META-ANALYSIS OF GENE EXPRESSION HETEROGENEITY IN BRAIN DEVELOPMENT AND AGING

Download

thesis.pdf

Date

2022-9-1

Author

Işıldak, Ulaş

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

242
views

201
downloads

Aging is a complex process associated with the accumulation of stochastic genetic and epigenetic alterations, leading to functional decline and increased risk for disease and death. Although some previous studies demonstrated a tendency towards increased inter-individual heterogeneity during aging, whether it is a function of time that starts at the beginning of life is unknown. Its functional consequences and regulations have also not been systematically studied. In this study, I addressed these questions by the meta-analysis of 19 microarray age-series datasets, comprising 17 brain regions of 298 individuals. Investigating the age-related gene expression heterogeneity changes, I found that there is a significant shift towards increased heterogeneity consistency during aging (20 to 98 years of age) compared to the post-natal development period (0 to 20 years of age). Moreover, the genes that become more heterogeneous consistently across all aging datasets were found to be associated with biological processes and pathways that are related to neuronal function (i.e., axon guidance, postsynaptic specialization) and longevity (i.e., autophagy, mTOR signaling). Gene set enrichment analysis for transcriptional regulators (i.e., miRNAs and transcription factors) further revealed a positive correlation between the number of regulators and consistent changes in heterogeneity, indicating the possible role of transcriptional regulators in the underlying mechanism. Overall, the results presented here demonstrate that increased inter-individual expression heterogeneity is a general characteristic of the aging human brain, which is associated with multiple lifespans and disease-related pathways and processes, suggesting that increased heterogeneity may contribute to the emergence of aging-associated phenotypes.

Subject Keywords

aging, development, gene expression, heterogeneity, brain

URI

https://hdl.handle.net/11511/99569

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Meta analysis of alzheimer’s disease at the gene expression level İzgi, Hamit; Somel, Mehmet; Department of Biology (2017) In this study, publicly available microarray gene expression datasets are used to investigate common gene expression changes in different postmortem brain regions in Alzheimer’s Disease (AD) patients compared to control subjects, and to find possible functional associations related to these changes. The hypothesis is that pathogenesis of the disease converges into common patterns of dysregulation/alteration or dysfunction in molecular pathways across different brain regions in AD. In total, I studied 13 dat...
Molecular footprint of Medawar's mutation accumulation process in mammalian aging Turan, Zeliha Gozde; Parvizi, Poorya; Donertas, Handan Melike; Tung, Jenny; Khaitovich, Philipp; Somel, Mehmet (2019-08-01) Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging-related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults...
Notable decrease in transcriptome conservation during mammalian aging Turan, Zeliha Gözde; Somel, Mehmet; Department of Biology (2016) Aging is a complex process that causes decline in organisms’ reproductive capacity and chance of survival. Even though aging tends to reduce fitness, it is not eliminated by natural selection and is observed in many multicellular species, and this leads to an evolutionary paradox. The mutation accumulation theory states that due to the declining force of natural selection with age, old-age-expressed deleterious mutations will not be effectively eliminated, and can contribute to the aging phenotype. A limite...
Meta-analysis of gene expression reversals in ageing brain Dönertaş, Handan Melike; Somel, Mehmet; Department of Biology (2016) Brain ageing is characterised by disruptive changes in cognitive abilities, histology, and anatomy. The underlying molecular nature of brain ageing, on the other hand, is little understood, partly due to the stochastic and heterogeneous nature of ageing process. In this study, using published microarray studies spanning 22 brain regions with 1,015 samples, gene expression changes in ageing are analysed in comparison to those in postnatal development. A previous observation that mRNA abundance of a large num...
Clustering of short time-course gene expression data with dissimilar replicates Cinar, Ozan; İlk Dağ, Özlem; İyigün, Cem (2018-04-01) Microarrays are used in genetics and medicine to examine large numbers of genes simultaneously through their expression levels under any condition such as a disease of interest. The information from these experiments can be enriched by following the expression levels through time and biological replicates. The purpose of this study is to propose an algorithm which clusters the genes with respect to the similarities between their behaviors through time. The algorithm is also aimed at highlighting the genes w...

Citation Formats

U. Işıldak, “META-ANALYSIS OF GENE EXPRESSION HETEROGENEITY IN BRAIN DEVELOPMENT AND AGING,” M.S. - Master of Science, Middle East Technical University, 2022.