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Title: 跨生物路徑資料庫探勘反饋迴路和耦合反饋迴路
Discovering feedback and coupled feedback loops from integrated pathway databases
Authors: Chen-Lung Liu
Contributors: NTOU:Department of Computer Science and Engineering
Keywords: 基因調控網路;生物路徑;反饋迴路;耦合反饋迴路
feedback loop;coupled feedback loop;biological pathway;gene regulatory network;orthologous;paralogous
Date: 2013
Issue Date: 2013-10-07T02:59:26Z
Abstract: 基因調控網路是由生物分子之間交互作用所形成,透過一群DNA分子直接或間接方式調控彼此以維持基因正常的表現。而基因調控網路中存在一種具有回授特性的調控機制稱之為反饋迴路,反饋迴路有正向及負向調控行為之分,該調控機制除控制基因表現量之餘亦連帶影響子網路的整體運作。許多實驗證實反饋迴路的重要性並發現反饋迴路經常以成對方式存在於基因調控網路當中,並稱之為耦合反饋迴路。此等重要的調控機制影響基因調控網路的運作及動態平衡。研究基因調控網路有助於打開人類或自然界生物於生長、疾病、死亡的關鍵鑰匙。但在現有的生物路徑資料庫中卻無法直接且明顯地發現反饋迴路存在。在本研究中,我們整合KEGG和Reactome兩大知名生物資料庫收錄的所有生物路徑圖,總數量超過1,500張生物路徑圖,透過自動解析處理不同資料庫的生物路徑,我們可以自動分析在生物路徑中所有基因上、下游的調控關聯性,整合並建構跨資料庫及跨生物路徑圖的反饋迴路和耦合反饋迴路機制。同時,我們還提出一項全新預測耦合反饋迴路的概念,結合物種同源基因資訊,探討已知反饋迴路是否存在相異的同源基因,透過已知反饋迴路與同源基因的結合,有機會發展成耦合反饋迴路。經由跨資料庫生物路徑整合以及反饋迴路探勘,有助於生物學家更方便進行生物路徑的進階研究。
Each gene regulatory network (GRN) involves a set of DNA components interacting with each other indirectly to control gene expression rates. Several sub-networks appear in a GRN holding feedback loop or coupled feedback loop mechanisms, which possess returning control mechanisms and aim to intervene or enhance certain functional conditions. Many cases have been reported and experimentally verified the existence of feedback loop relationships in transcription regulatory networks. However, most feedback loops were neither directly shown nor easy to be recognized from public pathway databases. In this study, we integrated two well-known pathway databases of KEGG and Reactome by parsing biological pathway maps into a common standard format, and the developed system could identify hidden feedback and coupled feedback loop information automatically through cross-database and cross-map analyses. We integrated and verified all possible cross-regulatory pathways from these two databases by examining each gene appeared in all collected pathway maps. Over 1,500 biological pathway maps were parsed and analyzed throughly, and an on-line web based system was designed for biologists to query any specified gene for its possible feedback relationships. In addition, paralogous gene information was considered for discovering potential coupled feedback loop relationships among various pathway maps. The built cross-linked pathways could facilitate biologists in understanding how the unveiled dynamic patterns of gene regulation maintain the balance of a specific biological function.
URI: http://ethesys.lib.ntou.edu.tw/cdrfb3/record/#G0010057049
Appears in Collections:[資訊工程學系] 博碩士論文

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