基于特征序列和CGR方法对Rh血型基因特征的研究
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摘要
Rh血型系统作为人类最复杂的血型系统之一,其临床意义仅次于ABO血型系统。在临床输血实践中因ABO、Rh血型不合的妊娠或输血可发生输血反应和新生儿溶血病。本文的主要工作包括以下几个方面:
1、根据a, t, c, g的化学结构分类,给出了DNA序列的特征序列概念(σ-,τ-和στ-)并推广到蛋白质序列中,从而给出一种数值刻划,将蛋白质序列简化成一个(0,1)序列,并且应用到18条三种结构(α螺旋类,β折叠类,αβ类)的蛋白质序列中,得到了不同结构蛋白质序列的一些二级结构的信息。从另一种角度出发,根据氨基酸分子量与简并度的相关性,给出了DNA序列的特征序列概念(ω-)并推广到蛋白质序列中,通过数值刻划,将蛋白质序列简化成一个(0,1,2)序列,通过比较特征序列的数值刻划图,得出RHD基因和RHCE基因均偏爱使用低分子量且高简并度的氨基酸。
2、利用基于经典HP模型的蛋白质序列的混沌游走(Chaos game representation,简称CGR)的方法,给出了RHD基因的蛋白质序列的CGR图,可作为蛋白质序列的二级结构的一个特征图谱描述,同时给出了RHD基因的DNA序列的CGR图,并且计算出了RHD基因的相应的马尔可夫两步转移概率矩阵,从而得到RHD基因对编码氨基酸的三联子的第三个碱基的使用偏好性。
3、提出了一种新的氨基酸编码方法:拟氨基酸编码方法,并且计算了基于拟氨基酸编码方法下的78个人类基因的同义密码子的相对使用度,结果表明这些特征不但与石秀凡等人的研究结果一致,而且更为明显。说明了拟氨基酸编码方法更具合理性和科学性。进而计算了人类Rh血型系统中RHD基因基于拟氨基酸编码方法下的同义密码子相对使用度(QRSCU),以及QRFN3’,得出了RHD基因对密码子的偏好使用性以及后面所接碱基的偏好性。
本论文的创新点为:
1、提出了一种新的特征序列(ω-特征序列)。
2、利用提出的一种新的氨基酸编码方法:拟氨基酸编码方法,建立了QRSCU,并应用于Rh血型系统研究。
The Rh blood type system is one of the most complex of the known human blood type system, the clinical significant of which is only next to the ABO blood type system. It can cause transfusion reaction and hemolytic disease of the feyus and newborn(HDN) because of the pregnancy or blood transfusion of ABO,Rh blood type incompatibility in clinical practice of blood transfusion.
The main contents are listed as follows:
1. According to the chemical structure classification of a, t, c and g, these concepts ofσ-,τ- andστ-characteristic sequences have been presented and promoted into protein sequence, furthermore, the graph representation is introduced, and protein sequence is simplified to be (0,1) sequence, these characteristic sequences are applied to 18 protein sequences of three different kinds of structure(αhelix,βpucker,αβ), so we obtain some structural characteristic of protein sequences of different structure. From another point of view, according to the relation of the molecular weight and degeneracy of the amino acids, another concept of DNA characteristic sequences(ω-)is presented, and promoted into protein sequence, furthermore, through the graph representation, protein sequence is simplified to be (0,1,2) sequence, we can know that both RHD and RHCE genes all prefer to use the amino acids with small molecular weight and high degeneracy, by comparing the graph representation of the RHD and RHCE characteristic sequences.
2. This paper use the Chaos game representation (CGR) of protein sequences based on the detained HP model, it gives the CGR of the protein sequences of RHD gene, which can be regarded as characters map of the protein’s secondary structure of RHD gene. This paper still gives the CGR of the DNA sequences of RHD gene, it also compute the corresponding probability matrix for the second-order Markov Chain model. From the probability matrix, we can see the usage preference that the third base of the codons in the DNA sequence of the RHD gene.
3. This paper propose another genomic genetic codes: quasi-amino acids coding.The result of the relative usage degree of 78 human genes based on the quasi-amino acids coding indicates that these characteristic is not only consistent with the result of Shi Xiufan et al but more obvious, which show that the quasi-amino acids coding is more rational and scientific.It also compute the preference and the QRFN3’of synonymy codon based on quasi-amino acids coding of RHD gene,we obtain the preference to the synonymy codon of RHD gene and the preference to the base behind the synonymy codon.
The innovations are listed as follows:
1. Proposing a new kind of characteristic sequence(ω-).
2. Proposing a new kind of genomic genetic codes: quasi-amino acids coding, give out QRSCU and use it to research on the Rh blood type system.
