In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling.

In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling.
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DOI:
10.3390/proteomes9010006
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发表时间:
2021-01-29
期刊:
影响因子:
3.3
通讯作者:
Hanson MR
Hanson MR
中科院分区:
其他
文献类型:
--
作者:
Germain A;Levine SM;Hanson MR

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肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种致残性疾病,在全球范围内普遍存在,仅针对症状治疗的治疗方法有限。为了深入了解ME/CFS中的分子破坏,我们利用了一种基于适体的技术,该技术量化了4790种独特的人类蛋白质,使我们能够获得迄今为止可用于这种疾病的最大蛋白质组学数据集,检测高度丰富的蛋白质以及超过9个对数动态范围的稀有蛋白质。我们报告了一项试点研究20 ME/CFS患者和20名对照,所有女性。组群之间19种蛋白质水平的显著差异暗示了与细胞外基质、免疫系统和细胞间通讯相关的途径。通路和聚类分析的结果有力地突出了肝配蛋白通路,其参与细胞-细胞信号传导和多种生物过程的调节,包括轴突导向、血管生成、上皮细胞迁移和免疫应答。受试者操作特征(ROC)曲线分析以高准确度(曲线下面积(AUC)> 0.85)将ME/CFS患者的血浆蛋白质组与对照区分开,并且当使用蛋白质比率(AUC高达0.95)时甚至更高,所述蛋白质比率包括具有确定的生物学相关性的一些蛋白质对。我们的研究结果说明了血浆蛋白质组学诊断和破译ME/CFS的分子基础的承诺。
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease with worldwide prevalence and limited therapies exclusively aimed at treating symptoms. To gain insights into the molecular disruptions in ME/CFS, we utilized an aptamer-based technology that quantified 4790 unique human proteins, allowing us to obtain the largest proteomics dataset yet available for this disease, detecting highly abundant proteins as well as rare proteins over a nine-log dynamic range. We report a pilot study of 20 ME/CFS patients and 20 controls, all females. Significant differences in the levels of 19 proteins between cohorts implicate pathways related to the extracellular matrix, the immune system and cell–cell communication. Outputs of pathway and cluster analyses robustly highlight the ephrin pathway, which is involved in cell–cell signaling and regulation of an expansive variety of biological processes, including axon guidance, angiogenesis, epithelial cell migration, and immune response. Receiver Operating Characteristic (ROC) curve analyses distinguish the plasma proteomes of ME/CFS patients from controls with a high degree of accuracy (Area Under the Curve (AUC) > 0.85), and even higher when using protein ratios (AUC up to 0.95), that include some protein pairs with established biological relevance. Our results illustrate the promise of plasma proteomics for diagnosing and deciphering the molecular basis of ME/CFS.
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