Technology and Computational Core

技术与计算核心

• 批准号: 10328118
• 负责人: Alexandra-Chloe Villani
• 金额: $ 174.61万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328118
• 关键词: 2019-nCoV; Algebra; Algorithms; Amino Acid Sequence; Base Sequence; Biological; Biological Models; Blood; Blood specimen; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Chemistry; Clinical; Clonal Expansion; Collaborations; Complex; Computer Analysis; Computer Models; Computing Methodologies; Coronavirus; Data; Data Analyses; Data Set; Development; Disease; Ecosystem; Emulsions; Engineering; Ensure; Epitopes; Experimental Designs; Future; Gene Expression Profiling; Generations; Genetic Transcription; Genomic approach; Genomics; Goals; Immune; Immune response; Immunity; Immunization; Immunize; Immunological Models; Immunologist; Infection; Lung; Machine Learning; Measurement; Membrane Proteins; Methods; Modeling; Molecular; Mus; Nature; Pathway interactions; Phenotype; Population; Publications; RNA; Recording of previous events; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; SARS-CoV-2 variant; Scientist; Specimen; Standardization; Structure of parenchyma of lung; System; T-Lymphocyte; Techniques; Technology; Testing; Therapeutic; Tissue Sample; Tissue-Specific Gene Expression; Tissues; Vaccines; Variant; Virus; Work; antigen antibody binding; base; cell type; computer science; coronavirus vaccine; data integration; design; experimental analysis; experimental study; genomic data; human subject; innovation; insight; machine learning method; multidisciplinary; next generation; novel; pandemic disease; pathogen; prevent; programs; receptor; response; single cell analysis; single-cell RNA sequencing; stem; success; universal coronavirus vaccine; working group

PROJECT SUMMARY CORE B The goal of this Program Project is to bring together a multi-disciplinary team to produce information necessary for the design and testing of the next-generation of CoV vaccine strategies that will have the greatest possible breadth across other CoVs. Results from all three projects will inform design of Pan-Coronavirus vaccines against evolving SARS-CoV-2 variants and other coronaviruses to stem current and prevent future pandemics. This will be accomplished through three dynamic and integrative projects examining various key aspects of vaccine strategies. The Technology and Computational Core B will support, in close interaction with each of the other investigators, all three Projects to gain maximal insight from the proposed experimental work. Based on the need for centralized tissue and blood processing, single-cell genomics and TCR sequencing data generation, and integrative computational analyses, we hypothesized that having a central Technology and Computational Core, as opposed to having each project working independently, will be critical to the success of the work proposed in this Program application and will maximize comparisons and integration of data across projects. A centralized working group of immunologists, sequencing experts, and computational biologists is the best way to ensure that this research will be properly carried out with maximal identification and use of appropriate computational methods. Through Aim 1, Core B will support all three Research Projects by providing expert advice and assistance on executing single-cell genomics and TCR sequencing experimental and analytical strategies of blood and tissue specimens collected from human subjects and lung from immunized mice. The standardized frameworks provided by the Core staff will add rigor and reproducibility to all experiments by removing any variation that might otherwise arise. Core B will also provide collaborative efforts on multi-variate modeling of immune system response and antigen/antibody binding (Aim 2). Because of the complexity of immune responses to pathogens, our ability to gain insights and principles from the experimental datasets generated across all three Projects will be enhanced by integrative computational analysis and modeling embracing an integrative systems perspective. This complexity derives from diverse issues including: (a) concomitant contributions from multiple variables together govern observed responses, rather than any single variable being determinative by itself; (b) these multi-variate contributions are generally not independent, but instead are typically co- or anti-correlated; and (c) these contributions often are non-linear in nature. Most standard statistical techniques typically violate one or more of these issues, so the purpose of this Core is to apply computational approaches arising from engineering and computer science, including “machine learning” techniques, that can in fact accommodate any or all of them. Finally, Core B will provide additional assistance for any complicated experimental design or analysis if/as needed. To aid with transparency, all data and analysis frameworks supporting all findings will be made publicly available upon acceptance for publication.

项目概要核心B 本计划项目的目标是汇集一个多学科的团队，以产生必要的信息 用于设计和测试下一代冠状病毒疫苗策略， 在其他COV中的广度。所有三个项目的结果将为泛冠状病毒疫苗的设计提供信息 对抗不断演变的SARS-CoV-2变种和其他冠状病毒，以遏制当前和预防未来的大流行。 这将通过三个充满活力的综合项目来实现， 疫苗战略。技术和计算核心B将通过与 其他研究人员，所有三个项目，以获得最大的洞察力，从拟议的实验工作。基于 需要集中的组织和血液处理，单细胞基因组学和TCR测序数据生成， 和综合计算分析，我们假设，有一个中央技术和计算 核心，而不是让每个项目独立工作，将是至关重要的工作的成功 在本计划申请中提出，并将最大限度地比较和整合项目之间的数据。一 由免疫学家、测序专家和计算生物学家组成的集中工作组是最好的方法 以确保这项研究将适当进行，最大限度地识别和使用适当的 计算方法通过目标1，核心B将通过提供专家支持所有三个研究项目。 在执行单细胞基因组学和TCR测序实验和分析方面提供建议和协助 从人类受试者收集的血液和组织样本以及从免疫小鼠收集的肺的策略。的 核心人员提供的标准化框架将增加所有实验的严谨性和可重复性， 消除了可能出现的任何变化。核心B还将在多变量 免疫系统应答和抗原/抗体结合的建模（目标2）。的复杂性 对病原体的免疫反应，我们从实验数据集中获得见解和原理的能力 通过综合计算分析和建模， 采用综合系统的观点。这种复杂性来自各种问题，包括： 多个变量的共同贡献共同决定了观察到的响应，而不是任何单一的 变量本身是决定性的;（B）这些多变量贡献通常不是独立的，但是 而是典型地是共相关或反相关的;以及（c）这些贡献在本质上通常是非线性的。最 标准的统计技术通常会违反这些问题中的一个或多个，因此本核心的目的是 应用来自工程和计算机科学的计算方法，包括“机器学习” 技术，事实上可以容纳任何或所有这些。最后，核心B将提供额外援助 任何复杂的实验设计或分析，如果/根据需要。为了提高透明度，所有数据和分析 支持所有调查结果的框架将在接受出版后公布。