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Cited by 3,083Single-cell and spatial transcriptomicsGene expression and cancer classificationBioinformatics and Genomic Networks

An anatomically comprehensive atlas of the adult human brain transcriptome

Open access
Hawrylycz, Michael J., Lein, Ed S., Guillozet-Bongaarts, Angela L., Shen, Elaine H., Ng, Lydia, Miller, Jeremy A., van de Lagemaat, Louie N., Smith, Kimberly A. +59 more·2012·Nature
DOI 10.1038/nature11405PMC PMC4243026
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Abstract

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography—the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.

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Crossref · 10.1038/nature11405

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    These region- and cell-type molecular signatures are highly conserved between individuals.

    “that are highly conserved between individuals”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The two or three clinically unremarkable adult male brains studied are sufficiently representative of the adult human brain for the atlas's general conclusions.
  • Findingown data

    The percentage of PSD genes with highly regional differential expression (31%) is significantly greater than the percentage observed across all genes (21%).

    “a significantly greater percentage than that observed across all genes (21%, P < 10−6, Mann–Whitney U-test).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.
  • Findingown data

    Tyrosine hydroxylase is enriched in the substantia nigra pars compacta, ventral tegmental area, hypothalamic supraoptic and preoptic nuclei, and locus ceruleus.

    “tyrosine hydroxylase (TH) is enriched in the substantia nigra pars compacta (SNC), ventral tegmental area (VTA), and hypothalamic supraoptic and preoptic nuclei, as well as in the locus ceruleus”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.
  • Findingown data

    Brain-wide transcriptional variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia.

    “brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.
  • Findingown data

    No statistically significant hemispheric differences at the fine structural level were corroborated in both brains.

    “no statistically significant hemispheric differences could be identified at this fine structural level that were corroborated in both brains (paired one-sided t-tests, P < 0.01, Benjamini–Hochberg (BH)-corrected).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The two or three clinically unremarkable adult male brains studied are sufficiently representative of the adult human brain for the atlas's general conclusions.
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 11
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    The neocortex has distinct transcriptional features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression.

    “with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The two or three clinically unremarkable adult male brains studied are sufficiently representative of the adult human brain for the atlas's general conclusions.
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    One hundred and seventy distinct structures were assayed at least once in both brains, and 146 structures were assayed twice or more.

    “One-hundred and seventy distinct structures were assayed at least once in both brains, and 146 structures twice or more (Supplementary Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    One highly regionalized neuron-related module (M6) was enriched in the striatum, with DRD1 as a hub gene.

    “One highly regionalized neuron-related module (M6) was enriched in the striatum (the dopamine receptorDRD1 in Fig. 2a is a hub gene).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    The gene modules identified in Brain 1 were well conserved in Brain 2 as a whole, both at the level of regional gene expression patterns and by a module preservation index.

    “The gene modules identified in Brain 1 were well conserved in Brain 2 as a whole (Fig. 3b), both at the level of regional gene expression patterns (third row) and as measured by a module preservation index (fourth row) using a summary Z-statistic as described previously20.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Langfelder, P., Luo, R., Oldham, M. C. & Horvath, S. Is my network module preserved and reproducible? PLoS Comput. Biol. 7, e1001057 (2011) source

      Not checked in the free run.

    • Rests on an assumption: The two or three clinically unremarkable adult male brains studied are sufficiently representative of the adult human brain for the atlas's general conclusions.
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

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

    Findingown data

    The results in Fig. 4b bear strong similarity to the plot in Fig. 4a, with the neocortex and cerebellum displaying the least internal heterogeneity.

    “The results in Fig. 4b bear strong similarity to the plot in Fig. 4a, again with the neocortex and cerebellum displaying the least internal heterogeneity.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    Applied to the entire 911 sample set from Brain 1, genes were grouped into well-defined co-expression modules with specific anatomical distributions, consistent with previous studies.

