以生物資訊方法建立疾病調控網路-阿茲海默症為例

In Silico Disease Regulatory Pathway construction – Alzheimer’s Disease

廖晃聖(Liao Huang-Sheng)

指導教授 ： 吳家樂

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2008年)

摘要

阿茲海默症(Alzheimer’s disease, AD)，它是因為神經退化，而導致人類記憶和某些生活上本能逐漸的喪失。本研究論文以阿茲海默症為例，目的在篩選出與阿茲海默症相關的轉錄因子，並預測其蛋白質與蛋白質相互作用網路及基因調控網路。
本研究中應用了NCBI資料庫，收集與AD相關的蛋白質。另一方面則利用了數個蛋白質資料庫收集人類轉錄因子之資料。與AD相關的轉錄因子資料篩選，則是透過關鍵字如neuron、cereblllum或brain在HPRD、Gene Ontology 和NCBI GEO資料庫去篩選出它們的組織表達位置和molecular function。
由於轉錄因子的突變常導致與之作用的蛋白質或其調控的下游基因發生改變，形成疾病。 本研究共找到五個可能與AD相關的轉錄因子及十個與AD相關的蛋白質，其中的四個在現有文獻中已有記載。此外共預測出17個被AD轉錄因子調控的下游基因。這一個轉錄因子相互作用網路及其調控的基因網路，可作為研究AD的模型。
另外也加入ArrayExpress進行分析，使用ArrayExpress的Microarray資料與文獻進行比對，經過比對後，分別得出與文獻AD相關的蛋白質1筆，而與文獻AD相關轉錄因子比對，分別得出與transcription factor activity function相關的為5筆 、DNA binding function為6筆，這些比對出來的資料在microarray裡都是屬於高表現量的。本研究成果網頁的網址如下: http://210.70.82.82/ADwebsite/。

關鍵字

阿茲海默症 ； 神經退化 ； 茲海默症 ； 表現量 ； 關鍵字 ； 資料庫 ； 蛋白質 ； 轉錄因子 ； 基因表現 ； 蛋白質與蛋白質相互作用 作用 蛋白質與蛋白質相互 作用 ； 疾病調控路徑

並列摘要

Alzheimer’s disease (AD) is a progressive neurodegneerative disease, causing the human memory and certain instinct loss gradually. The goal of this thesis is to identify AD-related transcription factors (TFs), construct the transcription factors’ protein-protein interaction network and gene regulation network.
This research employed the NCBI dataset to collect AD-related proteins, and made use of several protein datasets to screen out the AD-related TFs. These AD-related TFs are subjected to further queries, such as using the HPRD, the Gene Ontology and the NCBI GEO databases to filter out the tissue expression sites (such as neuron, cereblllum and brain), biological functions and the gene expression profile information respectively.
If a TF get mutated or defected, it could have profound effects on the downstream genes in the gene regulation pathway, and causing diseases. This work identified five AD-related TFs and ten AD-related proteins. Among these 15 proteins four are recorded in the existing literature. In addition 17 genes are predicted to be regulated by three of the 15 TFs. This putative transcription factor protein-protein interaction network and the gene regulation network could possibly used as a molecular map for AD study.
Furthermore, we made use of the ArrayExpress microarray data to identify AD-related TFs. We found one AD-related proteins and 11 TFs, in which five perform transcription factor activity function and the rest 6 perform the DNA binding function. All results are available at http://210.70.82.82/ADwebsite/index.php.

並列關鍵字

Alzheimer’s disease (AD) ； nerve degenerates ； transcription factor ； gene expression ； protein-protein interaction ； diseaseregulatory pathway interaction

參考文獻

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