Zamanian Azodi Mona, Arjmand Babak, Zali Alireza, Razzaghi Mohammadreza
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Gastroenterol Hepatol Bed Bench. 2020 Fall;13(4):367-373.
Introducing possible diagnostic and therapeutic biomarker candidates via the identification of chief dysregulated proteins in COVID-19 patients is the aim of this study.
Molecular studies, especially proteomics, can be considered as suitable approaches for discovering the hidden aspect of the disease.
Differentially expressed proteins (DEPs) of three patients with demonstrated severe condition (S-COVID-19) were compared to healthy cases by a proteomics study. Cytoscape software and STRING database were used to construct the protein-protein interaction (PPI) network. The central DEPs were identified through topological analysis of the network. ClueGO+CluePedia were applied to find the biological processes related to the central nodes. MCODE molecular complex detection (MCODE) was used to discover protein complexes.
A total of 242 DEPs from among 256 query ones were included in the network. Centrality analysis of the network assigned 16 hub-bottlenecks, nine of which were presented in the highest-scored protein complex. Ten protein complexes were determined. APOA1 was identified as the protein complex seed, and APP, EGF, and C3 were the top hub-bottlenecks of the network. The results specify that up-regulation of C3 and down-regulation of APOA1 in urine play a role in the stiffness in respiration and, accordingly, the severity of COVID-19. Moreover, dysregulation of APP and APOA1 could both contribute to the possible adverse effects of COVID-19 on the nervous system.
The introduced central proteins of the S-COVID-19 interaction network, particularly APOA1, can be considered as diagnostic and therapeutic targets related to the coronavirus disease after being approved with complementary studies.
通过识别新冠肺炎患者主要失调的蛋白质来引入可能的诊断和治疗生物标志物候选物是本研究的目的。
分子研究,尤其是蛋白质组学,可被视为发现疾病隐藏方面的合适方法。
通过蛋白质组学研究,将三名确诊为重症的患者(S-COVID-19)的差异表达蛋白(DEP)与健康病例进行比较。使用Cytoscape软件和STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络。通过网络的拓扑分析确定核心DEP。应用ClueGO+CluePedia查找与核心节点相关的生物学过程。使用MCODE分子复合物检测(MCODE)发现蛋白质复合物。
网络中纳入了256个查询蛋白中的242个DEP。网络的中心性分析确定了16个枢纽瓶颈蛋白,其中9个出现在得分最高的蛋白质复合物中。确定了10个蛋白质复合物。APOA1被确定为蛋白质复合物种子,APP、EGF和C3是网络的顶级枢纽瓶颈蛋白。结果表明,尿液中C3的上调和APOA1的下调在呼吸僵硬中起作用,进而与COVID-19的严重程度相关。此外,APP和APOA1的失调都可能导致COVID-19对神经系统的潜在不良影响。
S-COVID-19相互作用网络中引入的核心蛋白,特别是APOA1,经补充研究验证后,可被视为与冠状病毒病相关的诊断和治疗靶点。