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解析人类蛋白质组计划背景下人脑的区域间和半球间蛋白质组。

Deciphering the Interregional and Interhemisphere Proteome of the Human Brain in the Context of the Human Proteome Project.

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Department of Mathematics, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

出版信息

J Proteome Res. 2021 Dec 3;20(12):5280-5293. doi: 10.1021/acs.jproteome.1c00511. Epub 2021 Oct 29.

DOI:10.1021/acs.jproteome.1c00511
PMID:34714085
Abstract

This study, which performs an extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres, presents the first draft of the human brain interhemispheric proteome. This high-resolution proteomics data provides comprehensive coverage of 3300 experimentally measured (nonhypothetical) proteins across multiple regions, allowing the characterization of protein-centric interhemispheric differences and synapse biology, and portrays the regional mapping of specific regions for brain disorder biomarkers. In the context of the Human Proteome Project (HPP), the interhemispheric proteome data reveal specific markers like chimerin 2 (CHN2) in the cerebellar vermis, olfactory marker protein (OMP) in the olfactory bulb, and ankyrin repeat domain 63 (ANKRD63) in basal ganglia, in line with regional brain transcriptomes mapped in the Human Protein Atlas (HPA). In addition, an analysis pipeline was used to predict the structure and function of the uncharacterized uPE1 protein ANKRD63, and parallel reaction monitoring (PRM) was applied to validate its region-specific expression. Finally, we have built the Interhemispheric Brain Proteome Map (IBPM) Portal (www.brainprot.org) to stimulate the scientific community's interest in the brain molecular landscape and accelerate and support research in neuroproteomics. Data are available via ProteomeXchange with identifier PXD019936.

摘要

这项研究对来自左右大脑半球的 19 个脑区进行了广泛的基于质谱的分析,提出了人类大脑半球间蛋白质组的初稿。这项高分辨率蛋白质组学数据全面涵盖了多个区域的 3300 种经过实验测量的(非假设的)蛋白质,允许对以蛋白质为中心的半球间差异和突触生物学进行特征描述,并描绘出特定区域的区域映射用于脑疾病生物标志物。在人类蛋白质组计划(HPP)的背景下,半球间蛋白质组数据揭示了小脑蚓部的嵌合体蛋白 2(CHN2)、嗅球的嗅觉标记蛋白(OMP)和基底神经节的锚蛋白重复域 63(ANKRD63)等特定标志物与人类蛋白质图谱(HPA)中映射的区域脑转录组一致。此外,还使用分析管道来预测未表征的 uPE1 蛋白 ANKRD63 的结构和功能,并应用平行反应监测(PRM)来验证其区域特异性表达。最后,我们构建了半球间脑蛋白质组图谱(IBPM)门户(www.brainprot.org),以激发科学界对大脑分子景观的兴趣,加速和支持神经蛋白质组学的研究。数据可通过 ProteomeXchange 以标识符 PXD019936 获得。

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