Clustering of somatic mutations across cancer genomes

Sequencing of cancer genomes reveals the story of mutational events shaping the distribution of somatic mutations across the nucleotide sequence. A particular pattern of such distribution, mutational clustering, can inform about the genomic elements driving tumour development as well as localised mu...

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Detalhes bibliográficos
Autor: Arnedo Pac, Claudia Rosario
Tipo de documento: tese
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:CBUC, CESCA
Repositório:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/687381
Acesso em linha:http://hdl.handle.net/10803/687381
Access Level:Acceso aberto
Palavra-chave:Cancer genomics
Somatic mutations
Mutational processes
Mutational clustering
Mutational hotspots
Genòmica del càncer
Mutacions somàtiques
Processos mutacionals
Aglomeracions mutacionals
Hotspots mutacionals
575
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spelling Clustering of somatic mutations across cancer genomesArnedo Pac, Claudia RosarioCancer genomicsSomatic mutationsMutational processesMutational clusteringMutational hotspotsGenòmica del càncerMutacions somàtiquesProcessos mutacionalsAglomeracions mutacionalsHotspots mutacionals575Sequencing of cancer genomes reveals the story of mutational events shaping the distribution of somatic mutations across the nucleotide sequence. A particular pattern of such distribution, mutational clustering, can inform about the genomic elements driving tumour development as well as localised mutational processes acting under neutrality. Herein, we developed OncodriveCLUSTL, a new method to identify coding and non-coding cancer drivers on any species based on clustering signals, which shows a good performance individually and in combination with others. Secondly, we have systematically analysed the mutational processes underlying the formation of passenger hotspots across cancer genomes. We found mutational signatures 1 and 17 had the highest propensity to form hotspots among common mutational processes and identified different factors playing a role in it. Still, a large part of hotspot propensity remained unexplained, highlighting the need for identifying the complete set of mutational processes underlying hotspots formation to accurately measure neutral mutagenesis.Les seqüències dels genomes del càncer ens informen sobre els mecanismes responsables de la distribució de mutations somàtiques al llarg del genoma. Mitjançant les aglomeracions de mutacions somàtiques o “clustering”, podem detectar elements genòmics sota selecció positiva en càncer, anomenats “drivers”, així com processos mutacionals localitzats que actuen sota evolució neutral. En aquest treball hem desenvolupat OncodriveCLUSTL, un nou mètode basat clustering per identificar drivers codificants i no codificants al genoma humà i d’altres espècies, que mostra un bon rendiment individualment i en combinació amb altres. En segon lloc, hem dut a terme una anàlisi sistemàtica dels processos mutacionals que generen posicions amb mutacions recurrents o “hotspots”. Hem trobat que les firmes mutacionals 1 i 17 són les més propenses a formar hotspots i hem identificat diferents factors que hi juguen un paper. Tot i així, una gran part d’aquesta tendència encara no es pot explicar, fet que posa de manifest la necessitat d’identificar el conjunt complet de processos mutacionals responsables de la formació de hotspots per mesurar amb precisió la mutagènesi sota neutralitat.Programa de doctorat en BiomedicinaUniversitat Pompeu FabraLópez Bigas, NúriaGonzález Pérez, AbelUniversitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida202320232022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion245 p.application/pdfhttp://hdl.handle.net/10803/687381TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6873812026-06-14T12:46:07Z
dc.title.none.fl_str_mv Clustering of somatic mutations across cancer genomes
title Clustering of somatic mutations across cancer genomes
spellingShingle Clustering of somatic mutations across cancer genomes
Arnedo Pac, Claudia Rosario
Cancer genomics
Somatic mutations
Mutational processes
Mutational clustering
Mutational hotspots
Genòmica del càncer
Mutacions somàtiques
Processos mutacionals
Aglomeracions mutacionals
Hotspots mutacionals
575
title_short Clustering of somatic mutations across cancer genomes
title_full Clustering of somatic mutations across cancer genomes
title_fullStr Clustering of somatic mutations across cancer genomes
title_full_unstemmed Clustering of somatic mutations across cancer genomes
title_sort Clustering of somatic mutations across cancer genomes
dc.creator.none.fl_str_mv Arnedo Pac, Claudia Rosario
author Arnedo Pac, Claudia Rosario
author_facet Arnedo Pac, Claudia Rosario
author_role author
dc.contributor.none.fl_str_mv López Bigas, Núria
González Pérez, Abel
Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida
dc.subject.none.fl_str_mv Cancer genomics
Somatic mutations
Mutational processes
Mutational clustering
Mutational hotspots
Genòmica del càncer
Mutacions somàtiques
Processos mutacionals
Aglomeracions mutacionals
Hotspots mutacionals
575
topic Cancer genomics
Somatic mutations
Mutational processes
Mutational clustering
Mutational hotspots
Genòmica del càncer
Mutacions somàtiques
Processos mutacionals
Aglomeracions mutacionals
Hotspots mutacionals
575
description Sequencing of cancer genomes reveals the story of mutational events shaping the distribution of somatic mutations across the nucleotide sequence. A particular pattern of such distribution, mutational clustering, can inform about the genomic elements driving tumour development as well as localised mutational processes acting under neutrality. Herein, we developed OncodriveCLUSTL, a new method to identify coding and non-coding cancer drivers on any species based on clustering signals, which shows a good performance individually and in combination with others. Secondly, we have systematically analysed the mutational processes underlying the formation of passenger hotspots across cancer genomes. We found mutational signatures 1 and 17 had the highest propensity to form hotspots among common mutational processes and identified different factors playing a role in it. Still, a large part of hotspot propensity remained unexplained, highlighting the need for identifying the complete set of mutational processes underlying hotspots formation to accurately measure neutral mutagenesis.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
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/10803/687381
url http://hdl.handle.net/10803/687381
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 245 p.
application/pdf
dc.publisher.none.fl_str_mv Universitat Pompeu Fabra
publisher.none.fl_str_mv Universitat Pompeu Fabra
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
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score 15,301603

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