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

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 in silico 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.

本研究针对左右大脑半球的19个脑区开展了大规模质谱分析，首次绘制了人类大脑半球间蛋白质组（interhemispheric proteome）的首张草图。本研究获取的高分辨率蛋白质组数据对多个脑区的3300种经实验验证（非假设性）蛋白质实现了全面覆盖，可用于解析以蛋白质为核心的半球间差异与突触生物学特征，同时可为脑疾病生物标志物的特定脑区定位绘制区域图谱。在人类蛋白质组计划（Human Proteome Project, HPP）的框架下，本研究的半球间蛋白质组数据揭示了一批特异性标志物：小脑蚓部中的嵌合蛋白2（chimerin 2, CHN2）、嗅球中的嗅觉标记蛋白（olfactory marker protein, OMP）以及基底神经节中的锚蛋白重复结构域63（ankyrin repeat domain 63, ANKRD63），该结果与人类蛋白质图谱（Human Protein Atlas, HPA）中绘制的脑区转录组数据相一致。此外，本研究通过计算机分析流程，对未被注释的uPE1蛋白质ANKRD63的结构与功能进行了预测，并通过平行反应监测（parallel reaction monitoring, PRM）技术验证了其脑区特异性表达模式。最后，本研究搭建了大脑半球间蛋白质组图谱（Interhemispheric Brain Proteome Map, IBPM）门户网站（www.brainprot.org），以期激发科学界对大脑分子图谱的研究兴趣，推动并助力神经蛋白质组学领域的相关研究。本研究数据可通过ProteomeXchange数据库获取，登录号为PXD019936。