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...
| Autor: | |
|---|---|
| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/687381 |
| Acceso en línea: | http://hdl.handle.net/10803/687381 |
| Access Level: | acceso abierto |
| Palabra clave: | Cancer genomics Somatic mutations Mutational processes Mutational clustering Mutational hotspots Genòmica del càncer Mutacions somàtiques Processos mutacionals Aglomeracions mutacionals Hotspots mutacionals 575 |
| Sumario: | 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. |
|---|