    “Applied to the entire 911 sample set from Brain 1, genes were grouped into well-defined co-expression modules with specific anatomical distributions (Fig. 3a, b), consistent with previous studies in brain tissues18, 19.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Oldham, M. C. et al. Functional organization of the transcriptome in human brain. Nature Neurosci. 11, 1271–1282 (2008) source

      Not checked in the free run.

    • cites [19] Miller, J. A., Horvath, S. & Geschwind, D. H. Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways. Proc. Natl Acad. Sci. USA 107, 12698–12703 (2010) source

      Not checked in the free run.

    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    The relative position of each lobe's samples reflects cortical topography, with the frontal pole and occipital striate cortex at opposite ends and precentral gyrus near postcentral gyrus.

    “the relative position of each lobe’s samples reflects the cortical topography, with the frontal pole and occipital striate cortex at opposite ends, precentral gyrus near postcentral gyrus, and so on.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Samples from each lobe group together, and the relative positions of the lobes are anatomically correct.

    “Not only do samples from each lobe group together, but the relative positions of the lobes are anatomically correct.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The globus pallidus and striatum have highly distinct profiles, as do several specific subcortical regions including the midbrain raphe, pontine nuclei and inferior olivary complex.

    “The globus pallidus and striatum have highly distinct profiles, as do several specific subcortical regions including the midbrain raphe, pontine nuclei and inferior olivary complex.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    Other modules showed subcortical enrichment and correspond to expression in different types of glia (M8-M12), including microglia, astrocytes and oligodendrocytes.

    “Other modules showed subcortical enrichment and correspond to expression in different types of glia (M8–M12), including microglia, astrocytes and oligodendrocytes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Findingown data

    The MDS distance effect is strongest when limited to genes differential between gyri, but can also be seen using the entire ~30,000 gene set, achieving a fit of 12.48% (P < 10−4).

    “This effect is strongest when limited to genes that are differential between gyri as above, but can also be seen using the entire ~30,000 gene set, achieving a fit of 12.48% between native and MDS coordinates (P < 10−4, Supplementary Fig. 10).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MDS-based sample correlations vary nearly linearly with 3D physical distance, with a goodness of fit between native and MDS coordinates of 28.36% (P < 10−4).

    “MDS-based sample correlations vary nearly linearly with 3D physical distance (Fig. 6e, inset), with a goodness of fit between native and MDS coordinates of 28.36% (P < 10−4, Supplementary Fig. 9).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The first three principal components had striking selectivity for specific cortical regions and were generally reproducible across both brains.

    “the first three principal components had striking selectivity for specific cortical regions (samples ordered by lobe and roughly rostral to caudal within each lobe) and were generally reproducible across both brains.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The first three principal components accounted for specific variance percentages in Brain 1 and Brain 2: PC1 58% and 42%, PC2 10% and 11%, PC3 5% and 8%, respectively.

    “These first three components accounted for a large amount of the variance (PC1: 58% in Brain 1, 42% in Brain 2; PC2: 10% in Brain 1, 11% in Brain 2; PC3: 5% in Brain 1, 8% in Brain 2; Supplementary Fig. 8).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. The quote only partly states this claim.

    Findingown data

    Differential expression across hippocampal subfields was validated by in situ hybridization.

    “Differential expression across hippocampal subfields could be validated by ISH.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Thirty-eight transcripts demonstrated high correlation with the striatal module (M6), and 87 transcripts with the oligodendrocyte-associated module (M12).

    “38 transcripts demonstrated high correlation with the striatal module (M6), and 87 transcripts with the oligodendrocyte-associated module (M12; Fig. 3c)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

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

    Premisecitation

    Conservation and divergence in brain function between humans and other species provide essential information for understanding drug action, which is often poorly conserved across species.

    “conservation and divergence in brain function between humans and other species provide essential information for the understanding of drug action, which is often poorly conserved across species6.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Markou, A., Chiamulera, C., Geyer, M. A., Tricklebank, M. & Steckler, T. Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology 34, 74–89 (2009) source

      Not checked in the free run.

