Alzheimer hastalığının gen anlatımı düzeyinde meta analizi.

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 datasets, one of which was excluded from the analysis in quality checks, resulting in 12 datasets spanning 7 different brain regions. Instead of using the standard approach to identify differentially expressed genes in each dataset independently, I used an alternative scheme, focusing on shared trends across all datasets, and testing their significance using cross-dataset structured permutations. Among more than 8000 common genes in all 12 datasets, I identified those showing shared upregulated (631) or downregulation (580) trends in AD across all datasets, which was highly significant compared to permutations. I then performed GO Biological Process enrichment analysis on both gene sets. There were 343 GO BP categories enriched for upregulated genes and 94 GO BP categories enriched for downregulated genes. Among 343 GO categories enriched for upregulated genes, the most noticeable ones include protein modification, differentiation, and the cell cycle. Furthermore, cell-cell signaling, synaptic activity and energy metabolism related pathways are enriched in downregulated genes. These findings are in line with the effects of pathological changes in AD and suggests that different brain regions share common pathways deregulated by AD.M.S. - Master of Scienc

FEN BİLİMLERİ ENSTİTÜSÜ/LİSANSÜSTÜ TEZ PROJESİ

ÖSTROJEN YANITLI CXXC5 GENİNİN TRANSKRİPSİYONEL OLARAK DÜZENLENMES

Yeni nesil moleküler veri analizi yoluyla genom ve transkriptom evriminin incelenmesi

Tüm genom dizileme verisi, genom çapında veya ekzom çapında polimorfizm verisi, mikrodizin ve RNA-dizileme verisi, GC-MS metabolit verisi gibi geniş çaplı moleküler veri setlerinin hesaplamalı analizi yoluyla uzun zamandır biyologları meşgul eden çok sayıda sorunun cevaplanması bugün mümkün hale gelmiştir. Araştırma grubumuzda genom ve transkriptom evrimi üzerine şu soruları gelecek yıl içinde cevaplayamaya çalışacağız:- Primatlar arasında testis transkriptomu niye ve nasıl evrilmektedir? - Türler arasında transkriptom farkları arasında en anlamlı olanlar nasıl tespit edilir?- Genom çapında kısa nükleotit homopolimerleri oluşturan mutasyonların insan popülasyonu içinde hızlı yayılmasının sebepleri nelerdir? - Yaşlanma sırasında metabolit ve gen ifadesi değişimlerinin sebepleri nedir?- Anadolu insan popülasyonunda Neandertal karışımı başka popülasyonlardan farklı olabilir mi?- Anadolu’da geçmiş göç örüntüleri nelerdir?- Mesane kanserinde görülen senkronize tümörler akraba mıdır

Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity

Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver, and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we term Divergence followed by Convergence (DiCo). We found that DiCo was most prevalent among tissue-specific genes and associated with loss of tissue identity, which is confirmed using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell-type composition and also by cell-autonomous expression changes within particular cell types