革新的疾病相關路徑鑑定法：以心肌梗塞跨平台資料為例

人類從出生開始便被不可預知的疾病所困擾著，人們試著用各種方法遠離疾病的糾纏，各式研究也隨之展開；從基因的角度來看疾病，以往生物學家在實驗室中與少數幾個基因搏鬥的血淚史已成為過去式，隨著科技的進步讓我們能以更大量且細微的探索人體基因體表現的變化。隨著各種研究漸趨成熟與支持，基因與疾病的研究由單獨基因的解析，推向基因調控以至於基因反應路徑的研究，人們相信基因相互的調控關係與疾病的產生有著密不可分的關連，因此近年來基因調控網路成為相當熱門的議題；現有的基因路徑分析法存在著許多根本性的問題，且在眾多的研究中獨缺整合全基因調控網路並以全路徑為觀點的分析，這樣的缺憾讓基因路徑分析無法跳脫傳統觀察少數基因的包袱，因此我們建立一套疾病相關路徑鑑定方法，除了不同於以往以基因表現量的方法分析，也打破了現有的反應路徑分析法；從建立全基因調控網路、最短反應路徑尋找、反應路徑與疾病關係的分析判定，到驗證分析方法的可信度。此方法目的在判別與疾病有關連性之反應路徑，相信必能精確指出與疾病相關的基因與基因調控路徑，除了開拓路徑分析的新視野外，更提供給生技製藥的標靶藥物開發更好的選擇。

關鍵字

基因調控網路；路徑分析

並列摘要

Since the day we were born, we have been afflicted with all kinds of illness and diseases. To reduce the pain and fear, all kinds of approaches to attack diseases have been developed. From the aspect of genetics studies, the researchers used to work on a couple of genes that might relate to diseases in all their scientific life. However, along with the advance of biotechnology, we are able to trace and monitor the alteration of gene expression in a whole-genome scale. Furthermore, the chances are the approaches have been moved from individual gene studies to gene-gene interactions and even the gene network, as it is believed that genes are collaboratively functioning in groups instead of working by themselves alone. Therefore, pathway analysis has been getting more attention recently. However, the pathway analysis used update exists many unsolved issues, most importantly, it lacks the integrity of whole-genome regulated networks that actually reflect the gene reaction pathways. We develop a method to identify “Disease-associated Pathways”. Here in this study, we will (1) develop a regulatory gene network by combining each gene-gene reaction pair, (2) identify the shortest pathways from a whole genome network, (3) establish pathway analysis algorithms to calculate the full pathway expression value, and (4) distinguish the disease and non-disease pathways by incorporating microarray data. The purpose of this pipe-line approach is to quest for disease-associated pathways and by unveiling the pathways, it will also provide a better choice for drug target in pharmaceutical industry in the near future.

並列關鍵字

Gene Network ； Pathway Analysis

參考文獻

1.(2006) The Gene Ontology (GO) project in 2006. Nucleic Acids Res 34: D322-326

2.(2008) The Gene Ontology project in 2008. Nucleic Acids Res 36: D440-444

3.Alvo M, Liu Z, Williams A, Yauk C (2010) Testing for mean and correlation changes in microarray experiments: an application for pathway analysis. BMC Bioinformatics 11: 60

4.Chen L, Xuan J, Gu J, Wang Y, Zhang Z, Wang TL, Shih leM (2012) Integrative network analysis to identify aberrant pathway networks in ovarian cancer. Pac Symp Biocomput 2012:31-42

5.Fang Z, Tian W, Ji H, (2011) A network-based gene-weighting approach for pathway analysis. Cell Res. 2011 Sep 6. doi:10.1038/cr.2011.149.

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革新的疾病相關路徑鑑定法：以心肌梗塞跨平台資料為例

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