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.

项目概要 抗体是适应性免疫系统产生的重要分子，是一种 识别生物体内的外来物质并清除的关键组成部分。制作者：B 细胞中，抗​​体具有由体细胞产生的极其多样化的可能成分 这些类型的免疫细胞特有的重组和超突变过程。 由于它们令人难以置信的多样性，为了发现抗体或疾病而研究它们 表征，成为一项艰巨的任务。 最近，新一代测序（NGS）技术已成功 用于研究 B 细胞产生的多种抗体。这项技术有 事实证明，对于以新的水平理解免疫反应的这一组成部分是令人难以置信的 细节。不幸的是，NGS 生成的字符串在过程中包含错误。这些错误 可能会被混淆为真正的序列多样性，并且可能会混淆下游分析和 解释。此外，构建此类深度测序的抗体库数据 回答有关免疫反应的问题并非易事，并且需要大量计算资源； 没有多少实验室能够很好地解决这些问题。 我们的建议旨在打破这些曲目测序的进入障碍 通过提供创新的信息学方法来进行纠错和分析， 在交互式云平台中交付结果。我们的服务将是第一个提供 非人类/小鼠物种的支持以及对转基因动物的支持，对许多人来说至关重要 药物发现公司。