Immune repertoire sequencing: error correction, analysis, and visualization on the cloud

免疫组库测序：云端纠错、分析和可视化

• 批准号: 10010744
• 负责人: Natalie Castellana
• 金额: $ 21.73万
• 依托单位: DIGITAL PROTEOMICS LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2021-05-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010744
• 关键词: Academia; Adaptive Immune System; Address; Algorithmic Analysis; Algorithms; Alpaca; Animal Model; Antibodies; Antibody Repertoire; Autoimmune Diseases; B-Lymphocytes; Base Sequence; Benchmarking; Biological Assay; Cells; Chickens; Client; Cloud Computing; DNA Sequencing Facility; Data; Data Analyses; Data Set; Decision Making; Disease; Excision; Foundations; Gene Conversion; Gene Mutation; Genes; Genetic Recombination; Genomics; Goals; Graph; Human; Immune; Immune response; Immune system; Immunology; Individual; Industry; Informatics; Internet; Length; Light; Literature; Llama; Malignant Neoplasms; Metadata; Methods; Molecular; Mus; Mutation; Mutation Analysis; Nucleotides; Online Systems; Organism; Oryctolagus cuniculus; Outcome; Pharmaceutical Preparations; Phase; Population; Population Heterogeneity; Preparation; Process; Proteomics; Protocols documentation; Reporting; Research Personnel; Sampling; Secure; Serum; Services; Structure; Technology; Transgenic Animals; Visualization; algorithm development; analysis pipeline; assay development; base; cloud platform; computerized data processing; computing resources; cost; digital; drug discovery; experimental study; improved; innovation; interest; nanobodies; next generation sequencing; novel; pathogen; research and development; response; tool; transcriptomics; tumor microenvironment; vaccine development; vaccine response

Project Summary Antibodies are vital molecules produced by the adaptive immune system, and are a critical component in identifying foreign agents for removal within an organism. Produced by B cells, antibodies have an enormously diverse set of possible compositions, created by somatic recombination and hypermutation processes that are specific to these types of immune cells. Due to their incredible diversity, studying them for the purpose of antibody discovery or disease characterization, becomes a difficult task. Recently, next-generation sequencing (NGS) technologies have been successfully applied to study the diverse repertoire of antibodies produced by B cells. This technology has proven incredible for understanding this component of the immune response in a new level of detail. Unfortunately, NGS produced strings contain errors as part of the process. These errors can be confused as true sequence diversity, and can confound downstream analysis and interpretation. Furthermore, structuring such deep sequenced antibody repertoire data for answering questions about the immune response is non-trivial and compute resource intensive; problems that not many labs are well suited to address. Our proposal seeks to break down barriers for entry of these repertoire sequencing assays by providing innovative informatics approaches to error correction and analysis, delivering results in an interactive cloud platform. Our service will be the first to offer non-human/mouse species support, as well as support for transgenic animals, critical for many drug discovery companies.

项目摘要 抗体是由自适应免疫系统产生的重要分子，是一种 识别出生物体中去除外国代理的关键组成部分。由b 细胞，抗体具有大量不同的可能组成，由体细胞产生 针对这些类型的免疫细胞的重组和超数过程。 由于它们令人难以置信的多样性，因此研究它们是为了发现抗体或疾病的目的 表征，成为一项艰巨的任务。 最近，下一代测序（NGS）技术已成功 应用于研究B细胞产生的抗体的多种曲目。这项技术有 被证明令人难以置信的是理解免疫反应的这一组成部分 细节。不幸的是，NGS产生的字符串包含错误作为过程的一部分。这些错误 可以混淆为真实的序列多样性，并且可以混淆下游分析和 解释。此外，构建如此深的测序抗体库数据 回答有关免疫反应的问题是不平凡的，计算资源密集型； 没有很多实验室的问题非常适合解决。 我们的建议旨在打破进入这些曲目测序的障碍 通过提供创新的信息学方法来纠正和分析，测定法， 在交互式云平台中提供结果。我们的服务将是第一个提供的服务 非人类/小鼠物种的支持，以及对转基因动物的支持，对许多人至关重要 毒品发现公司。