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Sci Rep. 2017 Apr 18;7(1):897. doi: 10.1038/s41598-017-00952-9.

Global gene expression profiling of healthy human brain and its application in studying neurological disorders.

Negi SK1, Guda C2,3,4,5.

Author information

1
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
2
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA. babu.guda@unmc.edu.
3
Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA. babu.guda@unmc.edu.
4
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. babu.guda@unmc.edu.
5
Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA. babu.guda@unmc.edu.

Abstract

Brain function is governed by precise regulation of gene expression across its anatomically distinct structures; however, the expression patterns of genes across hundreds of brain structures are not clearly understood. Here, we describe a gene expression model, which is representative of the healthy human brain transcriptome by using data from the Allen Brain Atlas. Our in-depth gene expression profiling revealed that 84% of genes are expressed in at least one of the 190 brain structures studied. Hierarchical clustering based on gene expression profiles delineated brain regions into structurally tiered spatial groups and we observed striking enrichment for region-specific processes. Further, weighted co-expression network analysis identified 19 robust modules of highly correlated genes enriched with functional associations for neurogenesis, dopamine signaling, immune regulation and behavior. Also, structural distribution maps of major neurotransmission systems in the brain were generated. Finally, we developed a supervised classification model, which achieved 84% and 81% accuracies for predicting autism- and Parkinson's-implicated genes, respectively, using our expression model as a baseline. This study represents the first use of global gene expression profiling from healthy human brain to develop a disease gene prediction model and this generic methodology can be applied to study any neurological disorder.

PMID:
28420888
PMCID:
PMC5429860
DOI:
10.1038/s41598-017-00952-9
[Indexed for MEDLINE]
Free PMC Article

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