通过基于 omics 的方法对受 SARS-CoV-2 感染的患者唾液进行分子指纹分析。

IF 1.9 3区 化学 Q3 BIOCHEMICAL RESEARCH METHODS
Gabriella Pinto, Monica Gelzo, Gustavo Cernera, Mariapia Esposito, Anna Illiano, Stefania Serpico, Biagio Pinchera, Ivan Gentile, Giuseppe Castaldo, Angela Amoresano
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引用次数: 0

摘要

冠状病毒病2019(COVID-19)感染的临床表现千变万化,既有致命病例,也有症状轻微、病情迅速缓解的患者。我们通过整合大规模蛋白质组学、肽组学和靶向代谢组学,研究了 63 名住院的 COVID-19 患者和 30 名健康对照者的唾液,以评估感染后的生化变化,并获得一组有助于无创诊断的假定生物标志物。我们采用非靶向方法,使用液相色谱-串联质谱(LC-MS/MS)进行蛋白质组学和肽组学分析,并使用靶向液相色谱-多反应监测/质谱进行氨基酸分析。77 种蛋白质的水平在 COVID-19 患者中存在显著差异。其中,有 7 种蛋白质仅在 COVID-19 患者的唾液中发现,与对照组相比,有 4 种蛋白质在 COVID-19 患者的唾液中上调,3 种蛋白质在 COVID-19 患者的唾液中下调至少 5 倍。对蛋白质的分析表明,促炎和抗炎蛋白质之间存在着复杂的平衡关系,一些具有免疫活性的蛋白质数量减少,这可能有利于病毒的传播。这种减少可能与感染引起的内肽酶活性增强有关,而内肽酶活性增强反过来又改变了游离肽的平衡。事实上,在总共 28 种肽中,22 种(80%)在严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)和对照组中的表达不同。通过对这些肽进行多变量分析,可以获得一种诊断算法,以较高的诊断效率区分两种人群。在氨基酸中,只有苏氨酸在 COVID-19 患者和对照组之间存在显著差异,而丙氨酸水平在不同严重程度的 COVID-19 患者之间存在显著差异。总之,本研究确定了一组分子,可通过基于质谱串联的快速简便方法进行检测,从而揭示这种复杂疾病发病机制中的生化改变。数据可通过蛋白质组交换(ProteomeXchange)获得,标识符为 PXD045612。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Molecular fingerprint by omics-based approaches in saliva from patients affected by SARS-CoV-2 infection

Molecular fingerprint by omics-based approaches in saliva from patients affected by SARS-CoV-2 infection

Clinical expression of coronavirus disease 2019 (COVID-19) infectionis widely variable including fatal cases and patients with mild symptoms and a rapid resolution. We studied saliva from 63 hospitalized COVID-19 patients and from 30 healthy controls by integrating large-scale proteomics, peptidomics and targeted metabolomics to assess the biochemical alterations following the infection and to obtain a set of putative biomarkers useful for noninvasive diagnosis. We used an untargeted approach by using liquid chromatography–tandem mass spectrometry (LC–MS/MS) for proteomics and peptidomics analysis and targeted LC–multiple reaction monitoring/MS for the analysis of amino acids. The levels of 77 proteins were significantly different in COVID-19 patients. Among these, seven proteins were found only in saliva from patients with COVID-19, four were up-regulated and three were down-regulated at least five-folds in saliva from COVID-19 patients in comparison to controls. The analysis of proteins revealed a complex balance between pro-inflammatory and anti-inflammatory proteins and a reduced amount of several proteins with immune activity that possibly favours the spreading of the virus. Such reduction could be related to the enhanced activity of endopeptidases induced by the infection that in turn caused an altered balance of free peptides. In fact, on a total of 28 peptides, 22 (80%) were differently expressed in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and control subjects. The multivariate analysis of such peptides permits to obtain a diagnostic algorithm that discriminate the two populations with a high diagnostic efficiency. Among amino acids, only threonine resulted significantly different between COVID-19 patients and controls, while alanine levels were significantly different between COVID-19 patients with different severity. In conclusion, the present study defined a set of molecules to be detected with a quick and easy method based on mass spectrometry tandem useful to reveal biochemical alterations involved in the pathogenesis of such a complex disease. Data are available via ProteomeXchange with identifier PXD045612.

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来源期刊
Journal of Mass Spectrometry
Journal of Mass Spectrometry 化学-光谱学
CiteScore
5.10
自引率
0.00%
发文量
84
审稿时长
1.5 months
期刊介绍: The Journal of Mass Spectrometry publishes papers on a broad range of topics of interest to scientists working in both fundamental and applied areas involving the study of gaseous ions. The aim of JMS is to serve the scientific community with information provided and arranged to help senior investigators to better stay abreast of new discoveries and studies in their own field, to make them aware of events and developments in associated fields, and to provide students and newcomers the basic tools with which to learn fundamental and applied aspects of mass spectrometry.
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