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Nat Neurosci. 2015 Dec;18(12):1832-44. doi: 10.1038/nn.4171. Epub 2015 Nov 16.

Canonical genetic signatures of the adult human brain.

Author information

1
The Allen Institute for Brain Science, Seattle, Washington, USA.
2
Division of Biomedical Informatics, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA.
3
Department of Anatomy and Neurobiology, Washington University, St. Louis, Missouri, USA.
4
Center for Complex Networks Research, Northeastern University, Boston, Massachusetts, USA.
5
Department of Physics, Northeastern University, Boston, Massachusetts, USA.
6
Center for Network Science, Central European University, Budapest, Hungary.
7
Department of Mathematical Sciences, Xi'an Jiaotong-Liverpool University, Jiangsu, China.
8
Department of Electrical Engineering and Computing Systems, University of Cincinnati, Cincinnati, Ohio, USA.
9
Institute for Protein Design, University of Washington, Seattle, Washington, USA.
10
Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
11
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
12
Department of Neuroscience, Georgetown University, Washington, DC, USA.
13
Department of Radiology, The University of Washington, Seattle, Washington, USA.

Abstract

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry.

PMID:
26571460
PMCID:
PMC4700510
DOI:
10.1038/nn.4171
[Indexed for MEDLINE]
Free PMC Article

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