Canonical genetic signatures of the adult human brain

Michael Hawrylycz; Jeremy A. Miller; Vilas Menon; David Feng; Tim Dolbeare; Angela L. Guillozet-Bongaarts; Anil G. Jegga; Bruce J. Aronow; Chang Kyu Lee; Amy Bernard; Matthew F. Glasser; Donna L. Dierker; Jörg Menche; Aaron Szafer; Forrest Collman; Pascal Grange; Kenneth A. Berman; Stefan Mihalas; Zizhen Yao; Lance Stewart; Albert László Barabási; Jay Schulkin; John Phillips; Lydia Ng; Chinh Dang; David R Haynor; Allan Jones; David C. Van Essen; Christof Koch; Ed Lein

doi:10.1038/nn.4171

Canonical genetic signatures of the adult human brain

Michael Hawrylycz^*, Jeremy A. Miller, Vilas Menon, David Feng, Tim Dolbeare, Angela L. Guillozet-Bongaarts, Anil G. Jegga, Bruce J. Aronow, Chang Kyu Lee, Amy Bernard, Matthew F. Glasser, Donna L. Dierker, Jörg Menche, Aaron Szafer, Forrest Collman, Pascal Grange, Kenneth A. Berman, Stefan Mihalas, Zizhen Yao, Lance StewartAlbert László Barabási, Jay Schulkin, John Phillips, Lydia Ng, Chinh Dang, David R Haynor, Allan Jones, David C. Van Essen, Christof Koch, Ed Lein

^*Corresponding author for this work

Department of Physics

Research output: Contribution to journal › Article › peer-review

400 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1832-1844
Number of pages	13
Journal	Nature Neuroscience
Volume	18
Issue number	12
DOIs	https://doi.org/10.1038/nn.4171
Publication status	Published - 25 Nov 2015

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Hawrylycz, M., Miller, J. A., Menon, V., Feng, D., Dolbeare, T., Guillozet-Bongaarts, A. L., Jegga, A. G., Aronow, B. J., Lee, C. K., Bernard, A., Glasser, M. F., Dierker, D. L., Menche, J., Szafer, A., Collman, F., Grange, P., Berman, K. A., Mihalas, S., Yao, Z., ... Lein, E. (2015). Canonical genetic signatures of the adult human brain. Nature Neuroscience, 18(12), 1832-1844. https://doi.org/10.1038/nn.4171

@article{632683dfc65243b2a49bca6a63e8842e,

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.",

author = "Michael Hawrylycz and Miller, {Jeremy A.} and Vilas Menon and David Feng and Tim Dolbeare and Guillozet-Bongaarts, {Angela L.} and Jegga, {Anil G.} and Aronow, {Bruce J.} and Lee, {Chang Kyu} and Amy Bernard and Glasser, {Matthew F.} and Dierker, {Donna L.} and J{\"o}rg Menche and Aaron Szafer and Forrest Collman and Pascal Grange and Berman, {Kenneth A.} and Stefan Mihalas and Zizhen Yao and Lance Stewart and Barab{\'a}si, {Albert L{\'a}szl{\'o}} and Jay Schulkin and John Phillips and Lydia Ng and Chinh Dang and {R Haynor}, David and Allan Jones and {Van Essen}, {David C.} and Christof Koch and Ed Lein",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = nov,

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doi = "10.1038/nn.4171",

language = "English",

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Hawrylycz, M, Miller, JA, Menon, V, Feng, D, Dolbeare, T, Guillozet-Bongaarts, AL, Jegga, AG, Aronow, BJ, Lee, CK, Bernard, A, Glasser, MF, Dierker, DL, Menche, J, Szafer, A, Collman, F, Grange, P, Berman, KA, Mihalas, S, Yao, Z, Stewart, L, Barabási, AL, Schulkin, J, Phillips, J, Ng, L, Dang, C, R Haynor, D, Jones, A, Van Essen, DC, Koch, C & Lein, E 2015, 'Canonical genetic signatures of the adult human brain', Nature Neuroscience, vol. 18, no. 12, pp. 1832-1844. https://doi.org/10.1038/nn.4171

TY - JOUR

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AU - Hawrylycz, Michael

AU - Miller, Jeremy A.

AU - Menon, Vilas

AU - Feng, David

AU - Dolbeare, Tim

AU - Guillozet-Bongaarts, Angela L.

AU - Jegga, Anil G.

AU - Aronow, Bruce J.

AU - Lee, Chang Kyu

AU - Bernard, Amy

AU - Glasser, Matthew F.

AU - Dierker, Donna L.

AU - Menche, Jörg

AU - Szafer, Aaron

AU - Collman, Forrest

AU - Grange, Pascal

AU - Berman, Kenneth A.

AU - Mihalas, Stefan

AU - Yao, Zizhen

AU - Stewart, Lance

AU - Barabási, Albert László

AU - Schulkin, Jay

AU - Phillips, John

AU - Ng, Lydia

AU - Dang, Chinh

AU - R Haynor, David

AU - Jones, Allan

AU - Van Essen, David C.

AU - Koch, Christof

AU - Lein, Ed

PY - 2015/11/25

Y1 - 2015/11/25

N2 - 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.

AB - 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.

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U2 - 10.1038/nn.4171

DO - 10.1038/nn.4171

M3 - Article

C2 - 26571460

AN - SCOPUS:84948784579

SN - 1097-6256

VL - 18

SP - 1832

EP - 1844

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 12

ER -

Canonical genetic signatures of the adult human brain

Abstract

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