A systematically derived overview of the non-ubiquitous pathways and genes that define the molecular and genetic signature of the healthy trabecular meshwork.

Autor: Liesenborghs I; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands; Maastricht Centre of Systems Biology (MaCSBio), Maastricht University, the Netherlands. Electronic address: ilona.liesenborghs@mumc.nl., Schouten JSAG; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands; Department of Ophthalmology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands., Kutmon M; Maastricht Centre of Systems Biology (MaCSBio), Maastricht University, the Netherlands; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, the Netherlands., Gorgels TGMF; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands., Evelo CT; Maastricht Centre of Systems Biology (MaCSBio), Maastricht University, the Netherlands; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, the Netherlands., Hubens WHG; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, the Netherlands., Beckers HJM; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands., Webers CAB; University Eye Clinic Maastricht, Maastricht University Medical Center+, the Netherlands., Eijssen LMT; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, the Netherlands; School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, the Netherlands.
Jazyk: angličtina
Zdroj: Genomics [Genomics] 2022 Mar; Vol. 114 (2), pp. 110280. Date of Electronic Publication: 2022 Feb 04.
DOI: 10.1016/j.ygeno.2022.110280
Abstrakt: Purpose: The trabecular meshwork (TM) is situated in the most frontal part of the eye and is thought to play an important role in the regulation of the eye pressure. However, this tissue is rather difficult to harvest for research. The purpose of this study is therefore to integrate the existing gene expression data of the healthy TM to increase sample size and identify its signature genes and pathways. This provides a robust reference for the study of molecular disease processes and supports the selection of candidate target genes for new treatments.
Methods: A systematic search identified microarray data of healthy TM tissue. After quality control, datasets of low quality and deviating samples were excluded. Remaining individuals were jointly normalized and integrated into one database. The average gene expression of each tested gene over all individuals was calculated. The 25% genes with the highest average expression were identified as the most active genes in the healthy TM and used as input for pathway and network analysis. Additionally, ubiquitous pathways and genes were identified and excluded from the results. Lastly, we identified genes which are likely to be TM-specific.
Results: The gene expression data of 44 individuals, obtained from 18 datasets, were jointly normalized. Ubiquitous genes (n = 688) and ubiquitous pathways (n = 73) were identified and excluded. Following, 1882 genes and 211 pathways were identified as the signature genes and pathways of the healthy TM. Pathway analysis revealed multiple molecular processes of which some were already known to be active in the TM, for example extracellular matrix and elastic fiber formation. Forty-six candidate TM-specific genes were identified. These consist mainly of pseudogenes or novel transcripts of which the function is unknown.
Conclusions: In this comprehensive meta-analysis we identified non-ubiquitous genes and pathways that form the signature of the functioning of the healthy TM. Additionally, 46 candidate TM-specific genes were identified. This method can also be used for other tissues that are difficult to obtain for study.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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