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

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 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 () 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.

Analysis of human brain tissue derived from DBS surgery

“…The datasets achieved by our method were compared to the datasets obtained using the BTI approach described by Zaccaria et al . [ 12 ] and postmortem samples from specific brain regions [ 31 , 32 ] (Fig. 4 a).…”

“…b The gene expression patterns of 13 proteins, that were identified by Biswas et al . [ 32 ] to be differentially expressed in the basal ganglia between the left and right hemispheres, also clustered according to hemisphere in the clustering analysis based on our RNA-seq data. We tested the top 20% expressed RNA-seq identifiers common to all analyzed samples ( n = 1980) using the SynGO Knowledge base gene set enrichment tool [ 33 ].…”

“…Biswas et al . studied, for the first time, brain hemisphere-specific proteome in several brain anatomical regions [ 32 ] from one individual and they identified 13 differentially expressed proteins between right and left basal ganglia. Interestingly, when we did the clustering analysis based on the RNA-seq data of these 13 genes identified by Biswas et al ., our samples also clustered according to hemisphere (Fig.…”

“…The brain region- and hemisphere-specific postmortem datasets were from the publication by Biswas et al . [ 32 ]. For enrichment analysis, a proteomics dataset that included proteins expressed in the frontal cortex and the frontal white matter was generated.…”

“…To study clustering of the RNA-seq samples according to specific transcripts, the list of the 13 proteins (FKBP4, GMFB, GNB2, HNRNPA1, HSPA6, PA2G4, PEA15, PYGM, SDHA, SELENBP1, SLC9A3R1, SNX3 and UBA52) found to be differentially expressed in the basal ganglia regions were picked from the publication by Biswas et al . [ 32 ]. For the hierarchical clustering and expression heatmap, transcription of each target gene per million expression levels was analyzed.…”