A meta-analysis of transcriptomic profiles of Huntington's disease patients.

Description of robust transcriptomic alterations in Huntington's disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 6...

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Autores principales:	Manuel Seefelder, Stefan Kochanek
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d06386481d4c4658aa28d97302f25e7f
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spelling	oai:doaj.org-article:d06386481d4c4658aa28d97302f25e7f2021-12-02T20:10:46ZA meta-analysis of transcriptomic profiles of Huntington's disease patients.1932-620310.1371/journal.pone.0253037https://doaj.org/article/d06386481d4c4658aa28d97302f25e7f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253037https://doaj.org/toc/1932-6203Description of robust transcriptomic alterations in Huntington's disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 661 genes with robustly altered mRNA levels in the brain and blood of HD patients, respectively. In the brain, a subnetwork of 320 genes strongly correlated with HD and was enriched in transport-related genes. Bioinformatical analysis of this subnetwork highlighted CDC42, PAK1, YWHAH, NFY, DLX1, HMGN3, and PRMT3. Moreover, we found that CREB1 can regulate 78.0% of genes whose mRNA levels correlated with HD in the blood of patients. Alterations in protein transport, metabolism, transcriptional regulation, and CDC42-mediated functions are likely central features of HD. Further our data substantiate the role of transcriptional regulators that have not been reported in the context of HD (e.g. DLX1, HMGN3 and PRMT3) and strongly suggest dysregulation of NFY and its target genes across tissues. A large proportion of the identified genes such as CDC42 were also altered in Parkinson's (PD) and Alzheimer's disease (AD). The observed dysregulation of CDC42 and YWHAH in samples from HD, AD and PD patients indicates that those genes and their upstream regulators may be interesting therapeutic targets.Manuel SeefelderStefan KochanekPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253037 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manuel Seefelder Stefan Kochanek A meta-analysis of transcriptomic profiles of Huntington's disease patients.
description	Description of robust transcriptomic alterations in Huntington's disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 661 genes with robustly altered mRNA levels in the brain and blood of HD patients, respectively. In the brain, a subnetwork of 320 genes strongly correlated with HD and was enriched in transport-related genes. Bioinformatical analysis of this subnetwork highlighted CDC42, PAK1, YWHAH, NFY, DLX1, HMGN3, and PRMT3. Moreover, we found that CREB1 can regulate 78.0% of genes whose mRNA levels correlated with HD in the blood of patients. Alterations in protein transport, metabolism, transcriptional regulation, and CDC42-mediated functions are likely central features of HD. Further our data substantiate the role of transcriptional regulators that have not been reported in the context of HD (e.g. DLX1, HMGN3 and PRMT3) and strongly suggest dysregulation of NFY and its target genes across tissues. A large proportion of the identified genes such as CDC42 were also altered in Parkinson's (PD) and Alzheimer's disease (AD). The observed dysregulation of CDC42 and YWHAH in samples from HD, AD and PD patients indicates that those genes and their upstream regulators may be interesting therapeutic targets.
format	article
author	Manuel Seefelder Stefan Kochanek
author_facet	Manuel Seefelder Stefan Kochanek
author_sort	Manuel Seefelder
title	A meta-analysis of transcriptomic profiles of Huntington's disease patients.
title_short	A meta-analysis of transcriptomic profiles of Huntington's disease patients.
title_full	A meta-analysis of transcriptomic profiles of Huntington's disease patients.
title_fullStr	A meta-analysis of transcriptomic profiles of Huntington's disease patients.
title_full_unstemmed	A meta-analysis of transcriptomic profiles of Huntington's disease patients.
title_sort	meta-analysis of transcriptomic profiles of huntington's disease patients.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d06386481d4c4658aa28d97302f25e7f
work_keys_str_mv	AT manuelseefelder ametaanalysisoftranscriptomicprofilesofhuntingtonsdiseasepatients AT stefankochanek ametaanalysisoftranscriptomicprofilesofhuntingtonsdiseasepatients AT manuelseefelder metaanalysisoftranscriptomicprofilesofhuntingtonsdiseasepatients AT stefankochanek metaanalysisoftranscriptomicprofilesofhuntingtonsdiseasepatients
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A meta-analysis of transcriptomic profiles of Huntington's disease patients.

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