Transcriptomic differences in MSA clinical variants

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcr...

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Autores: Pérez Soriano, Alexandra, Arnal, Magdalena, Botta Orfila, Teresa, Giraldo, Darly, Fernández, Manel, Compta, Yaroslau, Fernández-Santiago, Ruben, Ezquerra, Mario, Tartaglia, Gian Gaetano, Martí, M. Josep, Catalan multiple system atrophy-registry (CMSAR)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/45499
Acceso en línea:http://hdl.handle.net/10230/45499
http://dx.doi.org/10.1038/s41598-020-66221-4
Access Level:acceso abierto
Palabra clave:Computational biology and bioinformatics
Movement disorders
Neurological disorders
Neurology
Neuroscience
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network_name_str España
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dc.title.none.fl_str_mv Transcriptomic differences in MSA clinical variants
title Transcriptomic differences in MSA clinical variants
spellingShingle Transcriptomic differences in MSA clinical variants
Pérez Soriano, Alexandra
Computational biology and bioinformatics
Movement disorders
Neurological disorders
Neurology
Neuroscience
title_short Transcriptomic differences in MSA clinical variants
title_full Transcriptomic differences in MSA clinical variants
title_fullStr Transcriptomic differences in MSA clinical variants
title_full_unstemmed Transcriptomic differences in MSA clinical variants
title_sort Transcriptomic differences in MSA clinical variants
dc.creator.none.fl_str_mv Pérez Soriano, Alexandra
Arnal, Magdalena
Botta Orfila, Teresa
Giraldo, Darly
Fernández, Manel
Compta, Yaroslau
Fernández-Santiago, Ruben
Ezquerra, Mario
Tartaglia, Gian Gaetano
Martí, M. Josep
Catalan multiple system atrophy-registry (CMSAR)
author Pérez Soriano, Alexandra
author_facet Pérez Soriano, Alexandra
Arnal, Magdalena
Botta Orfila, Teresa
Giraldo, Darly
Fernández, Manel
Compta, Yaroslau
Fernández-Santiago, Ruben
Ezquerra, Mario
Tartaglia, Gian Gaetano
Martí, M. Josep
Catalan multiple system atrophy-registry (CMSAR)
author_role author
author2 Arnal, Magdalena
Botta Orfila, Teresa
Giraldo, Darly
Fernández, Manel
Compta, Yaroslau
Fernández-Santiago, Ruben
Ezquerra, Mario
Tartaglia, Gian Gaetano
Martí, M. Josep
Catalan multiple system atrophy-registry (CMSAR)
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Computational biology and bioinformatics
Movement disorders
Neurological disorders
Neurology
Neuroscience
topic Computational biology and bioinformatics
Movement disorders
Neurological disorders
Neurology
Neuroscience
description Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
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info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45499
http://dx.doi.org/10.1038/s41598-020-66221-4
url http://hdl.handle.net/10230/45499
http://dx.doi.org/10.1038/s41598-020-66221-4
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sci Rep. 2020; 10(1):10310
info:eu-repo/grantAgreement/EC/FP7/309545
info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-P
info:eu-repo/grantAgreement/ES/1PE/SAF2015-73508-JIN
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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spelling Transcriptomic differences in MSA clinical variantsPérez Soriano, AlexandraArnal, MagdalenaBotta Orfila, TeresaGiraldo, DarlyFernández, ManelCompta, YaroslauFernández-Santiago, RubenEzquerra, MarioTartaglia, Gian GaetanoMartí, M. JosepCatalan multiple system atrophy-registry (CMSAR)Computational biology and bioinformaticsMovement disordersNeurological disordersNeurologyNeuroscienceBackground: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.We would like to thank all the patients for their always willing and generous collaboration. This project has been possible thanks to the funding from the Fundació Marató TV3 and CERCA Programme from Generalitat de Catalunya. We also thank the European Research Council RIBOMYLOME_309545 and Spanish Ministry of Economy and Competitiveness (BFU2017-86970-P). A.P.-S. was funded by a PHD4MD grant, which is a collaborative research training program for medical doctors. R.F.-S. was supported by a Jóvenes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigación (AEI) (AEI/FEDER/UE) (grant # SAF2015-73508-JIN), and a Miguel Servet grant from the Instituto de Salud Carlos III (grant # CP19/00048). M.F. was funded by María de Maeztu programme (grant # MDM-2017-0729). Thanks to Lara Nonell, head of the Human Computational Biology group in IMIM, for offering the computational resources in the institution and the help with data management.Nature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45499http://dx.doi.org/10.1038/s41598-020-66221-4reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésSci Rep. 2020; 10(1):10310info:eu-repo/grantAgreement/EC/FP7/309545info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-Pinfo:eu-repo/grantAgreement/ES/1PE/SAF2015-73508-JIN© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/454992026-06-12T07:21:37Z
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