以留一單因子穩健多變量變異數分析來篩選阿茲海默症的致病基因

阿茲海默症是一種神經退化性疾病，俗稱老年癡呆，以現今醫學來說為不可逆的疾病，無論是對家庭和社會都耗費許多資源。在病理上，阿茲海默症的病因與大腦中的纖維狀類澱粉蛋白質斑塊沉積和Tau蛋白有關，這些物質由部分基因轉譯而成，本文的目的即是尋找出致病基因。使用的方法是基於傳統「變異數分析」(ANOVA) 的改良，推出「留一單因子穩健多變量變異數分析」(leave-one-out one-way robustify MANOVA)，與傳統變異數分析相比，此方法不須任何前提假設，且表現結果勝過傳統的變異數分析、雙樣本t檢定 (two sample t test) 、微陣列資料線性模型(Linear Models for Microarray Data，簡稱limma) 與微陣列顯著性分析 (Significance analysis of microarrays，簡稱SAM)。每種方法所篩選出來的基因都用現有文獻驗證，另外還做模擬以檢驗此方法的正確性。本文使用的基因微陣列資料(microarray expression)來自歐洲分子生物學實驗室 (EMBL)，以此來分析十三位正常人與二十二位阿茲海默症病患的基因差異。

關鍵字

變異數分析；阿茲海默症；微陣列晶片；基因；神經退化性疾病

並列摘要

Alzheimer's disease is a neurodegenerative disease which commonly known as senile dementia. It is an irreversible disease in today's medical treatment, and it consumes a lot of resources for both the family and society. Pathologically, the cause of Alzheimer's disease is related to the deposition of fibrous amyloid plaques and Tau protein, which are translated from genes, in the brain. The purpose of this thesis is to find the pathogenic genes for Alzheimer’s disease. The method is based on the improvement of the traditional "Analysis of variance" (ANOVA), which is "leave-one-out one-way robustify MANOVA". Compared with the traditional analysis of variance, this method does not require any assumptions, and the performance of this method outperform the traditional analysis of variance, two sample t test, Linear Models for Microarray Data (limma) and Significance analysis of microarrays (SAM). The genes selected by each method were verified by existing literature. The simulations were conducted to show the advantage of the method. The microarray expression used in this thesis is publicly available from the European Molecular Biology Laboratory (EMBL). Here we use the microarray data to analyze the genetic differences between thirteen normal people and twenty-two Alzheimer's patients.

並列關鍵字

Analysis of variance ； Alzheimer's disease ； microarray expression ； gene ； neurodegenerative disease

參考文獻

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以留一單因子穩健多變量變異數分析來篩選阿茲海默症的致病基因

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