constructed and two kinds of diseases. The experimental results show that the transcription factor POLR2E, RFC5, THOC4, FBXO22, KPNA1, MYST3 and PTBP1 in two kinds of disease activity and expression of opposite regulation, such as the expression of the transcription factor RFC5 from healthy to the prevalence of BC process decreased from 0.269 to 0.077, and from health to AD in the course of illness is increased from -0.430 to 0.307. Through molecular biological analysis, we can know that their regulatory relationships and biological processes play a key role in the pathogenesis of BC and AD. It is important to explore the mechanism of negative correlation between the two diseases.
【作者单位】：上海海事大学信息工程学院;美国罗文大学生物化学系;
【基金】：国家自然科学基金(61271466) 上海市教委科研创新项目(15ZZ079)
【分类号】：R737.9;R749.16
【正文快照】： 2(美国罗文大学生物化学系,美国新泽西08028)引言近年来,越来越多的流行病学统计显示癌症与老年痴呆症特别是阿尔茨海默症(Alzheimer'sdisease,AD)之间呈现负相关即癌症患者患AD的可能性较其他人大幅降低,反之亦然[1]。为了更清楚地了解癌症和AD之间负相关关系,很多学者就癌症

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