从基因差异表达回溯上游信号传导通路的富集分析

发布时间：2018-06-15 18:57

本文选题：信号传导通路预测 + 信号通路相互作用网络　；参考：《华东师范大学》2012年硕士论文

【摘要】：人类信号传导通路的研究历来是探索生物过程机理的重要概念,是一种外界刺激信号交流传递的方式.信号通路几乎渗透在的生物过程的各个部分,可以引起细胞的代谢、分裂、分化和凋亡.大量的实验研究已经提出,信号通路的激活,抑制和改变与疾病的发生密切相关,是引起癌症的主要原因之一.这个机理的挖掘在癌症药物的开发中利用广泛,可以设计靶向信号传导通路的药物,通过调节信号通路来影响靶基因的表达水平,从而起到抑癌的作用,这类研究在临床上已初见成效.由此可见,研究信号传导通路的机制和功能与人类生活的健康息息相关,十分重要的. 但是,信号通路本身的特点又给研究带来巨大的阻碍,通路在特定条件下的运作机制还是未知的.信号通路的结构是一个复杂的路径网络,涉及在不同生理条件下的许多特异性生物开关,起到活化或抑制功能通路的作用,同时,不同的信号通路之间也并不是独立运作的,以多条通路相互协作来影响生物过程的这种模式是普遍存在的.因此在在繁杂的结构体系中摸索其专一且富有规律的通路机制是研究的关键. 本文的目的是基于构建一个成熟完善的分析流程,可以通过在人类芯片表达水平上的改变来预测具体哪一个上游信号通路进行的信号刺激.在整合各个数据库信号通路信息的基础上,结合多种基因水平信息的关系网络,对不同信号通路中直接调控的”特征基因”(signature genes)进行判定.然后,借鉴网络权重通路分析的模型就不同信号通路下”特征基因”的特异性影响强度对通路计算富集检验p值.本文另一特色是试图构建有节点差异的信号通路间相互作用(cross-talk)的网络.是一种基于多信息采集,网络系统分析,权重重点关注计算的有效模型.
[Abstract]:The study of human signal transduction pathway has always been an important concept to explore the mechanism of biological process and a way to stimulate the communication and transmission of signals. Signaling pathways permeate almost every part of the biological process, causing cell metabolism, division, differentiation, and apoptosis. A large number of experimental studies have suggested that activation, inhibition and alteration of signaling pathways are closely related to the occurrence of disease, which is one of the main causes of cancer. This mechanism is widely used in the development of cancer drugs and can be used to design drugs targeting signal transduction pathways, which can affect the expression level of target genes by regulating the signal pathway, and thus play a role in cancer suppression. This kind of research has achieved initial clinical results. Therefore, it is very important to study the mechanism and function of signal transduction pathway, which is closely related to the health of human life. However, the characteristics of signaling pathway itself bring great obstacles to the study, and the operating mechanism of the pathway under certain conditions is still unknown. The structure of the signaling pathway is a complex network of pathways that involve many specific biological switches under different physiological conditions that activate or inhibit the functional pathways, and at the same time do not operate independently among the different signaling pathways. This pattern of multiple pathways working together to influence biological processes is common. Therefore, it is the key to explore its unique and regular pathway mechanism in the complicated structure system. The purpose of this paper is to construct a mature analytical process to predict which upstream signal pathway is stimulated by changes in the expression level of human chips. On the basis of integrating the information of signal pathways in various databases and combining the relationship networks of multiple gene level information, the "signature geneses", which are directly regulated by different signal pathways, are judged. Then, using the model of network weight path analysis, the specific influence intensity of "characteristic gene" on the path calculation enrichment test p value under different signal pathways is discussed. Another feature of this paper is that we try to construct a cross-talk network of signaling pathways with nodal differences. It is an effective model based on multi-information collection, network system analysis and weight calculation.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R363

【参考文献】