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Cited by 63Advanced Proteomics Techniques and ApplicationsBioinformatics and Genomic NetworksSingle-cell and spatial transcriptomics

Decoding neuroproteomics: integrating the genome, translatome and functional anatomy

Open access
Kitchen, Robert R, Rozowsky, Joel S, Gerstein, Mark B, Nairn, Angus C·2014·Nature Neuroscience
DOI 10.1038/nn.3829PMC PMC4737617
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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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Crossref · 10.1038/nn.3829

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  • Premisereasoning

    None of these methods provide quantitative measurement of abundances or the state of activity of molecules within specific cell types of the CNS.

    “Importantly, none of these methods provide quantitative measurement of abundances or the state of activity of molecules within specific cell types of the CNS.”
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  • Premisecitation

    Increased subcellular resolution combined with mass-spectrometry can improve dynamic range and sensitivity to low-abundance or membrane-specific proteins that would otherwise be occluded by highly abundant nuclear and cytosolic proteins.

    “Increased sub-cellular resolution combined with mass-spectrometry can improve the dynamic range and sensitivity to low abundance or membrane-specific proteins that may otherwise be occluded by highly abundant nuclear and cytosolic proteins32.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    RNA expression studies across the mammalian brain have shown significant differences in the transcriptome between neuronal cell types, brain regions, developmental stages, and species.

    “Each have reinforced findings of significant differences in the transcriptome between neuronal cell-types, brain regions, developmental stages, and species.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
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  • Premisecitation

    Mass-spectrometry remains the only method of profiling the neuroproteome with throughput and resolving power comparable to other functional genomic methods.

    “Mass-spectrometry remains the only method of profiling the neuroproteome with a throughput and resolving power comparable to other functional genomic methods25.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Mass-spectrometry has proven valuable for locating PTMs implicated in CNS development and disorder, including p300-mediated acetylation of Tau and phosphorylation regulation of LSD1.

    “For example, mass spectrometry has proven to be a valuable tool for locating PTMs implicated in CNS development37 and disorder38, including interrogating specific hypotheses such as the p300-mediated acetylation of Tau39 and the regulation of the transcriptional repressor LSD1 through phosphorylation40.”
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    Premisereasoning

    Mass-spectrometry directly obtains PTM information due to characteristic mass shifts, providing exact locations and relative abundance measurements.

    “This information is obtained directly by mass-spectrometry due to the characteristic mass-shift that these modifications cause in the peptide spectra and, as such, provides not only the exact locations of these modifications but also measurements of their relative abundance.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Tandem mass-spectrometry is the most popular technology for protein-level analyses, enabling unbiased identification and quantification across the entire proteome.

    “Tandem mass-spectrometry is the most popular technology for protein-level analyses, enabling unbiased identification and quantification across the entire proteome19.”
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    Premisecitation

    Proteomic profiling of the nucleus has enabled simultaneous quantification of expressed transcription factors and identification of novel regulatory proteins.

    “Further, proteomic profiling of the nucleus has enabled simultaneous quantification of the complete set of expressed transcription factors and has been vital in identifying novel regulatory proteins42.”
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    Mass-spectrometry has become flexible due to targeted analysis of selected peptides or proteins and chemical labelling for greater quantification accuracy.

    “Mass-spectrometry has become very flexible, thanks to options for targeted analysis of selected peptides or proteins20 and methods for chemically labelling samples to obtain greater protein quantification accuracy21.”
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    Premisenone given

    Mass-spectrometry proteomics primarily provides sequences, PTMs, and abundances of up to tens of thousands of peptides and/or proteins in a sample.

    “The primary insights offered by mass-spectrometry proteomics are the sequences, post-translational modifications (PTMs), and abundances of up to tens of thousands of peptides and/or proteins in a given sample.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    The central nervous system is highly heterogeneous across and within cells, and transcriptional, translational, and post-translational regulatory events occur in specific neuronal cell types or subcellular compartments, producing discrete protein expression and activity patterns.

    “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.”
    Quote in the paperSubstantial claim0 of 3 sources checked
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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Integrating proteomic data with other data modalities is challenging, and obtaining comprehensive neuroproteomic data with cell-type specificity is even more challenging.

