RAPID: finding virulence genes as therapeutic targets in Covid-19

RAPID：寻找毒力基因作为 Covid-19 的治疗靶点

• 批准号: 2029595
• 负责人: Jonathan Arnold
• 金额: $ 20万
• 依托单位: University of Georgia Research Foundation Inc
• 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: 2020-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029595&HistoricalAwards=false
• 关键词: RAPID; finding; virulence; genes; therapeutic

This RAPID award is made by the Division of Biological Infrastructure (DBI) using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act. This award to the University of Georgia will leverage bioinformatics tools to identify virulence genes that assisted SARS-COV-2 in jumping species boundaries. Identifying shared genetic changes between human SARS-COV-2 and its relatives in mammalian reservoirs in the bat, pangolin, and civit is important to understanding the virus mode of action. It is especially critical to identify which of the changes contribute to human virulence of SARS-COV-2. The researchers will analyze 3200+ genomes from SARS-COV-2 and coronavirus genomes from animal reservoirs to look at genetic changes associated with virulence and COVID-19 symptoms. To accomplish this work, new software tools will be developed to better leverage modern computer graphics processing units (GPUs) for high-speed parallel computing. The project will engage graduate students and REU participants in interdisciplinary research of critical national importance and contribute useful tools for future bioinformatic research.The objective of this project is to identify virulence genes that enable SARS-COV-2 to jump species boundaries from vertebrate reservoirs. The project has three main components: (1) building gene trees within species trees of coronavirus by coalescent methods; (2) testing for shared polymorphisms under selective sweep between natural reservoirs and human SARS-COV-2; (3) validating candidates identified in task (2) independently by comparing gene genealogies for selective sweep (under selection for virulence) vs. incomplete lineage sorting. An interdisciplinary team from genetics, bioinformatics, and infectious diseases will develop gene trees within a species tree of 3,200+ published SARS-COV-2 genomes using a novel BEST coalescent method developed for GPUs. Results from these studies will be rapidly disseminated and published in peer-reviewed journals, presented at scientific conferences, and made available through shared software repositories.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.

该RAPID奖由生物基础设施部（DBI）使用《冠状病毒援助、救济和经济安全（CARES）法案》的资金颁发。该奖项授予佐治亚大学，将利用生物信息学工具识别帮助SARS-COV-2跨越物种界限的毒力基因。确定人类SARS-COV-2及其在蝙蝠、穿山甲和公民等哺乳动物宿主中的近亲之间的共同遗传变化对于了解病毒的作用模式非常重要。特别重要的是要确定哪些变化有助于SARS-COV-2的人类毒力。研究人员将分析来自动物宿主的SARS-COV-2和冠状病毒基因组的3200多个基因组，以研究与毒力和COVID-19症状相关的遗传变化。为了完成这项工作，将开发新的软件工具，以更好地利用现代计算机图形处理单元（gpu）进行高速并行计算。该项目将吸引研究生和REU参与者参与具有重要国家意义的跨学科研究，并为未来的生物信息学研究提供有用的工具。该项目的目的是鉴定使SARS-COV-2能够从脊椎动物宿主跨越物种界限的毒力基因。该项目主要有三个组成部分：(1)利用聚结法在冠状病毒种树内构建基因树；(2)检测自然宿主与人类SARS-COV-2在选择性扫描下的共享多态性；(3)通过比较选择性扫描（在毒力选择下）和不完全谱系分类的基因谱系，独立验证任务(2)中确定的候选基因。一个来自遗传学、生物信息学和传染病的跨学科团队将使用为gpu开发的新型BEST聚结方法，在3200多个已发表的SARS-COV-2基因组的物种树中开发基因树。这些研究的结果将迅速传播并发表在同行评议的期刊上，在科学会议上提出，并通过共享软件库提供。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。