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

利用多组学质谱分析 SARS-CoV2 的分子图谱和宿主反应，对疾病结果进行分层

• 批准号: BB/V011456/1
• 负责人: Perdita Barran
• 金额: $ 221.2万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV011456%2F1
• 关键词: Molecular; mapping; SARS; CoV2; host

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.

该项目是国际层面努力了解全球人口中COVID-19疾病机制的一部分。尽管在基因水平上对SARS-CoV-2病毒有了相当深入的了解，但病毒结构的关键方面及其致病作用仍有待确定。同样，有助于疾病进展的分子描述符定义不明确，并且尚未在测试策略中考虑。质谱（MS）可以在分子水平（多组学）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MS来分析患者对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/预后测试协议以及疫苗和治疗药物的开发。研究将构成英国在PI发起的国际联盟中的努力，COVID-19 MS（目前在28个国家有600多名成员）已同意分享经验，方案，材料和数据。这种下一代测量方法既可转移又可访问，通过涉及多个合作伙伴实验室的复制研究，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。我们的多组学方法允许病毒的详细结构信息及其对宿主的影响，使用固有的物理特性-质量-与目前采用的间接实验室方法不同。输出是多方面的：我们将完善检测方法，对治疗方案进行分层，确定隔离要求，并为新型治疗开发计划的测量方面带来急需的速度-针对COVID-19和未来的威胁。通过我们在生物标志物发现和验证方面的专业知识，我们拥有处理管道，可以从数据中提取最大程度的理解。作为蛋白质结构分析的世界领导者，我们将从结构上研究病毒：细胞相互作用，为疫苗设计和治疗干预提供信息。所获得的知识将可转化为医院检测实验室进行靶向检测，转化为生物制药公司进行疫苗和治疗方法开发，以及生物标志物或血清学检测试剂的开发和质量控制。与LGC有限公司合作诊断和测量公司（沃茨、Thermo、Sciex、Bruker），并通过CAMS与主要制药公司的分析和测量科学共同体合作（辉瑞，阿斯利康，GSK和Allergan）我们将能够扩大我们的方法，并将结果转化为NHS的生物标志物，以验证血清学测试，并为疫苗和治疗开发嵌入未来的复原力。国际努力有目的地在地理上分布，允许区域NHS实验室访问，以实现快速实施。最后，我们成立了COVID-19 MS联盟，以分享样本处理协议，并使所有策划的数据集开放并可供全球抗击这种疾病的努力使用。

项目成果

Metabolomics Markers of COVID-19 Are Dependent on Collection Wave.

• DOI: 10.3390/metabo12080713
• 发表时间: 2022-07-30
• 期刊: Metabolites
• 影响因子: 4.1

Untargeted saliva metabolomics by liquid chromatography-Mass spectrometry reveals markers of COVID-19 severity.

• DOI: 10.1371/journal.pone.0274967
• 发表时间: 2022
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Frampas, Cecile F.;Longman, Katie;Spick, Matt;Lewis, Holly-May;Costa, Catia D. S.;Stewart, Alex;Dunn-Walters, Deborah;Greener, Danni;Evetts, George;Skene, Debra J.;Trivedi, Drupad;Pitt, Andy;Hollywood, Katherine;Barran, Perdita;Bailey, Melanie J.
• 通讯作者: Bailey, Melanie J.

CSF1R defines the mononuclear phagocyte system lineage in human blood in health and COVID-19.

• DOI: 10.1093/immadv/ltab003
• 发表时间: 2021-01
• 期刊: Immunotherapy advances
• 作者: Combes TW;Orsenigo F;Stewart A;Mendis ASJR;Dunn-Walters D;Gordon S;Martinez FO
• 通讯作者: Martinez FO

Assessing Antigen Structural Integrity through Glycosylation Analysis of the SARS-CoV-2 Viral Spike.

• DOI: 10.1021/acscentsci.1c00058
• 发表时间: 2021-04-28
• 期刊: ACS central science
• 影响因子: 18.2
• 作者: Brun J;Vasiljevic S;Gangadharan B;Hensen M;V Chandran A;Hill ML;Kiappes JL;Dwek RA;Alonzi DS;Struwe WB;Zitzmann N
• 通讯作者: Zitzmann N

No skin off your back: the sampling and extraction of sebum for metabolomics.

• DOI: 10.1007/s11306-023-01982-3
• 发表时间: 2023-03-24
• 期刊: Metabolomics : Official journal of the Metabolomic Society