    “However, there are challenges in integrating proteomic data with other data modalities and even greater challenges obtaining comprehensive neuroproteomic data with cell-type specificity.”
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    Premisenone given

    Such atlases are limited in throughput and information regarding cell types.

    “Such atlases, while extremely important, are limited in throughput and information regarding cell types.”
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    Premisecitation

    It is now possible to reliably obtain quantitative observations for tens of thousands of peptides derived from up to 10,000 proteins per sample, and steps have been taken toward profiling the entire human proteome.

    “Despite this limitation, it is now possible to reliably obtain quantitative observations for tens of thousands of peptides derived from up to 10,000 proteins per sample22, and very recently important steps have been taken toward profiling the entire human proteome23,24.”
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    Premisenone given

    Mass-spectrometry improvements now permit protein profiling at sufficient depth to complement high-throughput genomic and transcriptomic assays.

    “Improvements in mass-spectrometry allow profiling of proteins at sufficient depth to complement results from high-throughput genomic and transcriptomic assays.”
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    Premisecitation

    PTMs such as acetylation, acylation, deamidation, glycosylation, methylation, and ubiquitination play pivotal roles in regulating almost all cellular processes.

    “In addition to phosphorylation, PTMs such as acetylation, acylation, deamidation, glycosylation, methylation, and ubiquitination play pivotal roles in regulating almost all cellular processes including energy production and transport, DNA modification, transcription and translation of RNA, and RNA or protein stability36.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Metabolic labelling of amenable cells can yield insight into protein turnover rates and has revealed that proteins are more abundant and have longer half-life than RNAs.

    “Extending beyond comparison of steady state protein expression, metabolic labelling of amenable cells (for example in culture) is capable of yielding valuable insight to the rates of protein turnover and has revealed that proteins are both more abundant and have a longer half-life than do RNAs33.”
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    • cites [33] Schwanhäusser, B. et al. Global quantification of mammalian gene expression control. Nature 473, 337–342 (2011). source

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    A recent survey of mouse CNS revealed 1,300 ASE transcripts favouring maternal allele during brain development, while in adult the bias shifts toward paternal allele.

    “A recent survey of the mouse CNS revealed 1,300 ASE transcripts that favour the maternal allele during brain development, while in the adult the bias shifts toward the paternal allele85.”
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    RNA-editing (RDDs) appears to have played a significant role in human brain evolution, and ADAR3 is exclusively expressed in the brain.

    “RNA-editing, also referred to as RNA-DNA differences (RDDs), appears to have played a significant role in human brain evolution16,77 and of the trio of ADAR proteins responsible for the post-transcriptional A-to-I modification, ADAR3 is exclusively expressed in the brain16.”
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    Premisecitation

    Mass-spectrometry has been used to identify and assess levels of allele-specific transcription factor binding and define disease-associated allelic regions of the genome.

    “Mass-spectrometry has also been used to identify and assess levels of allele-specific transcription factor binding (ASB) and define allelic regions of the genome that are disease-associated86.”
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    Premisecitation

    An example pQTL not detected in RNA-level analysis lies in the 3′UTR of IMPA1, a putative lithium target, and may be responsible for post-transcriptional regulation of the gene.

    “An example pQTL that was not detected in RNA-level analysis lies in the 3′UTR of the IMPA1 gene, a putative target for lithium90, and may be responsible for the post-transcriptional regulation of the expression of the gene.”
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    Premisecitation

    Alternative splicing is a highly tissue-specific process that greatly increases complexity of potential RNA molecules from multi-exon genes.

    “Alternative splicing (AS) is a highly tissue-specific process18 that greatly increases the complexity of the potential set of RNA molecules produced from multi-exon genes.”
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    • cites [18] Licatalosi, D.D. et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456, 464–469 (2008). source

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    Premisecitation

    Several mis-sense RDDs in the AMPA receptor are edited at specific stages of human brain development and are required for normal brain function and phenotype in mice.

    “Several mis-sense RDDs in the AMPA receptor are edited at specific stages of human brain development78 and are required for normal brain function and phenotype in mice79.”
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    Premisecitation

    Databases of peptide identifications such as PRIDE and Peptide Atlas are valuable for mapping spectra based on previously identified peptides, but are of limited use to non-experts desiring higher-level protein information.

