隨機選取DNA序列包含TFO之機率

On the Probability of Observing a Triplex Forming Oligonucleotide in a Randomly Selected DNA Sequence

薛凱薰(Kai-hsun Hsueh)

指導教授 ： 許文郁

國立清華大學/理學院/統計學研究所/碩士(2006年)

https://doi.org/10.6843/NTHU.2006.00056

摘要

Triplex Forming Oligonucleotide (TFO) is extensively used in gene therapy in recent years. It is a short segment of at least thirteen consecutive purines (A or G) or at least thirteen consecutive pyrimidines (C or T) in a DNA sequence. It is not easy to observe a TFO in a DNA sequence. Hence, determining the probability of finding a TFO in a given DNA sequence is the focus of many academics’ attentions. In past years, some methods evaluating this probability have been proposed. However, most of these methods lack of accuracy.
In this paper we propose a coin tossing model to describe the occurrence of a TFO in a randomly selected DNA sequence. The expectation and variance of the number of base pairs required to observe a TFO are calculated exactly. The coin tossing model possesses the nice property of approximate memoryless. Hence, the number of tosses needed until the appearance of some specific pattern has a distribution approximate to exponential one. Consequently, the probability of finding a TFO in a given sequence of DNA can be approximated by an exponential distribution. Some simulations are also made to confirm this result.

關鍵字

TFO ； 硬幣投擲模型 ； 指數近似

並列摘要

Triplex Forming Oligonucleotide (TFO) is extensively used in gene therapy in recent years. It is a short segment of at least thirteen consecutive purines (A or G) or at least thirteen consecutive pyrimidines (C or T) in a DNA sequence. It is not easy to observe a TFO in a DNA sequence. Hence, determining the probability of finding a TFO in a given DNA sequence is the focus of many academics’ attentions. In past years, some methods evaluating this probability have been proposed. However, most of these methods lack of accuracy.
In this paper we propose a coin tossing model to describe the occurrence of a TFO in a randomly selected DNA sequence. The expectation and variance of the number of base pairs required to observe a TFO are calculated exactly. The coin tossing model possesses the nice property of approximate memoryless. Hence, the number of tosses needed until the appearance of some specific pattern has a distribution approximate to exponential one. Consequently, the probability of finding a TFO in a given sequence of DNA can be approximated by an exponential distribution. Some simulations are also made to confirm this result.

並列關鍵字

Triplex Forming Oligonucleotides ； coin tossing model ； exponential approximation

參考文獻

Goñi, J.R., de la Cruz, X. and Orozco, M. (2004) Triplex-forming oligonucleotide target sequences in the human genome. Nucleic Acids Res., 32. 354-360

Guntaka, R.V., Varma, B.R. and Weber, K.T. (2003) Triplex-forming oligonucleotides as modulators of gene expression. Int J Biochem Cell Biol. 35. 22-33

Perkins, B.P., Wilson, J.H., Wensel, T.G. and Vasquez, K.M. (1998) Triplex Targets in the Human Rhodopsin Gene. Biochemistry. 37. 11315-11322

Ross, S.M. Introduction to probability models, eighth edition. U.S.A. Academic Press