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

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 th...

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Autores principales:	Simarjeet K. Negi, Chittibabu Guda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ee9d2151e3741dbb5dc84da3763fd4b
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spelling	oai:doaj.org-article:5ee9d2151e3741dbb5dc84da3763fd4b2021-12-02T11:40:53ZGlobal gene expression profiling of healthy human brain and its application in studying neurological disorders10.1038/s41598-017-00952-92045-2322https://doaj.org/article/5ee9d2151e3741dbb5dc84da3763fd4b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00952-9https://doaj.org/toc/2045-2322Abstract 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.Simarjeet K. NegiChittibabu GudaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simarjeet K. Negi Chittibabu Guda Global gene expression profiling of healthy human brain and its application in studying neurological disorders
description	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.
format	article
author	Simarjeet K. Negi Chittibabu Guda
author_facet	Simarjeet K. Negi Chittibabu Guda
author_sort	Simarjeet K. Negi
title	Global gene expression profiling of healthy human brain and its application in studying neurological disorders
title_short	Global gene expression profiling of healthy human brain and its application in studying neurological disorders
title_full	Global gene expression profiling of healthy human brain and its application in studying neurological disorders
title_fullStr	Global gene expression profiling of healthy human brain and its application in studying neurological disorders
title_full_unstemmed	Global gene expression profiling of healthy human brain and its application in studying neurological disorders
title_sort	global gene expression profiling of healthy human brain and its application in studying neurological disorders
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5ee9d2151e3741dbb5dc84da3763fd4b
work_keys_str_mv	AT simarjeetknegi globalgeneexpressionprofilingofhealthyhumanbrainanditsapplicationinstudyingneurologicaldisorders AT chittibabuguda globalgeneexpressionprofilingofhealthyhumanbrainanditsapplicationinstudyingneurologicaldisorders
_version_	1718395518174887936

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

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