A multiregional proteomic survey of the postnatal human brain

Abstract

Detailed observations of transcriptional, translational, and post-translational events in the human brain are essential to improving our understanding of its development, function, and vulnerability to disease. Here, we exploited label-free quantitative tandem mass-spectrometry proteomics to create an in-depth proteomic survey of adult human brain regions. Integration of protein data with existing whole-transcriptome sequencing (RNA-seq) from the BrainSpan project revealed varied patterns of protein:RNA relationships with generally increased magnitudes of protein abundance differences between brain regions compared to RNA. Many of the differences amplified in protein data were reflective of cyto-architectural and functional variation between brain regions. Comparing structurally similar cortical regions revealed significant differences in the abundance of receptor-associated and resident plasma membrane proteins that were not readily observed in the RNA expression data.

Adenosine‐to‐Inosine RNA Editing in Mouse and Human Brain Proteomes

“…In order to identify edited sites in the human brain proteome, we used the same study design as for murine data. Similarly, there was a main dataset that yielded the majority of identified edited peptides . Even the authors of the original paper by Carlyle et al stated that their work was a human analogue of the major murine study by Sharma et al .…”

“…The sites with two or more spectral counts are listed in the top of the table, and those with a single spectrum detected are in the bottom. All but two sites shown are found in the deep brain proteome by Carlyle et al . The values in the right column are summarized peptide spectral counts of each edited site in all samples analyzed there, unless otherwise specified.…”

“…One more dataset, obtained in the proteogenomic study of prefrontal cortex, was not deep enough and yielded thirteen edited sites as a subset of deepest human dataset except a single unique site from the polymerase delta‐interacting protein 3 (Table ). Even the deepest human dataset obtained by Carlyle et al .…”

“…Some journals in the field, even well‐established, do not oblige contributors to provide raw proteome data. There were two major datasets available for murine and human brain, PXD001250 and PXD005445, respectively. These latter were specifically directed to the inventory of brain proteomes and, to the authors’ knowledge, represented the deepest brain proteomes available to date.…”

Widespread Accumulation of Ribosome-Associated Isolated 3′ UTRs in Neuronal Cell Populations of the Aging Brain

“…To explore the possibility that peptides are produced from ribosomes associated with isolated 3′ UTRs in mammals, we analyzed tandem mass-spectrometry (MS/MS) data derived from post-mortem human brain surveyed across 7 different tissues (Carlyle et al, 2017). Spectra were mapped to both the UniProt protein database as well as a custom database of translated 3′ UTR ORFs (STAR Methods).…”