A carregar...
Publicação
The dark side of the genome: Development of a computational pipeline to identify transposable elements with a functional role in genome regulation
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 4.93 MB | Adobe PDF |
Autores
Resumo(s)
Transposable elements (TEs), which constitute nearly half of the human genome, have historically been
viewed as parasitic sequences with little functional importance. However, growing evidence suggests
that TEs play pivotal roles in gene expression and epigenetic modulation. This thesis aims to develop
and implement a computational pipeline to explore the functional roles of TEs in gene regulation using
human embryonic stem cells (hESCs), as a model system known for its relevance to early development
and cellular therapies.
The methodology involves the analysis of total RNA sequencing (RNA-seq) datasets from both primed
and naive hESCs, two distinct pluripotency states, which have been shown to have a remarkably distinct
pattern of TE transcription. The pipeline includes preprocessing, alignment, and quantification of gene
and TE expression using custom TE annotations. Differential expression analysis was performed at both
the TE subfamily and individual loci levels to identify TEs that are differentially active in a given state
and that could be important for its transcriptional regulation. Additionally, we applied statistical tests to
assess the genomic association between differentially expressed TEs and differentially expressed genes.
Our analysis identified key TE subfamilies, including endogenous retroviruses (ERVs), Alus, SINEVNTR-Alus (SVAs), and LINE elements, that are differentially expressed between naive and primed
states of hESCs. Moreover, genomic proximity analysis revealed a potential regulatory relationship
between these TEs and neighbouring genes, suggesting that TEs may serve as cis-regulatory elements
contributing to cell state-specific gene expression profiles.
In conclusion, this work establishes a robust pipeline for the parallel analysis of gene and TE expression,
providing new insights into the potential regulatory roles of TEs in hESCs. Future studies could apply
this pipeline to other developmental systems or disease models, offering a broader understanding of TEmediated regulation and its implications for genome function in health and disease.
Descrição
Tese de mestrado, Bioinformática e Biologia Computacional, 2025, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
elementos de transposição sequenciação de RNA transcriptómica computacional células estaminais embrionárias humanas Teses de mestrado - 2025