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Decoding neuroproteomics: integrating the genome, translatome and functional anatomy

Nature Neuroscience volume 17, pages 1491–1499 (2014)Cite this article

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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.

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Figure 1: Integrated genomic, transcriptomic and proteomic analyses and the central dogma.

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Acknowledgements

This work was supported by US National Institutes of Health grants DA018343 (A.C.N. and M.B.G.) and DA10044 (A.C.N.) and Department of the Army grant W81XWH-09-1-0434 (A.C.N.). Support was also obtained from the State of Connecticut, Department of Mental Health and Addiction Services.

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  1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA

    Robert R Kitchen, Joel S Rozowsky & Mark B Gerstein

  2. Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut, USA

    Robert R Kitchen & Angus C Nairn

  3. Program in Computational Biology, Yale University, New Haven, Connecticut, USA

    Joel S Rozowsky & Mark B Gerstein

  4. Department of Computer Science, Yale University, New Haven, Connecticut, USA

    Mark B Gerstein

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Kitchen, R., Rozowsky, J., Gerstein, M. et al. Decoding neuroproteomics: integrating the genome, translatome and functional anatomy. Nat Neurosci 17, 1491–1499 (2014). https://doi.org/10.1038/nn.3829

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