Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis
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Le résumé fourni par la source
The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis
- Date Crossref
- 09/01/2015
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Leicester Department of Cell Physiology and Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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University of Bonn Institute of Reconstructive Neurobiology pays non établi dans la noticeUniversité ou école supérieure
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The University of Queensland Queensland Brain Institute pays non établi dans la noticeUniversité ou école supérieure
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Park Centre for Mental Health pays non établi dans la noticeÉtablissement de santé
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Berlin-Brandenburger Centrum für Regenerative Therapien pays non établi dans la noticeStructure de recherche
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Center for Regenerative Therapies Dresden pays non établi dans la noticeStructure de recherche
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Florey Institute of Neuroscience and Mental Health pays non établi dans la noticeStructure de recherche
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The Bioinformatics Core and The Synaptic Neurobiology Laboratory pays non établi dans la noticeStructure de recherche
Department of Cell Physiology and Pharmacology — University of Leicester, Institute of Reconstructive Neurobiology — University of Bonn et Queensland Brain Institute — The University of Queensland, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.