Decoding neuroproteomics: integrating the genome, translatome and functional anatomy

Abstract

The immense inter- and intra-cellular heterogeneity of the central nervous system (CNS) presents major challenges for high-throughput *omic analyses. Transcriptional, translational, and post-translational regulatory events are localised to specific neuronal cell-types, or sub-cellular compartments, resulting in discrete patterns of protein expression and activity. A spatial and quantitative knowledge of the “neuroproteome” is therefore critical to understanding normal and pathological aspects of functional genomics and anatomy of the CNS. Improvements in mass-spectrometry allow profiling of proteins at sufficient depth to complement results from high-throughput genomic and transcriptomic assays. However, there are challenges in integrating proteomic data with other data modalities and even greater challenges obtaining comprehensive neuroproteomic data with cell-type specificity. Here we discuss how proteomics should be exploited to enhance high-throughput functional genomic analysis by tighter integration of data analyses. We also discuss experimental strategies to achieve finer cellular and sub-cellular resolution in transcriptomic and proteomic studies of neural tissues.

Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence

“…Additional technical advances are necessary to deploy the combination of such methods to study locally intermingled astrocytes. Our data showing that RNA and protein levels are not necessarily directly correlated in all cases echoes previous work (Kitchen et al, 2014) and provides an impetus to assess local diversity with multiple approaches.…”

“…Ideally, RNA and protein expression should be assessed in parallel (Kitchen et al, 2014). We documented the proteomes of purified striatal and hippocampal astrocytes from P30 Aldh1l1 -eGFP mice (Cahoy et al, 2008; Foo, 2013).…”

Spatiotemporal 16p11.2 Protein Network Implicates Cortical Late Mid-Fetal Brain Development and KCTD13-Cul3-RhoA Pathway in Psychiatric Diseases

“…This lack of resolution is largely due to the absence of the single-cell developmental transcriptome data that will ultimately be required to fully exploit novel approaches developed here. Further advancement of the single-cell genomic, transcriptomic and proteomic technologies (Shapiro et al, 2013), especially in the context of brain development (Kitchen et al, 2014), will open new avenues for improving the resolution of the dynamic spatio-temporal neuronal networks.…”

Neuroproteomics — LC-MS Quantitative Approaches

“…CNS is very complex, presenting a high degree of heterogeneity at several levels, such as distinct brain regions, cellular networks, and cell types [1], each one characterized by a different proteome. Even slight perturbations of this structure can lead to CNS disorders, resulting in alterations in the proteome of all CNS constituents or of specific cellular networks.…”