Enhancement of the HIV Antibody Database tool for Open Science

增强开放科学的 HIV 抗体数据库工具

• 批准号: 10406832
• 负责人: Pamela J Bjorkman
• 金额: $ 14万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-31 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406832
• 关键词: AIDS/HIV problem; Adopted; Adoption; Animal Model; Antibodies; Antigens; Binding; Bioinformatics; Computer software; Data; Data Analyses; Data Science; Data Set; Data Sources; Databases; Development; Ensure; Evaluation; Goals; Grant; HIV Antibodies; HIV-1; HIV-1 vaccine; Human; Knowledge; Macaca; Mutation; Output; Pattern; Performance; Phylogenetic Analysis; Public Health; Pythons; SARS-CoV-2 genome; Scheme; Secure; Software Tools; Source; Standardization; Structure; Testing; Transgenic Mice; Vaccine Design; Vaccines; Variant; Viral; Virus; analytical tool; base; data archive; data streams; design; experimental study; genomic epidemiology; improved; innovation; interoperability; neutralizing antibody; open data; open source; programs; reconstruction; screening; software development; tool; vaccine trial

Project Summary The goal of our P01 HIVRAD Project is to advance our germline-targeting approach to HIV-1 vaccine design by cycles of immunogen design and testing in transgenic mice and macaques. The experiments proposed in this P01 grant will produce candidate immunogens for testing in macaques by collaborator Dr. Malcolm Martin and for vaccine trials in humans. One innovative aspect of the project is its integrated approach to structure determination and immunogen design, selection, and evaluation - the same people solving structures are also involved with immunogen design and screening, allowing a rapid and informed cycle of iterative improvements of immunogens. As part of this integrated approach, the Bjorkman lab has developed the software package HIV Antibody Database, which was designed to enable frictionless access to, comparisons of, and analyses of broadly neutralizing anti-HIV antibody sequences, structures, and neutralization data. This program includes a data analysis tool to identify HIV-1 Env sequence features responsible for neutralization/binding potency variability across strains. This innovative tool has allowed us to determine key interactions at Ab/Env interfaces using a combination of structural and bioinformatics analyses. We propose to enhance the HIV Antibody Database tool by improving its robustness and sustainability by integrating publicly available data streams, adopting standard formats for input and output of structural data, optimizing performance, and integrating another program developed by the Bjorkman lab, Variant Database, which can query a viral mutational landscape. Variant Database can quickly search SARS-CoV-2 genome datasets with over a million sequences. Thus, it can be used to detect emerging mutation patterns that might be overlooked in conventional phylogenetic analyses. We propose to generalize Variant Database to analyze different virus taxa, including HIV-1. Variant Database will be enhanced to be more robust and sustainable, and this version will be integrated with HIV Antibody Database.

项目概要 我们的 P01 HIVRAD 项目的目标是推进我们针对 HIV-1 的种系靶向方法 通过免疫原设计和转基因小鼠和猕猴测试的循环来设计疫苗。 本 P01 拨款中提出的实验将产生候选免疫原用于测试 合作者马尔科姆·马丁博士在猕猴上进行了实验，并进行了人体疫苗试验。一项创新 该项目的一个方面是其结构测定和免疫原的综合方法 设计、选择和评估 - 解决结构的人员也参与其中 免疫原设计和筛选，实现快速、知情的迭代周期 免疫原的改善。 作为这种集成方法的一部分，Bjorkman 实验室开发了软件包 HIV 抗体数据库，旨在实现无障碍访问、比较、 广泛中和抗 HIV 抗体序列、结构和中和的分析 数据。该程序包括一个数据分析工具，用于识别 HIV-1 Env 序列特征 负责跨菌株的中和/结合效力变异。这个创新工具具有 允许我们使用结构组合来确定 Ab/Env 接口的关键相互作用 和生物信息学分析。我们建议通过以下方式增强艾滋病毒抗体数据库工具： 通过整合公开可用的数据流来提高其稳健性和可持续性， 采用标准格式进行结构数据的输入和输出，优化性能，以及 集成 Bjorkman 实验室开发的另一个程序 Variant Database，该程序可以 查询病毒突变景观。变异数据库可快速搜索SARS-CoV-2基因组 包含超过一百万个序列的数据集。因此，它可用于检测新出现的突变 传统系统发育分析中可能被忽视的模式。我们建议 概括变体数据库来分析不同的病毒分类群，包括 HIV-1。变体数据库 将得到增强，更加稳健和可持续，并且该版本将与 HIV 集成 抗体数据库。