Identification and characterization of non-coding genomic variations associated to cancer diseases

[eng] The genetic and molecular bases of most of the human diseases have become one of the main goals of the human biology in the last decades. To be able to unveil the genetic variations and the affected cellular processes associated with a specific disease is crucial in order to generate accurate...

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Detalhes bibliográficos
Autor: González Rosado, Santiago
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/104087
Acesso em linha:https://hdl.handle.net/2445/104087
http://hdl.handle.net/10803/397789
Access Level:acceso abierto
Palavra-chave:Genòmica
Càncer
Genomics
Cancer
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oai_identifier_str oai:diposit.ub.edu:2445/104087
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Identification and characterization of non-coding genomic variations associated to cancer diseases
title Identification and characterization of non-coding genomic variations associated to cancer diseases
spellingShingle Identification and characterization of non-coding genomic variations associated to cancer diseases
González Rosado, Santiago
Genòmica
Càncer
Genomics
Cancer
title_short Identification and characterization of non-coding genomic variations associated to cancer diseases
title_full Identification and characterization of non-coding genomic variations associated to cancer diseases
title_fullStr Identification and characterization of non-coding genomic variations associated to cancer diseases
title_full_unstemmed Identification and characterization of non-coding genomic variations associated to cancer diseases
title_sort Identification and characterization of non-coding genomic variations associated to cancer diseases
dc.creator.none.fl_str_mv González Rosado, Santiago
author González Rosado, Santiago
author_facet González Rosado, Santiago
author_role author
dc.contributor.none.fl_str_mv Torrents Arenales, David
Gelpí Buchaca, Josep Lluís
Universitat de Barcelona. Facultat de Biologia
dc.subject.none.fl_str_mv Genòmica
Càncer
Genomics
Cancer
topic Genòmica
Càncer
Genomics
Cancer
description [eng] The genetic and molecular bases of most of the human diseases have become one of the main goals of the human biology in the last decades. To be able to unveil the genetic variations and the affected cellular processes associated with a specific disease is crucial in order to generate accurate diagnosis and further therapies. The Next Generation Sequencing (NGS) revolution, with the associated reduction in time and costs of sequencing, has allowed the scientist to access large number of human genomes to their biomedical studies. The study of genetic disorders, cancer in particular, has benefit from NGS identifying genetic variations associated with a given disorder. All these new results, some of them in regions with unknown function, have generated a double challenge in the scientific community. Firstly, detect as much as possible all the different variants associated with a disease, in some complex diseases several. Secondly, to understand the functional impact those modifications are causing in the cell. Regarding the first challenge, this thesis contributes in the identification of genetic modifications throw the development of a bioinformatics tool named SMUFIN (Moncunill et al. 2014). SMUFIN can detect somatic variants related with tumour development and progression in a quickly and effective way. Not limited to the software development, several tumours has been analysed and their somatic variants characterized. These tumours include mantel cell lymphoma, paediatric medulloblastoma and chronic lymphocytic leukaemia (Moncunill et al. 2014; Puente et al. 2015). In the evaluation of the functional impact, the thesis also includes a method, RELA, to determine when these annotated variants play a regulatory role as enhancers or promoters (Gonzalez et al. 2012). Combined with other available data and a spread methodology to unveil regulatory regions evaluation of variants affecting regulatory regions have been performed in chronic lymphocytic leukaemia (details included in the thesis discussion). To sum up, this thesis cover with methodology and provide bioinformatics tools to perform a complete genomic analysis of genetic variants in biomedicine studies. It includes from the identification of variants for each of the patients to the evaluation of their functional impact in the disease development and progression. This kind of approach is currently common in the research laboratories and it will be part of the healthcare system in a close future to diagnose and classify patients.
publishDate 2016
dc.date.none.fl_str_mv 2016
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 https://hdl.handle.net/2445/104087
http://hdl.handle.net/10803/397789
url https://hdl.handle.net/2445/104087
http://hdl.handle.net/10803/397789
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc-by (c) González, 2016
http://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) González, 2016
http://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 Tesis Doctorals - Facultat - Biologia
