COMPUTATIONAL APPROACHES TO STUDYING THE CAUSES AND CONSEQUENCES OF MUTATIONAL SIGNATURES

Abstract

Deciphering mutational signatures provides insight into the causes and consequences of somatic mutagenesis in normal tissues and tumours. Mutational signature analysis has shown potential in clinical applications and revealed mechanisms underlying mutagenesis, including DNA repair, DNA replication infidelity, and the effects of endogenous and exogenous genotoxins. This thesis addresses in depth two aspects of the study of mutational signatures: (1) discovery of mutational signatures by data mining using an analytical approach based on the hierarchical Dirichlet process, and (2) the preferential impact of mutational signatures on transcription factor binding in particular biological pathways.