Authors:	Sell, Christian
Title:	Addressing challenges of ancient DNA sequence data obtained with next generation methods
Online publication date:	3-May-2017
Year of first publication:	2017
Language:	english
Abstract:	This thesis addresses challenges in the bioinformatic analysis of palaeogenomes that were generated by Next Generation Sequencing of highly degrade ancient DNA from archaeological skeletal remains. It establishes a pipeline that incorporates a correction for postmortem damage as well as sequencing errors, to facilitate the comparison with sequence data from modern specimen. By applying the pipeline to published ancient genomes from the Aegean Neolithic and by comparing the results to data from the 1000 Genomes project, it could be shown that an excess of Cytosine to Thymine transitions linked to deaminations during the postmortem degradation of the DNA, can be reverted by bioinformatic processing. In another attempt to address the complexity and scarcity of DNA from prehistorical specimen, an in-solution hybridization enrichment was designed. This method can counteract the relatively low endogenous DNA content in samples from prehistoric human skeletal remains by selectively enriching specifically designed regions. The developed capture array was analyzed in 21 skeletal human remains from a Bronze Age battlefield, resulting in an average read depth of 1.71x over the whole genome. The statistical analysis of data produced by this approach enables genomic inferences similar to those based on full genomes. Third the thesis addresses the false assignments of individual bar-code-indices to sequence samples. In a data set comprising 38 capture enriched mitochondrial genomes from prehistoric human remains, it could be shown that this sequencing error can mimic a cross contamination event during lab work. By identifying and removing affected reads, false positive variants could be reduced from ~38% to 0%.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-3885
URN:	urn:nbn:de:hebis:77-diss-1000012793
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	https://rightsstatements.org/vocab/InC/1.0/
Extent:	iii, 109 Seiten
Appears in collections:	JGU-Publikationen