Novel interactive methods for ancient and mitochondrial DNA analysis

Abstract

The advent of next-generation sequencing technologies has led to a boom in DNA sequencing projects. Such high-throughput sequencing methods generate vast amounts of data that need to be comparatively analyzed to identify differences between different organisms or environmental conditions. In addition, it became possible to sequence the entire genomic content of a sample rather than just a single species. Such new technologies also enabled the analysis of ancient samples. These tasks require efficient computational methods that integrate genomic data from multiple sources in an automated, efficient, and reproducible manner. In this dissertation, contributions were made to analyzing metagenomic data sets and specific genomes of modern and ancient data sets.Since ancient DNA is usually highly damaged, new or adapted software is needed to meet the new challenges that arise. First, the software DamageProfiler is presented, efficiently calculating damage patterns typical for ancient DNA, such as base misincorporation frequency and fragment length. These features are used to verify the ancient origin of mapped DNA fragments and should be included in any analysis pipeline for ancient genome reconstruction. In addition, a GUI is also provided to make the software more accessible to inexperienced users. The second software presented is mitoBench, which focuses on analyzing complete modern and ancient human mitochondrial genomes. The workbench provides an interactive way to explore and visualize complete mitogenomes, focusing on applications with population genetics. The well-curated database linked to the workbench provides a mitochondrial DNA reference data set consisting of high-quality genomes and meta information. The final part of this thesis deals with the analysis of metagenomic data sets from ancient samples. Two applications of metagenomic analysis of previously under-studied tissues are described: the tissue of mummified Egyptian individuals and a human leg sample from an infant preserved in ethanol and paraffin. In addition to identifying the microbial composition of the samples, the applications show the successful recovery of DNA from various pathogens and subsequent genome reconstruction. Reconstruction of the ancient Mycobacterium leprae, hepatitis B virus, and Variola virus genomes has provided meaningful contributions to their geographical spread and insights into their evolution