Canonical Genetic Signatures of the Adult Human Brain

By M. Hawrylycz, Jeremy A. Miller, V. Menon, David Feng, Tim Dolbeare, A. Guillozet‐Bongaarts, Anil G. Jegga, Bruce J. Aronow, Changkyu Lee, Amy Bernard and 20 more. Nature Neuroscience, 2015

643 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Health, Toxicology and Mutagenesis, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e3aa43b55cdd5d733360a178d938565fa201667a

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In Cognitive Neuroscience

1. Stephen M. Smith
2. Matthew F. Glasser
3. Timothy Edward John Behrens
4. Jesper L. R. Andersson
5. Kamil Ugurbil
6. Timothy S. Coalson
7. Essa Yacoub
8. Mark Jenkinson

In Health, Toxicology and Mutagenesis

1. Stephen M. Smith
2. Mingxia Liu
3. Thomas E. Nichols

In Molecular Biology

1. Timothy Edward John Behrens
2. Jesper L. R. Andersson
3. Stamatios N. Sotiropoulos
4. Stephen M. Smith
5. Alex Fornito
6. Matthew F. Glasser
7. Ben D. Fulcher
8. D. V. Van Essen

Citations in the corpus

• Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017, background): “First, differences in the CNS microenvironment between species have been identified with respect to CNS gene expression 16 , the lipidome 17 and the proteome 18 .”
• A practical guide to linking brain-wide gene expression and neuroimaging data (2018, methodology): “Genes with high DS values demonstrate consistent patterns of regional variation in expression across the six AHBA subjects, and have been shown to be enriched for brain-related biological functions (Hawrylycz et al., 2015).”
• The Human Connectome Project’s Neuroimaging Approach (2016, background): “Hawrylycz et al. 96 demonstrated correlations between gene expression patterns in post-mortem human cortex and HCP-based in vivo functional connectivity.”