Development of a Clinical MALDI-ToF Mass Spectrometry Assay for SARS-CoV-2: Rational Design and Multi-Disciplinary Team Work.

Development of a Clinical MALDI-ToF Mass Spectrometry Assay for SARS-CoV-2: Rational Design and Multi-Disciplinary Team Work.
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DOI:
10.3390/diagnostics10100746
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发表时间:
2020-09-24
期刊:
Diagnostics (Basel, Switzerland)
影响因子:
--
通讯作者:
Heeney JL
Heeney JL
中科院分区:
其他
文献类型:
--
作者:
Iles RK;Zmuidinaite R;Iles JK;Carnell G;Sampson A;Heeney JL

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由SARS-CoV-2冠状病毒引起的COVID-19大流行使世界上几乎所有国家的国家检测能力都达到了极限。为控制感染的传播,迅速对一个国家的大量人口进行筛查的必要性是至关重要的。然而,基于RT-PCR的检测(目前的一线检测)对试剂供应(和相关成本)的后勤要求存在很大问题。基于质谱的方法使用拭子和含漱液样本已经被报道有希望,但还没有从整个诊断过程的系统分析中接近任务。在这里,从样品处理、人体生物流体中病原体的生物学特性、下游生物和物理化学以及所有重要的数据处理、临床解释和报告,都被仔细地汇编成一个单一的高通量和可重复的快速过程。利用MALDI-ToF质谱检测病毒包膜糖蛋白的系统生物学多学科团队方法,我们已经实现了多方面的临床MALDI-ToF质谱筛选试验,主要(但不限于)SARS-CoV-2,并直接应用于未来可能出现的其他流行病/大流行。产生的临床信息不仅包括SARS-CoV-2冠状病毒检测- (Spike蛋白片段S1、S2b、S2a峰),还包括检测到的其他呼吸道病毒感染,以及口腔上呼吸道免疫反应的一般评估(总Ig轻链峰升高)和病毒免疫反应的测量(IgA重链峰强度升高)。该方法的优点包括:(1)取样方便,(2)分析速度快,并且大大降低了测试成本。这些特点揭示了MALDI-ToF质谱法作为一种强大而经济的全球解决方案的诊断效用
The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has stretched national testing capacities to breaking points in almost all countries of the world. The need to rapidly screen vast numbers of a country’s population in order to control the spread of the infection is paramount. However, the logistical requirement for reagent supply (and associated cost) of RT-PCR based testing (the current front-line test) have been hugely problematic. Mass spectrometry-based methods using swab and gargle samples have been reported with promise, but have not approached the task from a systematic analysis of the entire diagnostic process. Here, the pipeline from sample processing, the biological characteristics of the pathogen in human biofluid, the downstream bio- and physical-chemistry and the all-important data processing with clinical interpretation and reporting, are carefully compiled into a single high-throughput and reproducible rapid process. Utilizing MALDI-ToF mass spectrometric detection to viral envelope glycoproteins in a systems biology-multidisciplinary team approach, we have achieved a multifaceted clinical MALDI ToF MS screening test, primarily (but not limited to) SARS-CoV-2, with direct application to other future epidemics/pandemics that may arise. The clinical information generated not only includes SARS-CoV-2 coronavirus detection–(Spike protein fragments S1, S2b, S2a peaks), but other respiratory viral infections detected as well as an assessment of generalised oral upper respiratory immune response (elevated total Ig light chain peak) and a measure of the viral immune response (elevated intensity of IgA heavy chain peak). The advantages of the method include; (1) ease of sampling, (2) speed of analysis, and much reduced cost of testing. These features reveal the diagnostic utility of MALDI-ToF mass spectrometry as a powerful and economically attractive global solution
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