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Canonical genetic signatures of the adult human brain

2015; Nature Portfolio; Volume: 18; Issue: 12 Linguagem: Inglês

10.1038/nn.4171

1546-1726

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

Functional Brain Connectivity Studies

The authors applied a correlation-based metric, ‘differential stability’ (DS), to assess reproducibility of gene expression patterning across individual brains, revealing mesoscale genetic organization. The highest DS genes were enriched for brain-related biological annotations, disease associations and drug targets, and their anatomical expression pattern correlated with resting state functional connectivity. 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.