Computational Methods for the Analysis of Chromosomal Rearrangements

This dissertation focuses on algorithms for genome assembly and the interpretation of changes in genome architecture caused by structural rearrangements. The introductory chapter presents the biological background of the problem from a genetic perspective and discusses the state-of-the art sequencing technologies. The following chapter introduces an innovative algorithm designed for third-generation sequencing data. This method allows for the local assembly of regions enriched in segmental duplications. It has been utilized to reconstruct the subtelomeric sequences of selected chromosomes in Great Apes, leading to the formulation of important hypotheses about the impact of the ancestral chromosome fusion event on the evolution of pre-humans. Next, an enhanced method for determining the temporal extent of large chromosomal rearrangements is presented. This method has demonstrated its applicability in estimating the speciation times of species. The subsequent chapter introduces a method for enumerating all possible scenarios of complex chromosomal rearrangements. These rearrangements are modeled using Karyotype Graphs, which are constructed based on known breakpoints induced by the considered rearrangements. The chapter describes an algorithm for enumerating Minimal Linear Eulerian Decomposition of Karyotype Graphs, which works with a polynomial time delay complexity. Lastly, a web server enabling the clinical interpretation of structural variants is introduced. The web server features an innovative genome browser visualizing genomic regions from the rearrangement’s breakpoint perspective.