Public HIV Drug Resistance Database

描述（由申请人提供）：艾滋病毒耐药性数据对于艾滋病毒耐药性监测、抗逆转录病毒药物设计和耐药艾滋病毒感染者的管理至关重要。三种基本类型的相关性构成了耐药性知识的基础：(1)基因型数据与已获得HIV-1分离株测序的人的治疗之间的相关性（基因型-治疗）；(2)基因型与体外药敏的相关性（基因型-表型）；(3)基因型与新治疗方案临床反应的相关性（基因型-结局）。因此，我们的三个计划如下：(1)利用基于系统发育的统计分析，分析艾滋病毒治疗靶点（基因型）突变与抗逆转录病毒治疗之间的相关性，以区分与药物和非药物相关的艾滋病毒-1进化，确定耐药性流行的时间和地理模式，并确定具有特定耐药性突变模式的病毒的传播。(2)利用抗逆转录病毒治疗靶点的突变模式、抗逆转录病毒治疗数据和体外药敏结果，帮助优先考虑实验性抗逆转录病毒化合物的临床开发。(3)研究基因型-表型与基因型-临床结果之间的相关性，以确定对获得性或传播性耐药患者最有效的治疗方案。为了实现这些目标，我们将扩展在线公开可用的斯坦福HIV RT和蛋白酶序列数据库，以表示、存储和分析潜在耐药性知识的各种形式的数据。与研究HIV-1耐药性的广大研究人员交换数据的标准化协议将得到完善和验证。将实施表示已发表的耐药数据、执行时间查询和知识发现以及在系统发育背景下分析基因型耐药数据的改进方法。该提案也是斯坦福大学、伦敦大学学院和牛津大学三方合作的开始。伦敦大学学院在研究传播耐药性问题方面走在前列，牛津大学在研究病毒进化和群体遗传学方面走在前列。

DESCRIPTION (provided by applicant): HIV drug resistance data are critical for HIV drug resistance surveillance, antiretroviral drug design, and the management of persons infected with drug-resistant HIV. Three fundamental types of correlations form the basis of drug resistance knowledge: (1) Correlations between genotypic data with the treatments of persons from whom sequenced HIV-1 isolates have been obtained (genotype-treatment); (2) Correlations between genotype and in vitro drug susceptibility (genotype-phenotype); and (3) Correlations between genotype and the clinical response to a new treatment regimen (genotype-outcome). Accordingly our three plans are as follows: (1) To use phylogenetically-based statistical analysis of correlations between mutations in the targets of HIV therapy (genotype) and antiretroviral treatment to distinguish between drug- and non-drug- related HIV-1 evolution, to identify temporal and geographic patterns in the prevalence of drug resistance, and to identify the spread of viruses with particular patterns of drug-resistance mutations. (2) To use patterns of mutations in the targets of antiretroviral therapy, antiretroviral treatment data, and in vitro drug susceptibility results to help prioritize the clinical development of experimental antiretroviral compounds. (3) To us correlations between genotype-phenotype and genotype-clinical outcome to identify the treatment regimens most likely to be effective in persons with acquired or transmitted drug resistance. In order to accomplish these aims, we will expand the online publicly available Stanford HIV RT and Protease Sequence Database to represent, store, and analyze the diverse forms of data underlying drug resistance knowledge. Standardized protocols for exchanging data with the broad community of researchers studying HIV-1 drug resistance will be refined and validated. Improved methods for representing published drug resistance data, performing temporal queries and knowledge discovery, and for analyzing genotypic resistance data in a phylogenetic context will be implemented. This proposal is also the start of a three-way collaboration between Stanford University, the University College of London (UCL), and Oxford University. UCL is on the forefront of research into the problem of transmitted drug resistance and Oxford University is on the forefront of research on virus evolution and population genetics.