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.

项目总结