基于网络的单核细胞膜亚细胞蛋白质组学揭示了骨质疏松症相关的新候选基因。
Network based subcellular proteomics in monocyte membrane revealed novel candidate genes involved in osteoporosis.
机构信息
College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China.
Center of Bioinformatics and Genomics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA.
出版信息
Osteoporos Int. 2017 Oct;28(10):3033-3042. doi: 10.1007/s00198-017-4146-5. Epub 2017 Jul 24.
UNLABELLED
In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels.
INTRODUCTION
Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis.
METHODS
To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools.
RESULTS
A total of 1070 membrane proteins were identified and quantified. By comparing the proteins' expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB (p = 0.0021), CD36 (p = 0.0104), ACTN1 (p = 0.0381), and ITGB1 (p = 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including "ECM-receptor interaction," "calcium ion binding," "leukocyte transendothelial migration," and "reduction of cytosolic calcium levels." Results from transcriptomic and genomic levels provided additional supporting evidences.
CONCLUSION
Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.
未加标签
在这项研究中，基于无标签的定量亚细胞蛋白质组学与网络分析相结合，突出了几个候选基因，包括 P4HB、ITGB1、CD36 和 ACTN1，它们可能与骨质疏松症有关。所有这些基因都被预测为具有高置信度的重要膜蛋白，并富含与骨骼相关的生物学过程。这些结果在转录组和基因组水平上得到了进一步验证。
引言
骨质疏松症是一种代谢性骨病，主要特征是骨矿物质密度（BMD）低。外周血单核细胞（PBMs）作为破骨细胞的前体，被认为是鉴定与骨质疏松症相关基因的重要候选者。我们进行了亚细胞蛋白质组学研究，以鉴定参与骨质疏松症的重要膜蛋白。
方法
为了研究单核细胞、膜蛋白与骨质疏松症之间的关系，我们对 59 名男性受试者进行了无标签定量亚细胞蛋白质组学研究，其中 30 名受试者的 BMD 较高，29 名受试者的 BMD 较低。随后，我们基于多个生物信息学工具进行了综合基因富集分析、功能注释、途径和网络分析。
结果
共鉴定和定量了 1070 种膜蛋白。通过比较蛋白质表达水平，我们发现高 BMD 组和低 BMD 组之间有 36 种蛋白表达存在差异。蛋白质定位预测支持以下观点，即差异表达蛋白 P4HB（p=0.0021）、CD36（p=0.0104）、ACTN1（p=0.0381）和 ITGB1（p=0.0385）是重要的膜蛋白。功能注释和途径及网络分析强调，P4HB、ITGB1、CD36 和 ACTN1 富集在与骨质疏松症相关的途径和术语中，包括“ECM-受体相互作用”、“钙离子结合”、“白细胞穿过内皮迁移”和“细胞内钙离子水平降低”。转录组和基因组水平的结果提供了额外的支持证据。
结论
我们的研究强烈支持 P4HB、ITGB1、CD36 和 ACTN1 基因对骨质疏松症风险病因的重要性。
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