以路徑表現量分析判定疾病反應路徑

Abstract

解開神秘的生命現象是科學家最大的夢想，長壽健康抗衰老更是普羅大眾的願望。人類從出生開始，便不斷的被各種疾病侵擾，其中有些疾病歸咎於基因的缺陷(如癌症)，罹病的人們往往只能等待死亡的降臨，無法有效的根治病灶；自2003年人類基因體(genome)完成定序，生物晶片(microarray)的技術發展日益成熟，疾病研究員不必像過往在實驗室中與基因博鬥，藉著科技的進步能細微且大量的分析人體基因表現量的變化，進而找出可能的關連性，使研究人員能針對特定基因進行臨床實驗，減少時間與金錢的浪費。近年來基因與疾病關係的研究往往是個別基因的分析，忽略了人體內調控機制的影響，隨著基因調控路徑的陸續發現，研究方向也漸漸朝向此一方向。然而，現有的基因路徑研究仍專注在少數基因身上，這樣的分析存在一個基本上的缺陷，所以我們思考一套新的研究方法，從建立全基因的調控網路(regulatory network)、尋找最短的調控路徑，各平台基因表現量的正規化(normalization)，分析疾病與調控路徑的關連性，最後驗證本方法之可信程度。在此，我們從公開的基因晶片資料庫GEO得到癌轉移(Metastasis)與子宮內膜異位症(Endometriosis)相關研究數據，找出可能促使癌轉移的基因，除可供給生技製藥的標靶藥物(drug target)開發，甚至可以將疾病反應路徑導向正常，進一步去阻斷癌症的轉移，降低癌症的死亡率，減少不必要之醫療資源之浪費。

To disclose the mysterious phenomenon of life is the biggest scientist’s dream, while living long, healthy and anti-aging is everyone’s desire. From the birth, humans are constantly infested with a variety of disease, some of them imputed to genetic defects (for example cancer). Unfortunately, diseased people only can tend to wait for death to come, without effectively care for the lesion. Since 2003, as sequence the Human genome, completed, it gets more sophisticated development for microarray technology. Disease researchers do not have to wrestle with the gene in the laboratory as in the past, by the progress of science and technology, making subtle, amounts of analysis of human gene express changes possible, and figure out the potential correlations, which allows them to conduct clinical trials and experiments for a particular gene. It will definitely reduce the waste of time and money. In recent years, the studies of relations of certainly focus on the analysis of individual gene, by ignoring the impact of the regulatory mechanism in the human body. As the gene regulatory pathways have been discovered, research has gradually toward the development of this direction. However, the existing genetic path still focus on a few specific genes, such analysis has a fundamental defect that we think about a new set of research method. It could find the shortest path from the whole established gene regulatory network, contract normalization of each platform, gene express, and to analyze the relevance of the disease, and the controlling path. Finally, the credibility of this method would be verified. At the point, we had been golem from the public gene database of relevant research data for Metastasis and Endometriosis to identify. In addition, it supplies biotechnology pharmaceutical to develop drug target, which disease reaction path can even be oriented to go farther blocking the transfer of cancer, with reducing cancer mortality and the unnecessary waste of medical resources.