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.

项目摘要 我们P01 Hivrad项目的目的是推进我们针对HIV-1的种系目标的方法 通过免疫原设计和测试的转基因小鼠和猕猴的疫苗设计。 本P01赠款中提出的实验将产生候选免疫原以进行测试 合作者Malcolm Martin博士和人类疫苗试验的猕猴。一个创新的 该项目的方面是其结构确定和免疫原的综合方法 设计，选择和评估 - 解决结构的同一个人也涉及 免疫原设计和筛查，允许迭代的快速而知情的周期 免疫原子的改善。 作为这种综合方法的一部分，Bjorkman Lab开发了软件包 HIV抗体数据库旨在使无摩擦访问能够访问，比较 以及广泛中和抗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，以识别HIV-1 Env序列功能 负责跨菌株的中和/结合效力变异性。这个创新工具具有 允许我们使用结构的组合来确定AB/Env界面的关键相互作用 和生物信息学分析。我们建议通过 通过整合可公开可用的数据流来改善其鲁棒性和可持续性， 采用标准格式，以进行结构数据的输入和输出，优化性能和 整合由Bjorkman Lab开发的另一个程序，Variant Database，可以 查询病毒突变景观。变体数据库可以快速搜索SARS-COV-2基因组 数据集超过一百万个序列。因此，它可用于检测新出现的突变 在常规系统发育分析中可能会忽略的模式。我们建议 概括变体数据库，以分析包括HIV-1在内的不同病毒类群。变体数据库 将得到增强以更加健壮和可持续，此版本将与艾滋病毒融为一体 抗体数据库。