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EAGER: Assembling the Immunoglobulin Loci Across Mammalian Species and Across the Human Population

EAGER：组装哺乳动物物种和人类群体的免疫球蛋白位点

基本信息

批准号：
2032783
负责人：
Pavel Pevzner
金额：
$ 30万
依托单位：
University of California-San Diego
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2032783&HistoricalAwards=false
关键词：
EAGER Assembling Immunoglobulin Loci Across

项目摘要

The ongoing COVID-19 pandemic raised the challenge of developing new computational techniques for understanding the immune response to emerging pathogens. This project will develop a new computer program for analyzing the parts of the genome that are responsible for immune responses to pathogens. This will enable analyses of the development of immunity to the virus in human populations by characterizing the mutations that are essential to the immune response. This research will also enhance understanding of the immune responses in bats, which are hosts to large numbers of coronaviruses, and in llamas, which are potentially an important source for a robust vaccine against the virus. The project will also develop a Massive Online Open Course “Bioinformatics of SARS-COV-2” that will cover various aspects of computational analysis of emerging pathogens, and the challenges of analyzing these complex and dynamic parts of the human genome. Information about the immunoglobulin-encoding regions in the genome is critically important for analyzing the immune response to the novel SARS-CoV-2 coronavirus, developing antibody drugs against SARS-COV-2, and testing future vaccines against SARS-CoV-2. However, there are still no algorithms for inferring the sequences of the highly complex and rapidly evolving immunoglobulin (IG) loci. Moreover, although the immunoglobulin genes within the IG loci form the building blocks of antibodies, there are still no software tools for accurate identification of these genes. This project will develop a new algorithm for assembling and annotating the IG loci. These methods will be applied to multiple mammalian genomes with a focus on assembling the unusually complex IG loci in bats to characterize their immune response to coronaviruses. A second focus will be assembly of camelid IG loci to aid in developing vaccines against SARS-COV-2, taking advantage of the simpler and more stable antibodies present in this group. The project will also focus on assembling the highly variable immunoglobulin loci in multiple COVID-19 patients with the goal of revealing functionally important mutations in these loci. The project entails substantial risk, because the IG loci have been recalcitrant to all previous assembly attempts, but enhanced understanding of mammalian immunoglobin genes would greatly enhance the ability of society to predict and respond to current and future pandemics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

持续的COVID-19大流行提出了开发新的计算技术以了解对新兴病原体的免疫反应的挑战。该项目将开发一种新的计算机程序，用于分析负责对病原体免疫反应的基因组部分。这将通过描述对免疫反应至关重要的突变，分析人类对病毒的免疫力发展。这项研究还将加强对蝙蝠免疫反应的理解，蝙蝠是大量冠状病毒的宿主，而美洲驼可能是对抗该病毒的强大疫苗的重要来源。该项目还将开发一个大规模在线开放课程“SARS-COV-2的生物信息学”，该课程将涵盖新兴病原体计算分析的各个方面，以及分析人类基因组这些复杂和动态部分的挑战。关于基因组中免疫球蛋白编码区的信息对于分析对新型SARS-CoV-2冠状病毒的免疫反应、开发针对SARS-CoV-2的抗体药物以及测试针对SARS-CoV-2的未来疫苗至关重要。然而，仍然没有算法来推断高度复杂和快速进化的免疫球蛋白（IG）基因座的序列。此外，尽管IG基因座内的免疫球蛋白基因形成抗体的构建模块，但仍然没有软件工具用于准确识别这些基因。本计画将发展一种新的演算法来组装和注解IG基因座。这些方法将应用于多种哺乳动物基因组，重点是组装蝙蝠中异常复杂的IG基因座，以表征它们对冠状病毒的免疫反应。第二个重点将是骆驼IG基因座的组装，以帮助开发针对SARS-COV-2的疫苗，利用该组中存在的更简单和更稳定的抗体。该项目还将专注于组装多名COVID-19患者的高度可变免疫球蛋白基因座，目的是揭示这些基因座中功能重要的突变。该项目承担着巨大的风险，因为IG基因座已经被所有以前的组装尝试所否定，但对哺乳动物免疫球蛋白基因的深入了解将大大提高社会对当前和未来流行病的预测和应对能力。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。