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全面分析人类正常羊水蛋白质组的图谱和个体间差异。

A comprehensive profile and inter-individual variations analysis of the human normal amniotic fluid proteome.

机构信息

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

J Proteomics. 2019 Feb 10;192:1-9. doi: 10.1016/j.jprot.2018.04.023. Epub 2018 Apr 22.

DOI:10.1016/j.jprot.2018.04.023
PMID:29684686
Abstract

Amniotic fluid contains large amounts of proteins produced by amnion epithelial cells, fetal tissues, fetal excretions and placental tissues; thus, it is an important potential source of biomarkers for identifying fetal pathologies. In this study, a pooled AF sample from 7 healthy volunteers was used to provide a comprehensive profile of normal human AF proteome using immunoaffinity depletion of 14 high-abundance proteins. Each individual AF sample was used to analyze inter-individual variations with iTRAQ method. As a result, a total of 2881 non-redundant proteins were identified, and 1624 proteins were quantified based on the peak intensity-based semi-quantification (iBAQ) method. Gene Ontology (GO) analysis showed that the AF proteome was enriched in extracellular region and extracellular matrix. Further function annotation showed that the top canonical pathway was axonal guidance signaling. The inter-individual variation analysis of 7 individual AF samples showed that the median inter-individual CV (Coefficient of variation) was 0.22. iBAQ quantification analysis revealed that the inter-individual variations were not correlated with protein abundance. GO analysis indicated that intracellular proteins tended to have higher CVs, and extracellular proteins tended to have lower CVs. These data will contribute to a better understanding of amniotic fluid proteomic analysis and biomarker discovery. SIGNIFICANCE: Amniotic fluid is an important potential source of biomarkers for identifying fetal pathologies. This study provided a large database for the normal human amniotic fluid proteome and analysis of inter-individual variations in amniotic fluid proteomes, which will offer a baseline reference for further AF proteomic analysis and pregnancy-related disease biomarker discovery.

摘要

羊水含有大量由羊膜上皮细胞、胎儿组织、胎儿排泄物和胎盘组织产生的蛋白质;因此,它是识别胎儿病理的潜在生物标志物的重要来源。在这项研究中,使用来自 7 名健康志愿者的混合羊水样本,通过免疫亲和去除 14 种高丰度蛋白质,提供正常人类羊水蛋白质组的全面概况。使用 iTRAQ 方法分析每个个体羊水样本的个体间差异。结果共鉴定出 2881 个非冗余蛋白质,根据基于峰强度的半定量(iBAQ)方法定量 1624 个蛋白质。基因本体论(GO)分析表明,羊水蛋白质组富含细胞外区和细胞外基质。进一步的功能注释表明,主要的经典途径是轴突导向信号。7 个个体羊水样本的个体间差异分析表明,中位数个体间变异系数(CV)为 0.22。iBAQ 定量分析表明,个体间差异与蛋白质丰度无关。GO 分析表明,细胞内蛋白质倾向于具有更高的 CVs,而细胞外蛋白质倾向于具有更低的 CVs。这些数据将有助于更好地理解羊水蛋白质组分析和生物标志物发现。意义:羊水是识别胎儿病理的潜在生物标志物的重要来源。本研究为正常人类羊水蛋白质组提供了一个大型数据库,并分析了羊水蛋白质组的个体间差异,这将为进一步的羊水蛋白质组分析和妊娠相关疾病生物标志物发现提供基线参考。

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