RAPID Ebola outbreak: A Web Tool for Tracking Pathogen Evolution Impact on Immune Responses

埃博拉病毒快速爆发：追踪病原体进化对免疫反应影响的网络工具

• 批准号: 1509575
• 负责人: Sergei Pond
• 金额: $ 20万
• 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: 2014
• 资助国家: 美国
• 起止时间: 2014-12-15 至 2015-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1509575&HistoricalAwards=false
• 关键词: RAPID; Ebola; outbreak; Web; Tool

The current Ebola outbreak, similar to the swine-origin influenza outbreak of 2009, is characterized by emergence of new strains of viruses that have previously circulated in animal reservoirs and gained the ability for human-to-human transmission. As the virus adapts to this new mode of transmission, multiple mutations occur. Thus, data from previous studies of the parent virus might no longer be relevant. This recurring situation of viruses mutating as they adapt makes it necessary to develop tools to rapidly re-analyze existing data for their relevance as new sequences of circulating strains become available. The focus of this project is to provide such a tool for monitoring the effect of mutations in protein sites of immune recognition, also known as epitopes, in a given pathogen. Applied to Ebola virus, the proposed tool will have an immediate impact on addressing in real time, as the virus evolves, the need for monitoring and developing new products for treating, preventing, and diagnosing Ebola. This project has three goals: (1) To develop a web tool that will take as input new pathogen sequences and, in the case of Ebola, automatically gather them from GenBank. These sequences will be cross-compared for epitope data in the IEDB (Immune Epitope Database), and conservancy analysis will be run on known and predicted epitopes. (2) To connect the tool to the University of California Santa Cruz (UCSC) Genome Browser to allow visualizing protein and epitope data. (3) To incorporate into and make the tool available on the IEDB website to ensure sustainability and broader access.The project is focused on basic research on how pathogen evolution impacts recognition by the host immune system. The tool, which will simultaneously capture, monitor, analyze, and visualize in real time data on pathogen evolution and immune epitopes, should allow the researchers to address questions such as which pathogen proteins and signature sites in proteins enable pathogen evolution and adaptation; do new mutations change antigenic properties of pathogen proteins; and how do mutation affect the molecular recognition of pathogen antigens by the immune receptors. The tool will enable rapid monitoring of any emerging virus strain and provide insight on how mutations affect conservancy of known epitopes and antigenicity of the virus. The B and T cell epitopes for each viral protein will be predicted using the IEDB Analysis Resource and be provided to the community for further investigation of potential peptide-based products (therapeutics, vaccines, diagnostics). Integration with the UCSC Genome Browser and IEDB will provide high visibility and broader access to the tool. The proposed tool will be applicable to a wide range of pathogens, ensuring the community preparedness for a rapid response to future outbreaks. The project will also broaden participation of under-represented groups in science, will be integrated into courses the PI teaches and will be integrated into the PI?s outreach activities, including mentoring high-school students. A workshop and lectures on the project?s topic will be given to K-12 teachers and students through the SDSC educational programs TeacherTECH and StudentTECH.

目前的埃博拉疫情类似于2009年的猪源流感疫情，其特点是出现了新的病毒株，这些病毒以前在动物宿主中传播，并获得了在人与人之间传播的能力。当病毒适应这种新的传播模式时，就会发生多种突变。因此，以前对母体病毒的研究数据可能不再相关。病毒随着适应而变异的这种反复出现的情况，使得有必要开发工具，随着新的流行毒株序列的出现，快速重新分析现有数据与它们的相关性。该项目的重点是提供这样一种工具，用于监测特定病原体中免疫识别蛋白位点突变的影响，也称为表位。将拟议的工具应用于埃博拉病毒，将立即产生影响，随着病毒的演变，实时解决监测和开发治疗、预防和诊断埃博拉病毒的新产品的需求。该项目有三个目标：(1)开发一个网络工具，它将接受新的病原体序列作为输入，并在埃博拉病毒的情况下，自动从GenBank收集它们。这些序列将与IEDB(免疫表位数据库)中的表位数据进行交叉比较，并将对已知和预测的表位进行保守性分析。(2)将该工具连接到加州大学圣克鲁斯分校(UCSC)基因组浏览器，以实现蛋白质和表位数据的可视化。(3)将该工具纳入IEDB网站并在其上提供，以确保可持续性和更广泛的访问。该项目侧重于病原体进化如何影响宿主免疫系统识别的基础研究。该工具将同时捕获、监测、分析和实时可视化病原体进化和免疫表位的数据，应该允许研究人员解决以下问题：哪些病原体蛋白质和蛋白质中的签名位置使病原体进化和适应；新的突变是否会改变病原体蛋白质的抗原性；突变如何影响免疫受体对病原体抗原的分子识别。该工具将能够快速监测任何新出现的病毒株，并提供关于突变如何影响已知表位的保守性和病毒的抗原性的洞察力。将使用IEDB分析资源预测每种病毒蛋白的B和T细胞表位，并将其提供给社区，用于进一步研究潜在的基于多肽的产品(治疗、疫苗、诊断)。与UCSC Genome浏览器和IEDB的集成将提供对该工具的高度可见性和更广泛的访问。拟议的工具将适用于广泛的病原体，确保社区为未来疫情的快速反应做好准备。该项目还将扩大未得到充分代表的群体对科学的参与，将被纳入国际和平协会教授的课程，并将被纳入国际和平协会？S外联活动，包括指导高中生。通过SDSC的TeacherTECH和StudentTECH教育项目，将为K-12教师和学生举办关于项目？S主题的研讨会和讲座。