Molecular mapping of SARS-CoV2 and the host response with multiomics mass spectrometry to stratify disease outcomes

该项目是了解COVID-19在全球人口中发病机制的国际努力的一部分。尽管在遗传水平上对SARS-CoV-2病毒有了相当大的了解，但病毒结构的关键方面及其致病作用仍有待确定。同样，导致疾病进展的分子描述符定义不清，尚未在检测策略中加以考虑。质谱（MS）可以在分子水平（多组学）上提供快速、精确和可重复的诊断信息，补充基因组信息。在这个项目中，我们将使用质谱分析患者对COVID-19的反应（来自NHS合作伙伴的样本）。这项研究将由我们的工业项目合作伙伴用于诊断/预后测试方案以及疫苗和治疗方法的开发。研究将构成英国在COVID-19 MS倡议的国际联盟中的努力，该联盟目前由28个国家的600多名成员发起，他们同意分享经验、方案、材料和数据。这种下一代测量方法既可转移又可获取，通过涉及多个合作伙伴实验室的重复研究，我们将克服当前基于实验室的方法的准确性和敏感性问题，同时还提供有关COVID-19个人风险的人群数据。与目前使用的间接实验室方法不同，我们的多组学方法可以利用内在物理特性（质量）获得病毒的详细结构信息及其对宿主的影响。产出是多方面的：我们将改进检测方法，对治疗方案进行分层，确定隔离要求，并在针对COVID-19和未来威胁的新型治疗开发规划的测量方面加快急需的速度。通过我们在生物标志物发现和验证方面的专业知识来描述疾病机制，我们拥有从数据中提取最大理解的处理管道。作为蛋白质结构分析领域的世界领导者，我们将从结构上描述病毒：细胞相互作用，为疫苗设计和治疗干预提供信息。所获得的知识将转化为医院检测实验室进行靶向分析，转化为生物制药公司开发疫苗和疗法，以及开发和质量控制生物标志物或血清学测试试剂。通过与LGC有限公司的诊断和测量公司（Waters, Thermo, Sciex, Bruker）以及CAMS分析和测量科学社区主要制药公司（辉瑞，阿斯利康，GSK和Allergan）的合作，我们将能够扩大我们的方法并将结果转化为为NHS提供生物标志物的靶向分析，验证血清学测试以及疫苗和治疗开发，以融入未来的弹性。国际努力有目的地在地理上分散，允许区域NHS实验室访问以实现快速实施。最后，我们建立了COVID-19 MS联盟，以共享样本处理方案，并使所有整理的数据集开放和可访问，以供全球努力抗击这一疾病。

This project forms part of an international level effort to understand the mechanisms of COVID-19 disease in the global population. Despite the considerable insight gained into the virus,SARS-CoV-2, at the genetic level, the key facets of the virus structure and its pathogenic effects remain to be determined. Equally molecular descriptors that contribute to disease progression are poorly defined, and have not yet been considered in testing strategies. Mass spectrometry (MS) can provide rapid, precise and reproducible diagnostic information at the molecular level (multiomics) that complements genomic information. In this project we will use MS to profile patient response to COVID-19 (with samples from NHS partners). This research will be exploited by our industrial project partners for diagnostic/prognostic testing protocols and for the development of vaccines and therapeutics. Research will constitute the UK effort in an international coalition initiated by the PI, COVID-19 MS, (currently over 600 members in 28 countries) who have agreed to share experience, protocols, materials and data. This next generation measurement approach is both transferable and accessible and through replication studies involving multiple partner labs we will overcome the accuracy, sensitivity issues of current lab- based approaches while also providing population data about individual risk to COVID-19. Our multiomics approach allows detailed structural information of the virus and its effect on the host using an intrinsic physical property - mass - unlike the indirect lab approaches currently employed. Outputs are multifold: we will refine testing approaches, stratify treatment options, determine isolation requirements and bring much needed speed into measurement aspects of novel therapeutic development programmes - for COVID-19 and future threats.Through our expertise in biomarker discovery and validation to profile disease mechanisms we possess the processing pipelines to extract maximum understanding from the data. As world leaders in protein structure analysis, we will structurally characterise virus:cell interactions, informing vaccine design and therapeutic intervention. Knowledge gained will be translatable to hospital testing laboratories for targeted assays, to biopharmaceutical companies for vaccine and therapeutics development, and for the development and quality control of reagents for biomarker or serological tests. Working with LGC Ltd. diagnostics and measurement companies (Waters, Thermo, Sciex, Bruker) and through CAMS the Community for Analytical and Measurement Science major Pharmaceutical companies (Pfizer, AstraZeneca , GSK, and Allergan) we will be able to scale up our methods and translate the outcomes to provide targeted assays to the NHS for biomarkers, to validate serological tests and for vaccine and therapeutic development embedding future resilience. The international effort is purposefully geographically spread allowing regional NHS lab access to enable rapid implementation. Finally, we established the COVID-19 MS Coalition to share sample processing protocols and to make all curated datasets open and accessible for global effort to combat this disease.