    “Databases of peptide identifications such as PRIDE92 and Peptide Atlas93 are valuable resources for mapping spectra based on previously identified peptides; however they are of limited use to non-experts who may simply desire higher-level information about proteins observed in a given disease state, tissue, or cellular compartment94.”
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    Premisecitation

    The serotonin receptor 5-HT2CR contains numerous RDDs that alter expressed protein sequence and cause an order of magnitude reduction in efficacy of receptor interaction with G proteins.

    “The serotonin receptor 5-HT2CR contains numerous RDDs that alter both the expressed protein sequence80 and cause an order of magnitude reduction in efficacy in the interaction of the receptor with its G proteins81.”
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    Interpretationreasoning

    This dominant transcript finding has direct consequences for differential isoform usage between CNS cell types and for progression of neurological disorders affecting protein-protein interactions, as exemplified in the Autism Spliceform Interaction Network.

    “This has direct consequences for differential isoform usage between CNS cell types and for the progression of neurological disorders affecting protein-protein interactions, as exemplified in the Autism Spliceform Interaction Network72.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Reliable identification of RDDs is technically challenging, which has led to false-positive identifications.

    “Unfortunately reliable identification of RDDs is technically challenging, which has led to false-positive identifications82.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Validation of splicing events by mass-spectrometry is feasible, either by determining abundance of known isoforms in a cell type or verifying novel exon junctions identified by RNA-sequencing, but has not yet been systematically applied to the CNS.

    “Validation of splicing events by mass-spectrometry is feasible (see Figure 1), either in terms of determining the abundance of known isoforms in a given cell-type, or verifying the existence of novel exon junctions identified by RNA-sequencing69, but has not yet been systematically applied to the CNS.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • May combine two claims.

    Interpretationreasoning

    Transcriptomic analysis alone is insufficient to accurately define the cohort of protein coding sequences, even when combined with ribosome profiling, and predictions must be refined using high-throughput proteome profiling.

    “Transcriptomic analysis alone is therefore insufficient to accurately define the cohort of protein coding sequences, even when combined with ribosome profiling, and predictions must be refined using high-throughput proteome profiling.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The poor correlation between RNA and protein abundance is likely due to a combination of biological and technical factors, including cellular heterogeneity, alternative splicing, post-transcriptional regulation, PTMs, protein turnover, and protein localisation.

    “The cause for this poor correlation is likely the result of a combination of biological and technical factors57; where biological factors include cellular heterogeneity, alternative splicing, post-transcriptional regulation, post-translational modifications, protein-turnover, and protein localisation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Li, J.J., Bickel, P.J. & Biggin, M.D. System wide analyses have underestimated protein abundances and the importance of transcription in mammals. PeerJ 2, e270 (2014). source

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    Premisecitation

    Detection of ASE relies on discovery of heterozygous genomic variants that allow monitoring imbalances in RNA abundance from each parental allele; mis-sense variants enable detection of ASE by mass-spectrometry.

    “Detection of ASE relies on the discovery of heterozygous genomic variants that allow monitoring imbalances in the abundance of RNA produced from each parental allele; with mis-sense (non-synonymous) variants enabling detection of ASE by mass-spectrometry84.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] Khan, Z. et al. Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS. Mol. Syst. Biol. 8, 602 (2012). source

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    Premisecitation

    QTL have been extensively mapped to complex traits using transcriptomics (eQTL), and more recently variants have been related to protein abundance (pQTL).

    “Quantitative trait loci (QTL) have been extensively mapped to a variety of complex traits using transcriptomics in terms of the relationship between genomic variants and RNA expression (eQTL) and, more recently, variants have also been related to protein abundance (pQTL)87.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Splicing in the brain has been extensively profiled using transcriptomics, and specific alternative transcript usage has been implicated in neuropsychiatric disorders.

    “Splicing in the brain has been extensively profiled using transcriptomics and specific instances of alternative transcript usage have been implicated in neuropsychiatric disorders11.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Johnson, M.B. et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62, 494–509 (2009). source

      Not checked in the free run.

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    Premisecitation

    Pulse-labelling SILAC proteomics and biotin-puromycin labelling can assay production and degradation of polypeptides.

    “In a somewhat related manner to ribosomal profiling, at the protein level it is possible to assay the production and degradation of polypeptides by either pulse-labelling SILAC proteomics64 or the capture of nascent peptide chains as they are synthesised by the ribosome using biotin-puromycin labelling65.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Proteomic databases exist for plant species and human tissues, but public data on protein localisation and abundance across the brain are far less mature than RNA equivalent.