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

    Premisecitation

    This percentage is consistent with the percentage of genes expressed in mouse brain by ISH (80%) and fetal human brain by microarrays (76%).

    “consistent with the percentage of genes expressed in mouse brain by ISH (80%; ref. 1) and fetal human brain by microarrays (76%; ref. 11).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007) source

      Not checked in the free run.

    • cites [11] Johnson, M. B. et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62 494–509 S0896–6273(09)00286–4 (2009) source

      Not checked in the free run.

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

    Premisecitation

    This absence of hemispheric differences is consistent with a recent study of developing human neocortex that failed to identify hemispheric differences.

    “this finding is consistent with a recent study of developing human neocortex that failed to identify hemispheric differences despite extensive efforts using microarrays and quantitative PCR11.”
    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 S0896–6273(09)00286–4 (2009) source

      Not checked in the free run.

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

    Premisecitation

    In rodents, brain- and transcriptome-wide cellular-resolution maps of transcript distributions are useful resources to complement genomic sequence data.

    “In rodents, brain- and transcriptome-wide, cellular-resolution maps of transcript distributions are widely useful resources to complement genomic sequence data1, 2, 3.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007) source

      Not checked in the free run.

    • cites [2] Diez-Roux, G. et al. A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol. 9, e1000582 (2011) source

      Not checked in the free run.

    • cites [3] Baldock, R. A. et al. EMAP and EMAGE: a framework for understanding spatially organized data. Neuroinformatics 1, 309–325 (2003) source

      Not checked in the free run.

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

    Premisecitation

    The human excitatory postsynaptic density contains 740 genes.

    “we examined the 740 genes identified in the human excitatory postsynaptic density (PSD12)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Bayes, A. et al. Characterization of the proteome, diseases and evolution of the human postsynaptic density. Nature Neurosci. 14, 19–21 (2011) source

      Not checked in the free run.

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

    Study design and conductnone given

    Gyral patterns do not correlate perfectly with either cytoarchitectural or functional cortical parcellation.

    “gyral patterns do not correlate perfectly with either cytoarchitectural or functional cortical parcellation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    RNA quality was tested and specimens with an RNA integrity number greater than 6 were used.

    “testing for RNA quality (RNA integrity number >6)”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Neurofilament proteins NEFL, NEFM and NEFH are frequently enriched in long-range projection neurons.

    “which are frequently enriched in long-range projection neurons14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Hof, P. R., Nimchinsky, E. A. & Morrison, J. H. Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices. J. Comp. Neurol. 362, 109–133 (1995) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Synapse-associated genes clustered into groups enriched in specific regions, indicating a diverse set of excitatory synapse subtypes.

    “The synapse-associated genes clustered into groups enriched in specific regions, indicative of a diverse set of excitatory synapse subtypes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Study design and conductreasoning

    The two individuals assayed were males of similar age and ethnicity and therefore do not capture population or sex diversity.

    “These two individuals were males of similar age and ethnicity and therefore do not capture population or sex diversity”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The relative homogeneity of the two largest neuronal structures (cerebellar cortex and cortex) is striking and suggests an evolutionary expansion of a canonical cortical blueprint.

    “the relative homogeneity of the two largest neuronal structures, with ~69 billion (cerebellar cortex) and ~16 billion (cortex) neurons out of the 86 billion neurons in the human brain33, is striking and suggests an evolutionary expansion of a canonical cortical blueprint34.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [33] Herculano-Houzel, S. The human brain in numbers: a linearly scaled-up primate brain. Front. Hum. Neurosci. 3, 31 (2009) source

      Not checked in the free run.

    • cites [34] Douglas, R. J. & Martin, K. A. Neuronal circuits of the neocortex. Annu. Rev. Neurosci. 27, 419–451 (2004) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    This suggests that many genes may be quite pleiotropic with respect to brain function, and that local gene regulation in specific cytoarchitectural nuclei is the most important level of resolution.

