A New Algorithm for Analysis of Within-host Viral Evolution

一种分析宿主内病毒进化的新算法

• 批准号: 13680758
• 负责人: REN Fengrong
• 金额: $ 1.6万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680758/
• 关键词: Within-host viral evolution; Neutral evolution; Positive selection; Codon-based model; Sequential-linking algorithm; Serial viral samples; Longitudinal phylogenetic reconstruction; Sequential-linkingアルゴリズム

The purpose of this study is to develop a computational method that would be simple and easy to use for the analysis of within-host viral evolution. Our method has two important features: noncontemporaneous viral samples can be dealt with by a simple computing algorithm, and both neutral and adaptive evolution patterns occurring during the process of viral evolution can be estimated. In the beginning stage of this research, we proposed a preliminary formulation of this algorithm that was based on the maximum likelihood method. However, it was difficult to use because the calculation of the likelihood required an extremely large amount of time and the number of possible tree topologies increased exponentially according to the increase in the number of viral variants. Therefore, we proposed another new algorithm, referred to as a distance-based sequential-linking algorithm, in which the neighbor-joining method is employed. This algorithm is applied to a longitudinal data set of the env gene (V3 region) of HIV-1 obtained over seven years after the infection of a single patient. The results suggest that this method can successfully reconstruct a longitudinal phylogenetic tree from noncontemporaneous viral samples within a reasonable calculation time.Further development of this method would include an incorporation of the merits of the sUPGMA, which would allow for an estimation of the Ne and the internal sample times ; we would also like to use densely serial samples of HIV-1 with this method for further verification of its efficiency. Collaborative research with the NIID (National Institute of Infectious Diseases) of Japan applying our method to a large data set of the pol gene of HIV-1 is in progress.

本研究的目的是开发一种简单易行的计算方法，用于分析宿主内病毒进化。我们的方法有两个重要的特点：非同期的病毒样本可以处理一个简单的计算算法，和中性和适应性的进化模式发生在病毒进化过程中，可以估计。在本研究的开始阶段，我们提出了一个初步的配方，这个算法是基于最大似然法。然而，它很难使用，因为计算可能性需要非常大量的时间，并且可能的树拓扑的数量根据病毒变体数量的增加而呈指数级增加。因此，我们提出了另一种新的算法，称为基于距离的顺序连接算法，其中采用的邻居连接方法。该算法被应用到一个纵向的数据集的env基因（V3区）的HIV-1感染后的一个单一的病人超过7年。结果表明，该方法可以在合理的计算时间内成功地从不同时期的病毒样本中构建纵向系统发育树，进一步发展该方法将包括结合sUPGMA的优点，这将允许估计Ne和内部采样时间;我们还想用这种方法使用密集的HIV-1系列样品，以进一步验证其效率。与日本NIID（国立传染病研究所）的合作研究正在进行中，将我们的方法应用于HIV-1的pol基因的大数据集。

项目成果

Fengrong Ren (任鳳蓉): "A New Algorithm for Analysis of Within-host HIV-1 Evolution"Biocomputing PubMed Identifier : 11262976. PSB(6). 595-605 (2001)

任凤荣：“一种分析宿主内 HIV-1 进化的新算法”生物计算 PubMed 标识符：11262976。PSB(6) 595-605 (2001)。

Fengrong Ren: "Longitudinal phylogenetic tree of within-host viral evolution from noncontemporaneous samples : a distance-based sequential-linking method"GENE. in press. (2003)

任凤荣：“来自非同期样本的宿主内病毒进化的纵向系统发育树：基于距离的顺序链接方法”GENE。

Fengrong Ren: "Inference and Prediction of Courses Courses of the Diseases Caused by Pathologic Viruses by Estimating Molecular Evolution of Within-host Virus"MEDINFO Pub Med Identifier : in preparation. 10(11). 979-983 (2001)

任凤荣：“通过估计宿主内病毒的分子进化来推断和预测病理病毒引起的疾病的病程”MEDINFO Pub Med Identifier：正在准备中。

Fengrong Ren: "A New Algorithm for Analysis of Within-host HlV-1 Evolution"Biocomputing PubMed Identifier. 11262976. PSB(6). 596-605 (2001)

任凤荣：“一种分析宿主内 HIV-1 进化的新算法”生物计算 PubMed 标识符。

Soichi Ogishima: "Reconstruction and Anaysis of Within-host Longitudinal HIV-1 Evolution by a Distance-based Sequential-linking Algorithm"Chem-Bio Informatics Journal. 1(2). 73-83 (2001)

Soichi Ogishima：“通过基于距离的序列链接算法重建和分析宿主内纵向 HIV-1 进化”《化学-生物信息学杂志》。