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原发性干燥综合征患者外周血单个核细胞的蛋白质组和磷酸化蛋白质组综合分析。

Integrated proteome and phosphoproteome analyses of peripheral blood mononuclear cells in primary Sjögren syndrome patients.

机构信息

Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital, The First Affiliated Hospital Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong, China.

Department of Rheumatology and Immunology, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong, China.

出版信息

Aging (Albany NY). 2020 Dec 3;13(1):1071-1095. doi: 10.18632/aging.202233.

Abstract

Primary Sjögren syndrome (pSS) is a common autoimmune disease. Here, we performed the first proteome and phosphoproteome analyses of peripheral blood mononuclear cells in pSS patients to obtain a comprehensive profile and identify the potential crucial proteins and pathways for the screening and evaluation of pSS patients. Peripheral blood mononuclear cells from 8 pSS-confirmed patients (American-European Consensus Group Criteria, 2002) and 10 normal controls were selected. Label-free quantitative proteomics was utilized to obtain quantitative information. In total, 787 proteins were identified as differentially expressed proteins, and 175 phosphosites on 123 proteins were identified as differentially phosphorylated proteins. We performed functional enrichment analyses with these proteins and phosphoproteins based on public database. Furthermore, protein-protein interaction network analyses were performed by using multiple algorithms. Using module and hub protein analyses, we identified 16 modules for the proteins, 2 clusters for the phosphoproteins and selected the top 10 hub proteins. Finally, we identified 22 motifs using motif analysis of the phosphosites and found 17 newly identified motifs, while 6 motifs were experimentally verified for known protein kinases. The findings distinguished pSS patients from normal controls at the peripheral blood mononuclear cells level and revealed potential candidates for use in pSS diagnosis.

摘要

原发性干燥综合征(pSS)是一种常见的自身免疫性疾病。在这里,我们对 pSS 患者的外周血单个核细胞进行了首次蛋白质组和磷酸化蛋白质组分析,以获得全面的图谱,并确定筛选和评估 pSS 患者的潜在关键蛋白质和途径。选择了 8 名 pSS 确诊患者(2002 年美国-欧洲共识组标准)和 10 名正常对照者的外周血单个核细胞。采用无标记定量蛋白质组学获得定量信息。共鉴定出 787 种差异表达蛋白,鉴定出 123 种蛋白上的 175 个磷酸化位点为差异磷酸化蛋白。我们基于公共数据库对这些蛋白质和磷酸化蛋白质进行了功能富集分析。此外,还使用多种算法进行了蛋白质-蛋白质相互作用网络分析。通过模块和枢纽蛋白分析,我们鉴定了 16 个蛋白质模块,2 个磷酸化蛋白质簇,并选择了前 10 个枢纽蛋白。最后,我们通过对磷酸化位点的motif 分析发现了 22 个motif,并找到了 17 个新的鉴定出的 motif,而 6 个 motif 已被实验验证为已知蛋白激酶。这些发现将 pSS 患者与外周血单个核细胞水平的正常对照者区分开来,并揭示了用于 pSS 诊断的潜在候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4775/7835054/e691d13312fa/aging-13-202233-g001.jpg

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