Decoding neuroproteomics: integrating the genome, translatome and functional anatomy.

Abstract

The immense intercellular and intracellular heterogeneity of the CNS presents major challenges for high-throughput omic analyses. Transcriptional, translational and post-translational regulatory events are localized to specific neuronal cell types or subcellular compartments, resulting in discrete patterns of protein expression and activity. A spatial and quantitative knowledge of the neuroproteome is therefore critical to understanding both normal and pathological aspects of the functional genomics and anatomy of the CNS. Improvements in mass spectrometry allow the profiling of proteins at a 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 in 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 subcellular resolution in transcriptomic and proteomic studies of neural tissues.