Exploring the chromatin landscape and gene expression mechanisms

Programa de Doctorat en Biomedicina / Tesi realitzada a l'Instut de Recerca Biomèdica (IRB Barcelona)

Detalles Bibliográficos
Autor: Sala Huerta, Alba
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/693602
Acceso en línea:http://hdl.handle.net/10803/693602
Access Level:acceso abierto
Palabra clave:Cromatina
Chromatin
Regulació genètica
Regulación genética
Genetic regulation
Aprenentatge automàtic
Aprendizaje automático
Machine learning
Ciències Experimentals i Matemàtiques
577
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Exploring the chromatin landscape and gene expression mechanisms
title Exploring the chromatin landscape and gene expression mechanisms
spellingShingle Exploring the chromatin landscape and gene expression mechanisms
Sala Huerta, Alba
Cromatina
Chromatin
Regulació genètica
Regulación genética
Genetic regulation
Aprenentatge automàtic
Aprendizaje automático
Machine learning
Ciències Experimentals i Matemàtiques
577
title_short Exploring the chromatin landscape and gene expression mechanisms
title_full Exploring the chromatin landscape and gene expression mechanisms
title_fullStr Exploring the chromatin landscape and gene expression mechanisms
title_full_unstemmed Exploring the chromatin landscape and gene expression mechanisms
title_sort Exploring the chromatin landscape and gene expression mechanisms
dc.creator.none.fl_str_mv Sala Huerta, Alba
author Sala Huerta, Alba
author_facet Sala Huerta, Alba
author_role author
dc.contributor.none.fl_str_mv Orozco López, Modesto
Battistini, Federica
Orozco López, Modesto
Universitat de Barcelona. Facultat de Biologia
dc.subject.none.fl_str_mv Cromatina
Chromatin
Regulació genètica
Regulación genética
Genetic regulation
Aprenentatge automàtic
Aprendizaje automático
Machine learning
Ciències Experimentals i Matemàtiques
577
topic Cromatina
Chromatin
Regulació genètica
Regulación genética
Genetic regulation
Aprenentatge automàtic
Aprendizaje automático
Machine learning
Ciències Experimentals i Matemàtiques
577
description Programa de Doctorat en Biomedicina / Tesi realitzada a l'Instut de Recerca Biomèdica (IRB Barcelona)
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/693602
url http://hdl.handle.net/10803/693602
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 321 p.
application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405364567408640
spelling Exploring the chromatin landscape and gene expression mechanismsSala Huerta, AlbaCromatinaChromatinRegulació genèticaRegulación genéticaGenetic regulationAprenentatge automàticAprendizaje automáticoMachine learningCiències Experimentals i Matemàtiques577Programa de Doctorat en Biomedicina / Tesi realitzada a l'Instut de Recerca Biomèdica (IRB Barcelona)[eng] The interplay between chromatin, transcription factors and genes defines a complex gene regulatory system whose study is essential to understand cell differentiation and how relevant cell functions are maintained or disrupted during biological processes. This is the main area of interest of what is known as 4D genomics, a field that has been evolving on the wave of high-throughput methods producing extensive amounts of data on gene location, chromatin structure and gene expression. 4D genomics data is each day more accessible, the challenge being to interpret it. In this sense Machine Learning (ML) and Artificial Intelligence (AI) methods are becoming crucial to transform noisy experimental data into biological information. The aim of this thesis is to untangle some of the mechanisms that constitute regulatory networks while integrating various state-of-the-art techniques to further understand some of the currently unanswered challenges. During my PhD thesis I have been exploring the chromatin landscape and gene expression mechanisms at different levels of detail and this volume summarizes the main results obtained. In the Introduction, a brief overview of gene expression and transcriptional regulation mechanisms is provided. I also discuss the underpinnings of chromatin organization and stress conditions. Chapters 1 through 5 are a compendium of articles where I describe the different research projects that I undertook during my PhD thesis. These projects have either been published in peer-review journals, are currently under review or in preparation. More specifically in Chapter 1 we started by studying the first regulatory layer, the double-stranded helical structure of DNA and its binding to effector proteins. We developed a ML model that predicted with high accuracy the in vitro affinities and binding sites of various transcription factors based on physical properties of the DNA. Our method also successfully reproduced in vivo data when combined with a second layer of information, the chromatin organization of the nucleosomes. In Chapter 2 we explored nucleosome positioning preferences in yeast genomic DNA by first developing a predictor of nucleosome free regions around the transcription start and terminating sites which are known to comprise critical binding sites. Our method allowed us to predict the nucleosome architecture within gene bodies by using signal theory from two strongly positioned nucleosomes referred to as +1 and -last (the nucleosomes immediately downstream of the TSS or upstream of the TTS respectively). We additionally studied the link between nucleosome arrangements and gene expression mechanisms. In Chapter 3, the effects of oxidative stress damage on nucleosome organization and overall chromatin structure are described. In order to clarify the effect of these lesions, we performed statistical analysis on a series of gene expression mechanisms through different experimental techniques such as MNase-Seq, Hi-C and Micro-C experiments. Chapters 4 and 5 introduce the study of RNA as a distinct structure and discuss its properties and capability of playing a key role in some regulatory mechanisms such as triplex forming oligonucleotides. A general discussion that encompasses the significance and future perspectives of these 5 projects is presented in Chapter 6, together with the main conclusions of this work in Chapter 7.Universitat de BarcelonaOrozco López, ModestoBattistini, FedericaOrozco López, ModestoUniversitat de Barcelona. Facultat de Biologia202520252024info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion321 p.application/pdfhttp://hdl.handle.net/10803/693602TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6936022026-06-14T12:46:07Z
score 15,812429

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