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Identification and characterization of non-coding genomic variations associated to cancer diseasesGonzález Rosado, SantiagoGenòmicaCàncerGenomicsCancer[eng] The genetic and molecular bases of most of the human diseases have become one of the main goals of the human biology in the last decades. To be able to unveil the genetic variations and the affected cellular processes associated with a specific disease is crucial in order to generate accurate diagnosis and further therapies. The Next Generation Sequencing (NGS) revolution, with the associated reduction in time and costs of sequencing, has allowed the scientist to access large number of human genomes to their biomedical studies. The study of genetic disorders, cancer in particular, has benefit from NGS identifying genetic variations associated with a given disorder. All these new results, some of them in regions with unknown function, have generated a double challenge in the scientific community. Firstly, detect as much as possible all the different variants associated with a disease, in some complex diseases several. Secondly, to understand the functional impact those modifications are causing in the cell. Regarding the first challenge, this thesis contributes in the identification of genetic modifications throw the development of a bioinformatics tool named SMUFIN (Moncunill et al. 2014). SMUFIN can detect somatic variants related with tumour development and progression in a quickly and effective way. Not limited to the software development, several tumours has been analysed and their somatic variants characterized. These tumours include mantel cell lymphoma, paediatric medulloblastoma and chronic lymphocytic leukaemia (Moncunill et al. 2014; Puente et al. 2015). In the evaluation of the functional impact, the thesis also includes a method, RELA, to determine when these annotated variants play a regulatory role as enhancers or promoters (Gonzalez et al. 2012). Combined with other available data and a spread methodology to unveil regulatory regions evaluation of variants affecting regulatory regions have been performed in chronic lymphocytic leukaemia (details included in the thesis discussion). To sum up, this thesis cover with methodology and provide bioinformatics tools to perform a complete genomic analysis of genetic variants in biomedicine studies. It includes from the identification of variants for each of the patients to the evaluation of their functional impact in the disease development and progression. This kind of approach is currently common in the research laboratories and it will be part of the healthcare system in a close future to diagnose and classify patients.[spa] El estudio de las bases genéticas y moleculares de las patologías humanas ha constituido el centro de atención de gran parte de la investigación en biología durante las últimas décadas con el fin último de comprender los procesos celulares alterados en cada caso y la posibilidad de generar protocolos de diagnosis y terapias específicas. Con la llegada de la denominada Next Generation Sequencing (NGS) y su consiguiente reducción en tiempo y costes ha permitido el acceso a la secuenciación de numeroso genomas humanos en el entorno biomédico. El estudio de enfermedades genéticas, y del cáncer en particular, se ha visto enormemente favorecido al poder incorporar un importante número de genomas de pacientes a sus estudios y así poder identificar directamente las mutaciones asociadas a cada patología. A su vez, esta revolución junto con la capacidad de detectar modificaciones genéticas en regiones cuya función todavía se desconoce, ha generado un doble desafío en la comunidad científica: por un lado el análisis de variantes genéticas asociadas a cada tipo de enfermedad y, por el otro, el entender el impacto funcional que dichas modificaciones provocan en la célula. Esta tesis contribuye a solucionar estas limitaciones a través del desarrollo de una aplicación, SMUFIN (Moncunill et al. 2014), que permite de forma rápida y eficaz la identificación de variaciones somáticas asociadas al desarrollo o progresión de tumores. También se describen los resultados obtenidos relativos a la identificación y caracterización de las reorganizaciones cromosómicas en cáncer, así como los resultados obtenido en cuanto a sus mecanismos e impacto funcional (Puente et al. 2015). Además, como parte de la anotación genómica para la interpretación funcional de las variaciones detectadas, esta tesis incluye los resultados del desarrollo de estrategias y metodologías para la detección de regiones reguladoras en genomas de eucariotas (Gonzalez et al. 2012). En resumen esta tesis intenta cubrir y dotar de herramientas bionformáticas para completar los pasos necesarios para el análisis de genomas en biomedicina, desde que un grupo de pacientes son secuenciados hasta que sus diferentes variantes son identificadas y su impacto funcional determinado. Este tipo de análisis, que ahora esta ocurriendo en el campo de la investigación, pronto será una realidad y una rutina en el sistema sanitario.Universitat de BarcelonaTorrents Arenales, DavidGelpí Buchaca, Josep LluísUniversitat de Barcelona. Facultat de Biologia2016info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/104087http://hdl.handle.net/10803/397789Tesis Doctorals - Facultat - Biologiareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc-by (c) González, 2016http://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1040872026-05-27T06:46:51Z
score 15.300719

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