人血浆蛋白质组的昼夜节律。

IF 3.3 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Elvar M S Jóhönnuson, Henriette P Sennels, Henrik L Jørgensen, Jens Hannibal, Ching-Yan Chloé Yeung, Christine Rasmussen, Gabriela Zofia Prus, Nicolai J Wewer Albrechtsen, Annelaura Bach Nielsen
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引用次数: 0

摘要

背景:血浆是最常用的临床标本,但血浆蛋白的日变化在很大程度上仍未被探索。我们旨在确定健康个体的昼夜调节蛋白,评估其潜在的诊断意义,并强调昼夜意识如何推进未来的生物标志物研究。方法:在高度控制的条件下,对24名健康青年进行研究。24小时内每隔3小时抽取一次静脉血,共采集216份样本,其中208份高质量血浆样本通过高通量质谱分析。对缺失数据进行过滤和输入,并使用基于余弦校正的benjamin - hochberg校正模型评估节律性。使用DAVID功能注释工具进行组织和途径富集分析。结果:在523个通过质量阈值的蛋白质中,138个(约26%)表现出显著的日振荡。组织富集分析显示,大多数节律性蛋白起源于肝脏和血小板,在各种组织类型中有额外的富集。途径富集显示了止血、免疫信号、整合素介导的过程、葡萄糖代谢和蛋白质合成的昼夜调节。值得注意的是,包括白蛋白、淀粉酶和胱抑素C在内的36种临床使用的生物标志物显示出日变化,这表明不考虑时间波动可能会降低诊断的准确性。解释:这些发现表明,超过四分之一的人类血浆蛋白质组处于昼夜控制之下。这种振荡可能有直接的临床意义,因为一天中的时间可能会改变生物标志物的准确性。通过标准化采样或时间敏感参考间隔,将昼夜计时纳入诊断和研究方案,可以改善患者护理,并为未来的生物标志物发现提供信息。需要在更大、更多样化的人群中进行进一步的研究,以推广这些结果,并以一种考虑到日变化的方式简化实践。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Diurnal rhythm of the human plasma proteome.

Background: Plasma is the most used clinical specimen, yet diurnal variation in plasma proteins remains largely unexplored. We aimed to identify diurnally-regulated proteins in healthy individuals and assess their potential diagnostic implications, and highlight how diurnal awareness can advance future biomarker research.

Methods: Twenty-four healthy young individuals were studied under highly controlled conditions. Venous blood was drawn every three hours over a 24-h period, yielding 216 samples, of which 208 high-quality plasma samples were analyzed via high-throughput mass spectrometry. The missing data were filtered and imputed, and rhythmicity was assessed using Cosinor-based modeling with Benjamini-Hochberg correction. Tissue and pathway enrichment analyses were performed using the DAVID functional annotation tool.

Findings: Of 523 proteins that passed quality thresholds, 138 (~ 26%) exhibited significant diurnal oscillations. Tissue enrichment analysis revealed that most rhythmic proteins originated from the liver and platelets, with additional enrichment in a variety of tissue types. Pathway enrichment showed diurnal regulation of hemostasis, immune signaling, integrin-mediated processes, glucose metabolism, and protein synthesis. Notably, 36 clinically utilized biomarkers, including albumin, amylase, and cystatin C exhibited diurnal variation, suggesting that failing to account for temporal fluctuations may reduce diagnostic precision.

Interpretation: These findings demonstrate that over one-quarter of the human plasma proteome is under diurnal control. Such oscillations might have direct clinical implications, as the time-of-day may alter biomarker accuracy. Incorporating diurnal timing into diagnostic and research protocols, through standardized sampling or time-sensitive reference intervals, could improve patient care and inform future biomarker discoveries. Further research in larger, more diverse populations is needed to generalize these results and streamline practices in a way that takes diurnal variation into account.

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来源期刊
Clinical proteomics
Clinical proteomics BIOCHEMICAL RESEARCH METHODS-
CiteScore
5.80
自引率
2.60%
发文量
37
审稿时长
17 weeks
期刊介绍: Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.
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