title: An anatomically comprehensive atlas of the adult human brain transcriptome.
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.
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawrylycz
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Ed S
authors.initials: ES
authors.lastname: Lein
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Guillozet-Bongaarts
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Shen
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.lastname: Ng
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Genes to Cognition Programme, Edinburgh University, Edinburgh EH16 4SB, UK.
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authors.initials: LN
authors.lastname: van de Lagemaat
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Smith
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.lastname: Ebbert
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Zackery L
authors.initials: ZL
authors.lastname: Riley
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: MIRA Institute, University of Twente & Donders Institute, Radboud University Nijmegen, Nijmegen, Netherlands.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Beckmann
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.lastname: Bernard
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.lastname: Bertagnolli
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Department of Psychiatry & Human Behavior, University of California, Irvine, California 92697, USA.
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authors.lastname: Cartagena
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA; Kimel Family Translational Imaging-Genetics Laboratory, Centre for Addiction and Mental Health Toronto, Ontario M5S 2S1, Canada.
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authors.initials: MM
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.initials: RA
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authors.affiliation: University of Maryland School of Medicine, Department of Diagnostic Radiology, University of Maryland Medical Center, Baltimore, Maryland 21201, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
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authors.initials: DR
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.lastname: Gregor
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
authors.forename: Zeb
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authors.lastname: Haradon
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington 98195, USA.
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authors.initials: DR
authors.lastname: Haynor
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Department of Human Genetics, Gonda Research Center, David Geffen School of Medicine, Los Angeles, California 90095, USA.
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authors.lastname: Horvath
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Banyan Biomarkers, Inc., Alachua, Florida 32615, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Office of the Chief Medical Examiner, Baltimore, MD, Department of Pediatrics, University of Maryland, Baltimore, Maryland 21201, USA.
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authors.lastname: Li
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Department of Neuroscience, Georgetown University, School of Medicine, Washington DC 20007, USA.
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authors.initials: PA
authors.lastname: Sequeira
authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.initials: CR
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.initials: MP
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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authors.affiliation: The Eunice Kennedy Shriver NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland, Baltimore, Maryland 21201, USA.
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authors.initials: HR
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authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
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authors.affiliation: FMRIB, Oxford University, Oxford OX3 9DU, UK.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA; Computation & Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.
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authors.affiliation: Allen Institute for Brain Science, Seattle, Washington 98103, USA.
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mesh_terms: D000328:Adult; D000716:Anatomy, Artistic; D000818:Animals; D001271:Atlases as Topic; D001921:Brain / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism*; D064026:Calbindins; D030541:Databases, Genetic; D004298:Dopamine / Q000378:metabolism; D020869:Gene Expression Profiling; D006262:Health; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D020407:Internet; D008253:Macaca mulatta / Q000033:anatomy & histology / Q000235:genetics; D008297:Male; D051379:Mice; D019579:Neocortex / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D057907:Post-Synaptic Density / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D013045:Species Specificity; D059467:Transcriptome / Q000235:genetics*
chemical_list: D064026:Calbindins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D004298:Dopamine