本文選題：信號(hào)傳導(dǎo)通路預(yù)測(cè) + 信號(hào)通路相互作用網(wǎng)絡(luò)　； 參考：《華東師范大學(xué)》2012年碩士論文

【摘要】：人類信號(hào)傳導(dǎo)通路的研究歷來是探索生物過程機(jī)理的重要概念,是一種外界刺激信號(hào)交流傳遞的方式.信號(hào)通路幾乎滲透在的生物過程的各個(gè)部分,可以引起細(xì)胞的代謝、分裂、分化和凋亡.大量的實(shí)驗(yàn)研究已經(jīng)提出,信號(hào)通路的激活,抑制和改變與疾病的發(fā)生密切相關(guān),是引起癌癥的主要原因之一.這個(gè)機(jī)理的挖掘在癌癥藥物的開發(fā)中利用廣泛,可以設(shè)計(jì)靶向信號(hào)傳導(dǎo)通路的藥物,通過調(diào)節(jié)信號(hào)通路來影響靶基因的表達(dá)水平,從而起到抑癌的作用,這類研究在臨床上已初見成效.由此可見,研究信號(hào)傳導(dǎo)通路的機(jī)制和功能與人類生活的健康息息相關(guān),十分重要的. 但是,信號(hào)通路本身的特點(diǎn)又給研究帶來巨大的阻礙,通路在特定條件下的運(yùn)作機(jī)制還是未知的.信號(hào)通路的結(jié)構(gòu)是一個(gè)復(fù)雜的路徑網(wǎng)絡(luò),涉及在不同生理?xiàng)l件下的許多特異性生物開關(guān),起到活化或抑制功能通路的作用,同時(shí),不同的信號(hào)通路之間也并不是獨(dú)立運(yùn)作的,以多條通路相互協(xié)作來影響生物過程的這種模式是普遍存在的.因此在在繁雜的結(jié)構(gòu)體系中摸索其專一且富有規(guī)律的通路機(jī)制是研究的關(guān)鍵. 本文的目的是基于構(gòu)建一個(gè)成熟完善的分析流程,可以通過在人類芯片表達(dá)水平上的改變來預(yù)測(cè)具體哪一個(gè)上游信號(hào)通路進(jìn)行的信號(hào)刺激.在整合各個(gè)數(shù)據(jù)庫信號(hào)通路信息的基礎(chǔ)上,結(jié)合多種基因水平信息的關(guān)系網(wǎng)絡(luò),對(duì)不同信號(hào)通路中直接調(diào)控的”特征基因”(signature genes)進(jìn)行判定.然后,借鑒網(wǎng)絡(luò)權(quán)重通路分析的模型就不同信號(hào)通路下”特征基因”的特異性影響強(qiáng)度對(duì)通路計(jì)算富集檢驗(yàn)p值.本文另一特色是試圖構(gòu)建有節(jié)點(diǎn)差異的信號(hào)通路間相互作用(cross-talk)的網(wǎng)絡(luò).是一種基于多信息采集,網(wǎng)絡(luò)系統(tǒng)分析,權(quán)重重點(diǎn)關(guān)注計(jì)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.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R363

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本文編號(hào)：2023191