1、根据a, t, c, g的化学结构分类,给出了DNA序列的特征序列概念(σ-,τ-和στ-)并推广到蛋白质序列中,从而给出一种数值刻划,将蛋白质序列简化成一个(0,1)序列,并且应用到18条三种结构(α螺旋类,β折叠类,αβ类)的蛋白质序列中,得到了不同结构蛋白质序列的一些二级结构的信息。从另一种角度出发,根据氨基酸分子量与简并度的相关性,给出了DNA序列的特征序列概念(ω-)并推广到蛋白质序列中,通过数值刻划,将蛋白质序列简化成一个(0,1,2)序列,通过比较特征序列的数值刻划图,得出RHD基因和RHCE基因均偏爱使用低分子量且高简并度的氨基酸。
2、利用基于经典HP模型的蛋白质序列的混沌游走(Chaos game representation,简称CGR)的方法,给出了RHD基因的蛋白质序列的CGR图,可作为蛋白质序列的二级结构的一个特征图谱描述,同时给出了RHD基因的DNA序列的CGR图,并且计算出了RHD基因的相应的马尔可夫两步转移概率矩阵,从而得到RHD基因对编码氨基酸的三联子的第三个碱基的使用偏好性。
3、提出了一种新的氨基酸编码方法:拟氨基酸编码方法,并且计算了基于拟氨基酸编码方法下的78个人类基因的同义密码子的相对使用度,结果表明这些特征不但与石秀凡等人的研究结果一致,而且更为明显。说明了拟氨基酸编码方法更具合理性和科学性。进而计算了人类Rh血型系统中RHD基因基于拟氨基酸编码方法下的同义密码子相对使用度(QRSCU),以及QRFN3’,得出了RHD基因对密码子的偏好使用性以及后面所接碱基的偏好性。
本论文的创新点为:
1、提出了一种新的特征序列(ω-特征序列)。
2、利用提出的一种新的氨基酸编码方法:拟氨基酸编码方法,建立了QRSCU,并应用于Rh血型系统研究。
The Rh blood type system is one of the most complex of the known human blood type system, the clinical significant of which is only next to the ABO blood type system. It can cause transfusion reaction and hemolytic disease of the feyus and newborn(HDN) because of the pregnancy or blood transfusion of ABO,Rh blood type incompatibility in clinical practice of blood transfusion.
The main contents are listed as follows:
1. According to the chemical structure classification of a, t, c and g, these concepts ofσ-,τ- andστ-characteristic sequences have been presented and promoted into protein sequence, furthermore, the graph representation is introduced, and protein sequence is simplified to be (0,1) sequence, these characteristic sequences are applied to 18 protein sequences of three different kinds of structure(αhelix,βpucker,αβ), so we obtain some structural characteristic of protein sequences of different structure. From another point of view, according to the relation of the molecular weight and degeneracy of the amino acids, another concept of DNA characteristic sequences(ω-)is presented, and promoted into protein sequence, furthermore, through the graph representation, protein sequence is simplified to be (0,1,2) sequence, we can know that both RHD and RHCE genes all prefer to use the amino acids with small molecular weight and high degeneracy, by comparing the graph representation of the RHD and RHCE characteristic sequences.
2. This paper use the Chaos game representation (CGR) of protein sequences based on the detained HP model, it gives the CGR of the protein sequences of RHD gene, which can be regarded as characters map of the protein’s secondary structure of RHD gene. This paper still gives the CGR of the DNA sequences of RHD gene, it also compute the corresponding probability matrix for the second-order Markov Chain model. From the probability matrix, we can see the usage preference that the third base of the codons in the DNA sequence of the RHD gene.
3. This paper propose another genomic genetic codes: quasi-amino acids coding.The result of the relative usage degree of 78 human genes based on the quasi-amino acids coding indicates that these characteristic is not only consistent with the result of Shi Xiufan et al but more obvious, which show that the quasi-amino acids coding is more rational and scientific.It also compute the preference and the QRFN3’of synonymy codon based on quasi-amino acids coding of RHD gene,we obtain the preference to the synonymy codon of RHD gene and the preference to the base behind the synonymy codon.
The innovations are listed as follows:
1. Proposing a new kind of characteristic sequence(ω-).
2. Proposing a new kind of genomic genetic codes: quasi-amino acids coding, give out QRSCU and use it to research on the Rh blood type system.
引文
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[2]赵国屏.生物信息学[M].北京:科学出版社,2002.
[3]孙向东,刘拥军.蛋白质结构预测[M].北京:科学出版社,2008.
[4]Trifonov E N.Earliest pages of bioinformatics[M].Bioinformatics,2000,16(1):5-9.
[5]Backofen R,Gilbert D.Bioinfoematics and constraints.Constraints,2001,6:141-156.
[6]钟杨,张亮,赵琼.简明生物信息学[M].北京:高等教育出版社,2001.
[7]郝柏林.生物信息学[J].中国科学院院刊,2000,(4):260—264.
[8]凃俐兰.基于快速沃尔什变换的生物序列相似性比对[D]:[硕士学位论文].武汉:华中科技大学计算数学,2004.
[9]许忠能.生物信息学[M].北京:清华大学出版社,2008.
[10]蒋彦,王小行,曹毅等.基础生物信息学及应用[M].北京:清华出版社,2003.1—16,102—186.
[11]蔡禄编著.生物信息学教程[M].北京:化学工业出版社,2006.1—62.
[12]塞图宝,梅丹尼斯.计算分子生物学导论[M].朱浩等译.北京:科学出版社,2003.1—20.
[13]李红.中心法则图解[EB/OL]. http://ebio.wjszzx.cn/html/2006-08/3446p15.htm, 2006—08—18
[14]Dan E.Krane & Michael L.Raymer生物信息学概论[M].北京:清华大学出版社.
[15]贺平安.DNA序列及蛋白质序列的分析与比较[D]:[博士学位论文].大连:大连理工大学,2004.
[16]黄延超.生物序列的非线性关联研究[D]:[博士学位论文].武汉:华中科技大学生物医学工程,2003.
[17]乔纳森·佩夫斯纳.生物信息学与功能基因组学[M].化学工业出版社.
[18].邹望远,郭曲练.Rh血型与输血的研究进展[J].国外医学输血及血液学分册2004.
[19].邵超鹏.RHD研究进展和中国人RHD研究现状分析[J].中国输血杂志2003.
[20].Westhoff CM. Rh血型系统:下一个十年的新面貌[J].国外医学输血及血液学分册2005,28(3):270-273.
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