Deep Phosphoproteome Landscape of Interhemispheric Functionality of Neuroanatomical Regions of the Human Brain.

Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack of proteome-level knowledge of hemispheric lateralization. We have investigated the proteome level expression in different neuroanatomical regions under the Human Brain Proteome Project (HBPP) and developed the global interhemispheric brain proteome map (Brainprot) earlier. Furthermore, this study has extended to decipher the phosphoproteome map of human brain interhemispheric regions through high-resolution mass spectrometry. The phosphoproteomics examination of 12 unique interhemispheric neurological brain regions using Orbitrap fusion liquid chromatography with tandem mass spectrometry provided comprehensive coverage of 996 phosphoproteins, 2010 phosphopeptides, and 3567 phosphosites. Moreover, interhemispheric phosphoproteome profiling has been categorized according to synaptic ontologies and interhemispheric expression to understand the functionality. Finally, we have integrated the phosphosites data under the PhosphoMap section in the Inter-Hemispheric Brain Proteome Map Portal (https://www.brainprot.org/) for the advancement and support of the ongoing neuroproteomics research worldwide. Data is available via ProteomeXchange with the identifier PXD031188.

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.