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Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma

PURPOSE: Performing bioinformatics analyses using trabecular meshwork (TM) gene expression data in order to further elucidate the molecular pathogenesis of primary open‐angle glaucoma (POAG), and to identify candidate target genes. METHODS: A systematic search in Gene Expression Omnibus and ArrayExp...

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Autores principales: Liesenborghs, Ilona, Eijssen, Lars M. T., Kutmon, Martina, Gorgels, Theo G. M. F., Evelo, Chris T., Beckers, Henny J. M., Webers, Carroll A. B., Schouten, Johannes S. A. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004120/
https://www.ncbi.nlm.nih.gov/pubmed/31197946
http://dx.doi.org/10.1111/aos.14154
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author Liesenborghs, Ilona
Eijssen, Lars M. T.
Kutmon, Martina
Gorgels, Theo G. M. F.
Evelo, Chris T.
Beckers, Henny J. M.
Webers, Carroll A. B.
Schouten, Johannes S. A. G.
author_facet Liesenborghs, Ilona
Eijssen, Lars M. T.
Kutmon, Martina
Gorgels, Theo G. M. F.
Evelo, Chris T.
Beckers, Henny J. M.
Webers, Carroll A. B.
Schouten, Johannes S. A. G.
author_sort Liesenborghs, Ilona
collection PubMed
description PURPOSE: Performing bioinformatics analyses using trabecular meshwork (TM) gene expression data in order to further elucidate the molecular pathogenesis of primary open‐angle glaucoma (POAG), and to identify candidate target genes. METHODS: A systematic search in Gene Expression Omnibus and ArrayExpress was conducted, and quality control and preprocessing of the data was performed with ArrayAnalysis.org. Molecular pathway overrepresentation analysis was performed with PathVisio using pathway content from three pathway databases: WikiPathways, KEGG and Reactome. In addition, Gene Ontology (GO) analysis was performed on the gene expression data. The significantly changed pathways were clustered into functional categories which were combined into a network of connected genes. RESULTS: Ninety‐two significantly changed pathways were clustered into five functional categories: extracellular matrix (ECM), inflammation, complement activation, senescence and Rho GTPase signalling. ECM included pathways involved in collagen, actin and cell–matrix interactions. Inflammation included pathways entailing NF‐κB and arachidonic acid. The network analysis showed that several genes overlap between the inflammation cluster on the one hand, and the ECM, complement activation and senescence clusters on the other hand. GO analysis, identified additional clusters, related to development and corticosteroids. CONCLUSION: This study provides an overview of the processes involved in the molecular pathogenesis of POAG in the TM. The results show good face validity and confirm findings from histological, biochemical, genome‐wide association and transcriptomics studies. The identification of known points of action for drugs, such as Rho GTPase, arachidonic acid, NF‐κB, prostaglandins and corticosteroid clusters, supports the value of this approach to identify potential drug targets.
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spelling pubmed-70041202020-02-11 Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma Liesenborghs, Ilona Eijssen, Lars M. T. Kutmon, Martina Gorgels, Theo G. M. F. Evelo, Chris T. Beckers, Henny J. M. Webers, Carroll A. B. Schouten, Johannes S. A. G. Acta Ophthalmol Original Articles PURPOSE: Performing bioinformatics analyses using trabecular meshwork (TM) gene expression data in order to further elucidate the molecular pathogenesis of primary open‐angle glaucoma (POAG), and to identify candidate target genes. METHODS: A systematic search in Gene Expression Omnibus and ArrayExpress was conducted, and quality control and preprocessing of the data was performed with ArrayAnalysis.org. Molecular pathway overrepresentation analysis was performed with PathVisio using pathway content from three pathway databases: WikiPathways, KEGG and Reactome. In addition, Gene Ontology (GO) analysis was performed on the gene expression data. The significantly changed pathways were clustered into functional categories which were combined into a network of connected genes. RESULTS: Ninety‐two significantly changed pathways were clustered into five functional categories: extracellular matrix (ECM), inflammation, complement activation, senescence and Rho GTPase signalling. ECM included pathways involved in collagen, actin and cell–matrix interactions. Inflammation included pathways entailing NF‐κB and arachidonic acid. The network analysis showed that several genes overlap between the inflammation cluster on the one hand, and the ECM, complement activation and senescence clusters on the other hand. GO analysis, identified additional clusters, related to development and corticosteroids. CONCLUSION: This study provides an overview of the processes involved in the molecular pathogenesis of POAG in the TM. The results show good face validity and confirm findings from histological, biochemical, genome‐wide association and transcriptomics studies. The identification of known points of action for drugs, such as Rho GTPase, arachidonic acid, NF‐κB, prostaglandins and corticosteroid clusters, supports the value of this approach to identify potential drug targets. John Wiley and Sons Inc. 2019-06-14 2020-02 /pmc/articles/PMC7004120/ /pubmed/31197946 http://dx.doi.org/10.1111/aos.14154 Text en © 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Liesenborghs, Ilona
Eijssen, Lars M. T.
Kutmon, Martina
Gorgels, Theo G. M. F.
Evelo, Chris T.
Beckers, Henny J. M.
Webers, Carroll A. B.
Schouten, Johannes S. A. G.
Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title_full Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title_fullStr Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title_full_unstemmed Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title_short Comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
title_sort comprehensive bioinformatics analysis of trabecular meshwork gene expression data to unravel the molecular pathogenesis of primary open‐angle glaucoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004120/
https://www.ncbi.nlm.nih.gov/pubmed/31197946
http://dx.doi.org/10.1111/aos.14154
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