    “Proteomic databases exist for plant species95 and, more recently, for human tissues9,23 but public data on protein localisation and abundance across the brain are currently far less mature than their RNA equivalent.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [95] Sun, Q. et al. PPDB, the Plant Proteomics Database at Cornell. Nucleic Acids Res. 37, D969–D974 (2009). source

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    • cites [9] Uhlen, M. et al. Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 28, 1248–1250 (2010). source

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    • cites [23] Wilhelm, M. et al. Mass-spectrometry–based draft of the human proteome. Nature 509, 582–587 (2014). source

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    Premisecitation

    Mass cytometry can measure 10-100s of proteins in single cells at sub-cellular resolution, but low throughput currently limits the technique.

    “A potential solution may be application of mass-cytometry to measure 10–100s of proteins in single cells at sub-cellular resolution, however low-throughput currently limits this technique110.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Giesen, C. et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Methods 11, 417–422 (2014). source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Purification of striatal nuclei by NEUN labelling led to observations of adult human neurogenesis in the hippocampus.

    “purification of striatal nuclei by NEUN labelling has led to interesting observations of adult human neurogenesis in the hippocampus113”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Spalding, K.L. et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219–1227 (2013). source

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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Multimodal functional genomic analyses can be substantially enhanced by deep integration of proteomic data.

    “Multimodal functional genomic analyses can be substantially enhanced with deep integration of proteomic data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    Modeling the circuitry of the brain can only be a realistic goal when there is a comprehensive understanding of its constituent parts, including a more precise definition of the large number of neuronal cells based on both connectivity and internal proteomes.

    “Modeling the circuitry of the brain can only ever be a realistic goal when there exists a comprehensive understanding of its constituent parts, including a much more precise definition of the large number of neuronal cells based on both their connectivity and their internal proteomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Isolating neuronal cells by LCM is time-consuming and not guaranteed to yield cell-type specificity because of cellular proximity and overlapping processes.

    “isolating neuronal cells by LCM is a time-consuming process and is not guaranteed to result in cell-type specificity due to cellular proximity and overlapping processes”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The direct utility of immunoaffinity or TRAP methods for whole-proteome analysis is currently more limited than whole-genome or whole-transcriptome profiling.

    “the direct utility of immunoaffinity or TRAP methods for whole-proteome analysis is currently somewhat more limited than whole-genome or whole-transcriptome profiling”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Software and choice of parameters for peak-picking, peptide identification, PTM identification, and quantification remain a significant source of information loss and variability, and software use is often vendor-dependent.

    “However the software and choice of parameters for peak-picking, peptide identification, PTM identification, and quantification remains a significant source of information-loss and variability97 and the use of software is often dependent on vendor.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Bell, A.W. et al. A HUPO test sample study reveals common problems in mass spectrometry–based proteomics. Nat. Methods 6, 423–430 (2009). source

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  • May combine two claims.

    Premisecitation

    Following cocaine administration, DARPP-32 phosphorylation is increased in D1-receptor neurons but almost equally decreased in D2-receptor neurons.

    “following cocaine administration DARPP-32 phosphorylation is increased in D1-receptor neurons but almost equally decreased in D2-receptor neurons124”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Bateup, H.S. et al. Cell type–specific regulation of DARPP-32 phosphorylation by psychostimulant and antipsychotic drugs. Nat. Neurosci. 11, 932–939 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Existing whole-tissue analyses, even with careful manual dissection, are not sensitive to inter- or intra-cellular variability, and functional genomic information is diluted among different classes of intermixed neurons and high proportion of glial cells.

    “Existing whole-tissue analyses10, even combined with careful manual dissection are not sensitive to inter- or intra-cellular variability and, as a result, functional genomic information is ‘diluted’ amongst different classes of intermixed neurons and the high proportion of glial cells.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Kang, H.J. et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489 (2011). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    There has been recent interest in leveraging RNA-seq sequence variants to improve peptide identification, resulting in basic software tools for integration.