    “This suggests that many genes may be quite pleiotropic with respect to brain function, and that local gene regulation in specific cytoarchitectural nuclei is the most important level of resolution.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

  • May combine two claims.

    Interpretationown data

    The high degree of similarity between the two brains is suggestive of a strong underlying common blueprint for the human brain transcriptome and is consistent with other recent studies of human neocortical gene expression.

    “this high degree of similarity is suggestive of a strong underlying common blueprint for the human brain transcriptome and is consistent with other recent studies of human neocortical gene expression4, 5”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4] Kang, H. J. et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489 (2011) source

      Not checked in the free run.

    • cites [5] Colantuoni, C. et al. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478, 519–523 (2011) source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Specimens used for profiling had no known neuropsychiatric or neuropathological history.

    “specimens with no known neuropsychiatric or neuropathological history were collected”
    Quote in the paperSubstantial claim
30 of 30

  • The paper relies on this without support.

    The two or three clinically unremarkable adult male brains studied are sufficiently representative of the adult human brain for the atlas's general conclusions.

    “Two complete normal male brains were analysed from donors aged 24 and 39 years”
    “in a small number of high-quality, clinically unremarkable brains”

  • The paper relies on this without support.

    Microarray transcript levels measured in post-mortem brain tissue reflect the in vivo transcriptional state of the corresponding brain regions.

    “RNA was isolated from each sample and used to generate labelled cRNA probes for hybridization to custom 64K Agilent microarrays.”
    “The output of the data generation pipeline described above is a detailed quantitative map of transcript distribution across the entire brain.”

  • The paper relies on this without support.

    The primary feature distinguishing the human brain from other species is the enormous expansion of the neocortex relative to total brain volume.

    “The primary feature that distinguishes the human brain from that of other species is the enormous expansion of the neocortex relative to total brain volume.”
3 of 3

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?

  • The AHBA data were corrected for batch effects and normalized to the 75% quantile, and BSS data were quantile normalized.

    “The AHBA data were corrected for batch effects and normalized to the 75% quantile, as previously described (Hawrylycz et al., 2012). BSS data also were quantile normalized.”

    From Aerobic glycolysis in the human brain is associated with development and neotenous gene expression (2014) · cites this paper as Hawrylycz et al., 2012

    The Methods sections on Sample processing and Microarray data analysis describe how the AHBA microarrays were generated and analyzed, but do not specify batch-effect correction or normalization to the 75th quantile. Searches for “batch effect,” “quantile,” and “75% quantile” found no passage establishing those steps. The citation is attached to the AHBA statement; the separate BSS normalization statement is not attributed to this source. Page numbers were not available in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • The Allen Brain Institute and BrainSpan have evaluated spatial and temporal transcriptomes.

    “Recent important advances include the evaluation of spatial and temporal transcriptomes by the Allen Brain Institute and BrainSpan8,11–13”

    From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [12]

  • When evaluating co-expression across brain regions, hubs in modules associated with specific regions, such as the cerebellum, are usually markers for predominant cell types, such as granule cells.

    “For example, when evaluating co-expression across brain regions, hubs in modules that are associated with specific regions, such as the cerebellum, are usually markers for predominant cell types, such as granule cells11,12,26,32.”

    From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [12]

  • Network approaches are particularly useful for relating whole-tissue-level changes to high-resolution experiments.

    “Network approaches are particularly useful for relating whole-tissue-level changes to data from these high-resolution experiments11–13,26 (FIG. 2a).”

    From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [12]

  • Network analysis can identify multiple levels of molecular organization within the hierarchy of brain region, cell type, organelle and molecular pathways using only transcriptional data, and can enable integration with other information.

