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.

项目摘要核心B 该计划项目的目标是汇集一个多学科团队，以产生必要的信息 为了设计和测试COV疫苗策略的下一代，这些策略将拥有最大的可能 其他COV的宽度。所有三个项目的结果都将为泛氧化病毒疫苗的设计提供信息 反对不断发展的SARS-COV-2变体和其他冠状病毒，以阻止电流并防止未来的大流行。 这将通过三个动态和综合项目来完成，研究的各个关键方面 疫苗策略。技术和计算核心B将与每一个 其他研究人员，这三个项目旨在从拟议的实验工作中获得最大见解。基于 需要集中组织和血液处理，单细胞基因组学和TCR测序数据生成， 以及集成的计算分析，我们假设拥有中央技术和计算 核心，而不是让每个项目独立工作，对工作的成功至关重要 在此程序应用程序中提出的，将最大程度地提高项目跨项目的比较和集成。一个 免疫学家，测序专家和计算生物学家的集中工作组是最好的方法 确保将这项研究适当地进行，并最大程度地识别和使用适当 计算方法。通过AIM 1，Core B将通过为专家提供专家来支持所有三个研究项目 有关执行单细胞基因组学和TCR测序实验和分析的建议和帮助 从人类受试者和免疫小鼠中收集的血液和组织标本策略。这 核心人员提供的标准化框架将通过 删除可能发生的任何变化。核心B还将为多变量提供协作努力 免疫系统反应和抗原/抗体结合的建模（AIM 2）。由于复杂性 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 通过集成的计算分析和建模将增强所有三个项目的生成 拥抱集成系统的观点。这种复杂性来自潜水员问题，包括：（a） 来自多个变量的伴随贡献共同控制观察到的响应，而不是任何一个单一的响应 变量被自身确定； （b）这些多变量贡献通常不是独立的，而是 相反，通常是共同或反相关的； （c）这些贡献通常是非线性的。最多 标准统计技术通常违反其中一个或多个问题，因此该核心的目的是 应用工程和计算机科学引起的计算方法，包括“机器学习” 技术实际上可以容纳任何一个或全部。最后，核心B将提供额外的帮助 对于任何复杂的实验设计或分析，如果/需要/分析。为了帮助透明度，所有数据和分析 支持所有发现的框架将在接受后公开提供。