Lazari Lucas Cardoso, Ghilardi Fabio De Rose, Rosa-Fernandes Livia, Assis Diego M, Nicolau José Carlos, Santiago Veronica Feijoli, Dalçóquio Talia Falcão, Angeli Claudia B, Bertolin Adriadne Justi, Marinho Claudio Rf, Wrenger Carsten, Durigon Edison Luiz, Siciliano Rinaldo Focaccia, Palmisano Giuseppe
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Instituto de Medicina Tropical, University of São Paulo, São Paulo, Brazil.
Life Sci Alliance. 2021 Jun 24;4(8). doi: 10.26508/lsa.202000946. Print 2021 Aug.
SARS-CoV-2 infection poses a global health crisis. In parallel with the ongoing world effort to identify therapeutic solutions, there is a critical need for improvement in the prognosis of COVID-19. Here, we report plasma proteome fingerprinting that predict high (hospitalized) and low-risk (outpatients) cases of COVID-19 identified by a platform that combines machine learning with matrix-assisted laser desorption ionization mass spectrometry analysis. Sample preparation, MS, and data analysis parameters were optimized to achieve an overall accuracy of 92%, sensitivity of 93%, and specificity of 92% in dataset without feature selection. We identified two distinct regions in the MALDI-TOF profile belonging to the same proteoforms. A combination of SDS-PAGE and quantitative bottom-up proteomic analysis allowed the identification of intact and truncated forms of serum amyloid A-1 and A-2 proteins, both already described as biomarkers for viral infections in the acute phase. Unbiased discrimination of high- and low-risk COVID-19 patients using a technology that is currently in clinical use may have a prompt application in the noninvasive prognosis of COVID-19. Further validation will consolidate its clinical utility.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引发了一场全球健康危机。在全球致力于寻找治疗方案的同时,改善新型冠状病毒肺炎(COVID-19)的预后也迫在眉睫。在此,我们报告了血浆蛋白质组指纹图谱,该图谱可预测通过将机器学习与基质辅助激光解吸电离质谱分析相结合的平台识别出的COVID-19高风险(住院)和低风险(门诊)病例。对样品制备、质谱分析和数据分析参数进行了优化,在未进行特征选择的数据集上实现了92%的总体准确率、93%的灵敏度和92%的特异性。我们在基质辅助激光解吸电离飞行时间(MALDI-TOF)图谱中确定了属于同一蛋白质形式的两个不同区域。十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)和定量自下而上蛋白质组分析相结合,使得血清淀粉样蛋白A-1和A-2蛋白质的完整和截短形式得以鉴定,这两种蛋白质均已被描述为急性期病毒感染的生物标志物。使用目前临床应用中的技术对COVID-19高风险和低风险患者进行无偏倚区分,可能会在COVID-19的无创预后中迅速得到应用。进一步验证将巩固其临床实用性。