Akademik Veri Yönetim Sistemi
Tez Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Muğla Sıtkı Koçman Üniversitesi, Fen Bilimleri Enstitüsü, Biyoinformatik (Tezli), Türkiye
Tez Danışmanı: Ömür Baysal
Tezin Onay Tarihi: 2019
Tezin Dili: İngilizce
Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
Özet:
Neurodegenerative diseases are characterized as the progressive loss of neural cells, e.g. neurons and glial cells, within disease-specific regions and/or tissues. While many individual genes, such as APP for Alzheimer disease, and biological pathways are studied for neurodegenerative diseases, system-wide pathogenesis could not be revealed; thus, we are far from effective treatment strategies. High throughput sequencing studies, especially RNA Sequencing (RNA-Seq), have delivered promising results in recent years, confirming findings of standard experimental studies. Moreover, the public availability of the RNA-Seq data made it possible to re- analyse many of them in parallel, namely meta-analysis. Meta-analysis is proven to be a good assessment tool in the field as it helps to minimize the batch effect derived differences and to identify similarly altered factors among studies.
In this thesis, a meta-analysis of RNA-Seq studies was carried out for three neurodegenerative diseases, namely Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS). For this purpose, publicly available Alzheimer’s disease, Parkinson’s disease and ALS disease RNA-Seq datasets from Sequence Read Archive (SRA) database. The significantly differentially expressed genes common to these studies were first identified and looked for disease-associated pathways and variations.
A meta-analysis conducted in this thesis further validated the importance of genes in heat shock proteins (HSPs) associated pathways and GABA synthesis pathways. The downregulated genes linked to GABA synthesis (e.g. GAD1 and GAD2), the upregulated genes related to the cellular response to heat stress (e.g. DNAJB6 and HSP90AA1), also contain variations. The significance of genes and pathways identified corroborated by the recent literature on neurodegenerative diseases.