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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
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 ALdoi
10.1038/nn.4171subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1832-44issue
12eissn
1097-6256issn
1546-1726pii
nn.4171journal_volume
18pub_type
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