發展一改良之循環二元分割法應用於比較基因體雜合資料分析

Development of an Improved Segmentation Method Based on Circular Binary Segmentation for Array Comparative Genomic Hybridization

許方瀚(Fang-Han Hsu)

指導教授 ： 莊曜宇

共同指導教授 ： 陳ㄧ東

國立臺灣大學/電機資訊學院/電機工程學研究所/碩士(2007年)

https://doi.org/10.6342/NTU.2007.02671

摘要

去氧核醣核酸拷貝數(DNA copy number)的改變是染色體變異中的一種，此種變異與許多疾病有密切的相關，例如癌症。比較基因體雜合(aCGH)是偵測DNA拷貝數改變之一項新穎技術。經實驗獲得比較基因體雜合資料後，分割(Segmentation)往往是資料分析中的起始步驟。循環二元分割法(DNAcopy)是一常見之分割演算法；因擁有良好靈敏度及斷點錯誤發現率之特性，所以被生物學者們所廣為使用。然而，由於其龐大之電腦計算需求，使得此法在分析大型資料組時，有速度上的侷限。本研究提出一改良之循環二元分割法，稱為高速循環二元分割法(Faster Circular Binary Segmentation)。此法引用了Student’s t-distribution估算t檢定中的 p-value值，並導入delayed decision作進一步地速度改良。同時，運用模擬資料證實高速循環二元分割法在準確度上之極小損失。最後，本研究實際分析了兩筆比較基因體雜合實驗資料，用以針對循環二元分割與高速循環二元分割兩種演算法，作時間效能與演算法速度之深入比較。

關鍵字

比較基因體雜合 ； 去氧核醣核酸拷貝數 ； 分割法 ； 循環二元分割法 ； 高速循環二元分割法

並列摘要

Chromosomal aberration in the form of DNA copy number changes correlates with numerous disease including cancer. aCGH is a novel technique to detect the DNA copy number changes. For a given genomic profile, the initial computational process in aCGH data analysis is commonly referred to as “segmentation”. DNAcopy, one of the most popular segmentation methods, has good sensitivity and False Discovery Rate (FDR) for breakpoint detection. However, the time-consuming process of computation prohibits the method from analyzing large dataset. Based on DNAcopy, we proposed an improved segmentation method, called Faster Circular Binary Segmentation (FCBS). The approximation of the p-value of t-test by using Student’s t-distribution is applied to speed up the algorithm and a delayed decision is introduced for further improvement. We show through simulation that our method has minimal effect on accuracy. Finally, two aCGH datasets were analyzed and the time consumption of DNAcopy and FCBS was compared and studied.

並列關鍵字

aCGH ； DNA copy numbers ； segmentation ； DNAcopy ； FCBS

參考文獻

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