    “A major advantage of network analysis over DGE analysis is that it can identify multiple levels of molecular organization within the hierarchy of brain region, cell type, organelle and molecular pathways using only transcriptional data, and can thus enable integration with other information, such as known pathway annotations, protein interactions and other molecular profiling data11,12,26,27”

    From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [12]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Hurd, Y. L. & Hall, H. in Handbook of Chemical Neuroanatomy. (Dopamine) (eds Dunnett, S.B., Bentivoglio, M., Bjorklund, A., & Hokfelt, T. ) Ch. IX 525–571 (Elsevier, 2005)

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Authors
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., Abajian, C., Beckmann, C. F., Bernard, A., Bertagnolli, D., Boe, A. F., Cartagena, P. M., Chakravarty, M. M., Chapin, M., Chong, J., Dalley, R. A., Daly, B. D., Dang, C., Datta, S., Dee, N., Dolbeare, T. A., Faber, V., Feng, D., Fowler, D. R., Goldy, J., Gregor, B. W., Haradon, Z., Haynor, D. R., Hohmann, J. G., Horvath, S., Howard, R. E., Jeromin, A., Jochim, J. M., Kinnunen, M., Lau, C., Lazarz, E. T., Lee, C., Lemon, T. A., Li, L., Li, Y., Morris, J. A., Overly, C. C., Parker, P. D., Parry, S. E., Reding, M., Royall, J. J., Schulkin, J., Sequeira, P. A., Slaughterbeck, C. R., Smith, S. C., Sodt, A. J., Sunkin, S. M., Swanson, B. E., Vawter, M. P., Williams, D., Wohnoutka, P., Zielke, H. R., Geschwind, D. H., Hof, P. R., Smith, S. M., Koch, C., Grant, S. G. N., & Jones, A. R.
Affiliations
  • Allen Institute for Brain Science (US)
  • Radboud University Nijmegen (NL)
  • University of California, Irvine (US)
  • University of Maryland Medical Center (US)
  • University of Maryland, Baltimore (US)
  • University of Washington (US)
  • Banyan Biomarkers (United States) (US)
  • Georgetown University (US)
  • University of California, Los Angeles (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • University of Oxford (GB)
  • University of Edinburgh (GB)
Corresponding author
Hawrylycz, Michael J.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2012-09
Volume
489
Issue
7416
Pages
391-399
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature11405
PMC
PMC4243026
OpenAlex
W2055655674
Semantic Scholar
44c6c5a71047351f81db358eabf87882c5232718
Cited by
3,083
References
36
Citations by year
2026: 341 · 2025: 365 · 2024: 320 · 2023: 259 · 2022: 267 · 2021: 274 · 2020: 243 · 2019: 173 · 2018: 165 · 2017: 163 · 2016: 169 · 2015: 134 · 2014: 123 · 2013: 72 · 2012: 10
FWCI
43.61
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • University of Twente Research Information (submittedVersion)
Funders
  • U.S. Department of Health and Human Services
  • Wellcome Trust (066717, 077155)
  • European Commission (241498, 242167, 241995)
  • Health Resources and Services Administration
  • National Institute of Standards and Technology
  • U.S. Public Health Service (1C76HF15069-01-00, 1C76HF19619-01-00)
  • National Institute of Mental Health (R01MH085801, R37MH060233)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
human brain transcriptome, transcriptional atlas, gene expression mapping, differential gene expression, gene co-expression, neuronal cell types, oligodendrocytes, astrocytes, microglia, primary sensorimotor cortex, frontal lobe, calbindin-D28k, hippocampus, postmortem brain, brain cell types
MeSH terms
Adult, Anatomy, Artistic, Animals, Atlases as Topic, Brain, Dopamine, Health, Hippocampus, Humans, Macaca mulatta, Male, RNA, Messenger, Species Specificity, In Situ Hybridization, Neocortex, Internet, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Mice, Post-Synaptic Density, Transcriptome, Calbindins, S100 Calcium Binding Protein G

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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