title: Canonical genetic signatures of the adult human brain.
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.
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hawrylycz
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Vilas
authors.initials: V
authors.lastname: Menon
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: David
authors.initials: D
authors.lastname: Feng
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Dolbeare
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Guillozet-Bongaarts
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA.
authors.forename: Anil G
authors.identifier: http://orcid.org/0000-0002-4881-7752
authors.initials: AG
authors.lastname: Jegga
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Chang-Kyu
authors.initials: CK
authors.lastname: Lee
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Department of Anatomy and Neurobiology, Washington University, St. Louis, Missouri, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Glasser
authors.affiliation: Department of Anatomy and Neurobiology, Washington University, St. Louis, Missouri, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Dierker
authors.affiliation: Center for Complex Networks Research, Northeastern University, Boston, Massachusetts, USA.|Department of Physics, Northeastern University, Boston, Massachusetts, USA.|Center for Network Science, Central European University, Budapest, Hungary.
authors.forename: Jörg
authors.identifier: http://orcid.org/0000-0002-1583-6404
authors.initials: J
authors.lastname: Menche
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Szafer
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Forrest
authors.initials: F
authors.lastname: Collman
authors.affiliation: Department of Mathematical Sciences, Xi'an Jiaotong-Liverpool University, Jiangsu, China.
authors.forename: Pascal
authors.initials: P
authors.lastname: Grange
authors.affiliation: Department of Electrical Engineering and Computing Systems, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Berman
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mihalas
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Institute for Protein Design, University of Washington, Seattle, Washington, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Stewart
authors.affiliation: Center for Complex Networks Research, Northeastern University, Boston, Massachusetts, USA.|Department of Physics, Northeastern University, Boston, Massachusetts, USA.|Center for Network Science, Central European University, Budapest, Hungary.|Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Albert-László
authors.initials: AL
authors.lastname: Barabási
authors.affiliation: Department of Neuroscience, Georgetown University, Washington, DC, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Schulkin
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: John
authors.initials: J
authors.lastname: Phillips
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Ng
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Chinh
authors.initials: C
authors.lastname: Dang
authors.affiliation: Department of Radiology, The University of Washington, Seattle, Washington, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Haynor
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Jones
authors.affiliation: Department of Anatomy and Neurobiology, Washington University, St. Louis, Missouri, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Van Essen
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Christof
authors.initials: C
authors.lastname: Koch
authors.affiliation: The Allen Institute for Brain Science, Seattle, Washington, USA.
authors.forename: Ed
authors.initials: E
authors.lastname: Lein
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D051379:Mice; D009415:Nerve Net / Q000502:physiology*; D059467:Transcriptome / Q000235:genetics*