权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

INFERENCE OF EVOLUTIONARY CHANGES OF WITHIN-HOST VIRUS

宿主内病毒进化变化的推论

基本信息

批准号：
15510157
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We have previously proposed an algorithm, distance-based sequential-linking method, for longitudinal analysis of within-host viral evolution and successfully reconstructed a longitudinal phylogenetic tree of 24 HIV-1 env gene sequences obtained from patients who had not received drug treatment. However, viral evolution in patients who are undergoing drug therapy, especially HARRT (Highly Active Anti-Retroviral Therapy), is much more complicated because of the selective pressure from the anti-viral drugs. To estimate this complicated process, we largely improved the previous algorithm by introducing information criterion into our method. We employed C4.5 (software package, Quinlan, 1993), which is developed based on mutual information criterion, to obtain the decision tree that identifies the relations between virus samples and drug combinations administered. We applied the revised algorithm to a large data set (189 sequences) of HIV-1 protease gene serially sampled from a single patient under HAART over three years. The obtained decision tree showed that there were always two or more viral subpopulations with different frequencies and also different characteristic mutations during the whole observation period. Moreover, by estimating the synonymous (ds) and nonsynonymous (d_N) substitution rates of each viral subpopulation classified by the decision tree, we found that the selective pressure exerted on the virus is highly variable over time when different drugs are administered, but the virus may often be under positive Darwinian selection to evolve.The above results have been presented at several meetings including international meetings (SMBE2004, ISMB2004), and received the "Excellent Theme Prize" from the 18th annual meeting of the Japanese society for AIDS research

我们以前提出了一种算法，基于距离的序列连接方法，用于纵向分析宿主内病毒进化，并成功地重建了24个HIV-1 env基因序列的纵向系统发育树，这些序列来自未接受药物治疗的患者。然而，由于抗病毒药物的选择性压力，正在接受药物治疗，特别是HARRT（高活性抗逆转录病毒治疗）的患者中的病毒演变要复杂得多。为了估计这个复杂的过程，我们对以前的算法进行了很大的改进，引入了信息准则。我们使用基于互信息准则开发的C4.5（软件包，Quinlan，1993）来获得识别病毒样本与给药药物组合之间关系的决策树。我们应用修改后的算法，一个大的数据集（189序列）的HIV-1蛋白酶基因连续采样从一个单一的病人下HAART超过三年。决策树分析表明，在整个观察期内，总有两个或两个以上的病毒亚群存在不同的频率和不同的特征突变。此外，通过估计由决策树分类的每个病毒亚群的同义（ds）和非同义（d_N）替换率，我们发现当施用不同药物时，施加在病毒上的选择压力随时间变化很大，但病毒可能经常在达尔文的积极选择下进化。上述结果已在包括国际会议在内的几次会议上提出（SMBE 2004，ISMB 2004），并获得日本艾滋病研究学会第18届年会的“优秀主题奖”