Detection and classification of somatic structural variants, and its application in the study of neuronal development

Tesi realitzada al Centre de Supercomputació de Barcelona (BSC) / Programa de Doctorat en Biomedicina

Bibliographic Details
Author: Planas Fèlix, Mercè
Format: doctoral thesis
Status:Published version
Publication Date:2020
Country:España
Institution:CBUC, CESCA
Repository:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/672163
Online Access:http://hdl.handle.net/10803/672163
Access Level:Open access
Keyword:Càncer
Cáncer
Cancer
Genètica humana
Genética humana
Human genetics
Bioinformàtica
Bioinformática
Bioinformatics
Genòmica
Genómica
Genomics
Ciències Experimentals i Matemàtiques
575
id ES_8e4b00986717cc2dbb06ca460dcd82a6
oai_identifier_str oai:www.tdx.cat:10803/672163
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Detection and classification of somatic structural variants, and its application in the study of neuronal development
title Detection and classification of somatic structural variants, and its application in the study of neuronal development
spellingShingle Detection and classification of somatic structural variants, and its application in the study of neuronal development
Planas Fèlix, Mercè
Càncer
Cáncer
Cancer
Genètica humana
Genética humana
Human genetics
Bioinformàtica
Bioinformática
Bioinformatics
Genòmica
Genómica
Genomics
Ciències Experimentals i Matemàtiques
575
title_short Detection and classification of somatic structural variants, and its application in the study of neuronal development
title_full Detection and classification of somatic structural variants, and its application in the study of neuronal development
title_fullStr Detection and classification of somatic structural variants, and its application in the study of neuronal development
title_full_unstemmed Detection and classification of somatic structural variants, and its application in the study of neuronal development
title_sort Detection and classification of somatic structural variants, and its application in the study of neuronal development
dc.creator.none.fl_str_mv Planas Fèlix, Mercè
author Planas Fèlix, Mercè
author_facet Planas Fèlix, Mercè
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 Càncer
Cáncer
Cancer
Genètica humana
Genética humana
Human genetics
Bioinformàtica
Bioinformática
Bioinformatics
Genòmica
Genómica
Genomics
Ciències Experimentals i Matemàtiques
575
topic Càncer
Cáncer
Cancer
Genètica humana
Genética humana
Human genetics
Bioinformàtica
Bioinformática
Bioinformatics
Genòmica
Genómica
Genomics
Ciències Experimentals i Matemàtiques
575
description Tesi realitzada al Centre de Supercomputació de Barcelona (BSC) / Programa de Doctorat en Biomedicina
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
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/10803/672163
url http://hdl.handle.net/10803/672163
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 277 p.
application/pdf
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_ 1869413117002252288
spelling Detection and classification of somatic structural variants, and its application in the study of neuronal developmentPlanas Fèlix, MercèCàncerCáncerCancerGenètica humanaGenética humanaHuman geneticsBioinformàticaBioinformáticaBioinformaticsGenòmicaGenómicaGenomicsCiències Experimentals i Matemàtiques575Tesi realitzada al Centre de Supercomputació de Barcelona (BSC) / Programa de Doctorat en BiomedicinaThe identification and analysis of genomic variation across individuals has been central in biology, first through comparative genomics to answer evolutionary questions, and then in the context of biomedicine, where it is actually becoming central to the study of most diseases. Next generation sequence technologies are allowing the systematic analysis of thousands of different types of genetic variation, enhancing the identification of disease markers and the understanding of the molecular basis of disease. For the past years, there has been a burst of new methodology for genome analysis around diseases coming from hundreds of groups around the world. Specific computational methods and strategies are being designed and improved around the identification and interpretation of genomic variation. The identification and classification of different types of genomic variants in the context of biomedicine is a key and foundational step for the development of a personalized medicine. This has been particularly central in the field of cancer genomics, which has based the research of the past ten to fifteen years in the sequencing of genomic DNA, and the identification and interpretation of (mostly) somatic and germline variation. Throughout these years, a large number of methods for variant detection have been developed with different action ranges. Despite all these developments, the identification of genomic variants has still room for improvement, not only at the level of sensitivity and specificity, but also at the computational level. Given the emergence of many initiatives for personalized medicine around the world, and the expected number of genomes that will have to be analyzed within health care systems, we require robust algorithms, designed together with a matching implementation that will minimize the computational costs of the analysis. With this aim, during this thesis, I have pushed and designed and implemented an algorithm for the efficient processing of genomic data, in close collaboration with computer scientists of our center that defined the implementation, focusing on lowering the energy and the time of the analysis. This methodology, which relies on a reference free approach of read classification, has been protected with a patent, and is being used as the foundation for the development of SMuFin2, a more accurate and computationally efficient version of the initial SMuFin from 2014. We here show that our method is able to process whole genome sequences very fast and with a minimal energy consumption, compared with existing methods, and that has great potential for the identification of all ranges of variants, including insertions of non-human DNA. Further developments on SMuFin2 are needed to finally assess its full variant calling capabilities. Despite their great importance and their clear role in the biology of the cell, somatic variation that occurs in healthy tissues has remained diffuse in their roles. In the case of development, some hypotheses have been proposed to explain the observed somatic DNA damage that occurs during brain development (e.g., replication stress). But the real impact and the underlying mechanisms of this somatic variation are not yet understood. In order to seed light on the type and potential functional impact of somatic variation in brain development, we established a new collaboration to identify, and describe somatic DNA rearrangements induced by Pgbd5 during brain development and adult state in 36 mice neural tissue samples. The detection of somatic variants in healthy tissues presents more challenges than in the cancer scenario, where a variant is present in a significant number of cells and is easier to detect. We have identified, classified and interpreted the landscape of somatic variation in neural development and identified interesting differences between adult and embryonic variation load, and specific types of variants, as the potential result of the activity of these transposase-like genes.Universitat de BarcelonaTorrents Arenales, DavidGelpí Buchaca, Josep LluísUniversitat de Barcelona. Facultat de Biologia202120212020info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion277 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/672163TDX (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:10803/6721632026-06-14T12:46:07Z
score 15,301603

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