    “Additionally, there has been some recent interest in leveraging sequence variants obtained from RNA-seq to improve peptide identification99,100, which have in turn resulted in the production of somewhat basic software tools for integration of such datasets101.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [99] Lopez-Casado, G. et al. Enabling proteomic studies with RNA-Seq: the proteome of tomato pollen as a test case. Proteomics 12, 761–774 (2012). source

      Not checked in the free run.

    • cites [100] Wang, X. et al. Protein identification using customized protein sequence databases derived from RNA-Seq data. J. Proteome Res. 11, 1009–1017 (2012). source

      Not checked in the free run.

    • cites [101] Wang, X. & Zhang, B. customProDB: an R package to generate customized protein databases from RNA-Seq data for proteomics search. Bioinformatics 29, 3235–3237 (2013). source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The primary advantage of TRAP is that it eliminates the need to purify cells; all cells are lysed and processed, and specificity is achieved through immunoprecipitation.

    “The primary advantage of the TRAP approach is the elimination of the need to purify cells, instead all cells are lysed and processed, regardless of cell-type, and specificity is achieved through immunoprecipitation.”
    Quote in the paperSubstantial claim
41 of 41

  • The paper relies on this without support.

    Multi-modal profiling of the same single cell is currently impossible.

    “An obvious limitation is that multi-modal profiling of the same single cell is currently impossible and, as such, regulatory relationships between the dynamics of RNA transcription, regulation, and translation would still need to be inferred, rather than directly observed.”

  • The paper relies on this without support.

    The throughput and resolving power of single-cell approaches are still too low to meaningfully assess responses of collections of neurons to experimental conditions.

    “Additionally, the throughput and resolving power of single cell approaches are still too low to meaningfully assess the response of collections of neurons in a given brain region to experimental conditions such as the chemical effect of a drug, especially when there is a requirement for multiple biologically independent subjects.”

  • The paper relies on this without support.

    Different gene annotations are often used in the analysis of RNA and protein.

    “A basic, but significant limitation is that different gene annotations are often used in the analysis of RNA and protein.”

  • The paper relies on this without support.

    Current proteomic technologies require two to three orders of magnitude more cells than equivalent RNA analysis to obtain sufficient material for proteomic interrogation.

    “current proteomic technologies require two to three orders of magnitude more cells, compared to an equivalent analysis of RNA, to be collected by LCM in order to obtain sufficient material to begin to interrogate their proteome”

  • The paper relies on this without support.

    TRAP provides increased reproducibility between experiments.

    “increased reproducibility between experiments”

  • The paper relies on this without support.

    TRAP provides high yields of RNA for sequencing.

    “high yields of RNA for sequencing”

  • The paper relies on this without support.

    Intermixing of multiple cell types remains a significant barrier to the utility of sub-cellular fractionation in the CNS.

    “the familiar issue of intermixing of multiple cell-types remains a significant barrier to the utility of this approach in the CNS”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A concerted effort to resolve the brain proteome is missing.

    “Thus, protein expression analyses are required, but a concerted effort to resolve the brain proteome is missing12.”

    From Cell type- and brain region-resolved mouse brain proteome (2015) · cites this paper as [12]

    In “Improving the compatibility of proteomics with functional genomics” (page unavailable), the paper says brain-wide protein-localisation and abundance data are far less mature than RNA data and calls for a large-scale quantitative resource. That supports a gap in resolving the brain proteome, but not the stronger assertion that a concerted effort is missing: the same section names the HUPO Brain Proteome Project, and “Challenges in assessing the proteome(s) of the CNS” describes existing studies. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Related

Authors
Kitchen, R. R., Rozowsky, J. S., Gerstein, M. B., & Nairn, A. C.
Affiliations
Yale University (US)
Corresponding author
Nairn, Angus C
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2014-10-28
Volume
17
Issue
11
Pages
1491-1499
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.3829
PMC
PMC4737617
OpenAlex
W2078481820
Cited by
63
References
126
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 14 · 2016: 5 · 2015: 7
FWCI
0.85
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (DA10044, P01DA010044, DA 018343, P30DA018343)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
neuroproteomics, cell type specificity, subcellular resolution, data integration, mass spectrometry, transcriptomics, proteomics, post-translational regulation, functional genomics, neuroanatomy
MeSH terms
Animals, Central Nervous System, Humans, Proteins, Mass Spectrometry, Gene Expression Profiling, Genomics, Proteomics

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