- Titel
- Haplotype-based Methods for aDNA Data Analysis
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-956593
- Datum der Einreichung
- 10.10.2024
- Datum der Verteidigung
- 07.02.2025
- Abstract (EN)
- This thesis focuses on new haplotype-based methods for analyzing ancient DNA (aDNA) data. Methods based on allele frequency have so far dominated the aDNA world and have been the primary workhorse that drives most of the exciting discoveries from aDNA in the past decade. However, it suffers from two shortcomings: first, it has low resolution for decoding the demography of the recent past because the widely used in-solution capture enrichment panel (1240k panel) mostly consists of common variants, which is not particularly informative about recent population history; second, it can produce biased results due to deep population structure. Haplotype-based methods (e. g., imputation, phasing) and their downstream tasks (e. g., identity-by-descent segments calling) have long been applied to DNA data collected from modern populations and have greatly advanced many areas of human genetics, including both medical and population genetics. However, progress has been lagging in the aDNA world. This thesis presents three new haplotype-based methods that open new avenues for aDNA data analysis. Chapter 2 introduces hapCon, a new method for estimating contamination rate in aDNA sequencing data that implicitly performs imputation on the haploid male X chromosome. Because hapCon’s ability to use linkage disequilibrium (LD) to draw information from neighboring sites and to use the Li&Stephen’s haplotype copying model to draw information from a large reference panel, it consistently outperforms previously published methods by producing estimates with much lower variance. Section 2.4 also introduces how hapCon can be extended to estimate contamination rate from runs of homozygosity (ROH), which allows it to be applied to female samples that contain 50cM or more ROH blocks as well. Chapter 3 introduces ancIBD, a new method for detecting identity-bydescent (IBD) segments from aDNA data with 0.25x coverage (WGS data) or 1x coverage (1240k data). The model was designed by Harald Ringbauer, my PhD supervisor, during his postdoc. I was mainly responsible for simulations and extending it to detecting IBD2 segments and to IBD detection on X chromosomes. Chapter 4 presents TTNe, a new method to estimate effective population size (Ne) trajectory from time-series IBD segments. This is particularly handy for the aDNA community because samples collected from the same site often date to different time periods. However, as most models are designed to work with modern DNA, they assume all samples are contemporaneous. Using simulations, we show that utilizing IBD sharing in time series has increased resolution to infer recent fluctuations in effective population sizes compared to methods that only use contemporaneous samples. Finally, we developed an approach for estimating and modeling IBD detection errors in empirical IBD analysis. To showcase the practical utility of TTNe, we applied it to two time transects of ancient genomes, individuals associated with the Copper Age Corded Ware Culture (CWC) and Medieval England. In both cases, we found evidence of a growing population, a signal consistent with archaeological records. Chapter 5 discusses possible directions for improving the works presented in this thesis.
- Verweis
- this is a paper that I co-authored with others. Part of the thesis is based on this paper.
Link: https://www.pnas.org/doi/10.1073/pnas.2401106122
Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments
DOI: https://doi.org/10.1073/pnas.2401106122 - Evidence for dynastic succession among early Celtic elites in Central Europe
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
Link: https://www.nature.com/articles/s41562-024-01888-7
DOI: 10.1038/s41562-024-01888-7 - Genetic estimates of the initial peopling of Polynesian islands actually reflect later inter-island contacts
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
Link: https://www.biorxiv.org/content/10.1101/2022.12.01.518673v1 - Estimating effective population size trajectories from time-series identity-by-descent segments
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
DOI: 10.1093/genetics/iyae212
Link: https://academic.oup.com/genetics/advance-article/doi/10.1093/genetics/iyae212/7978934 - hapCon: estimating contamination of ancient genomes by copying from reference haplotypes
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
DOI: 10.1093/bioinformatics/btac390
Link: https://www.pnas.org/doi/10.1073/pnas.2401106122 - Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
DOI: 10.1038/s41586-023-05726-0
Link: https://www.nature.com/articles/s41586-023-05726-0 - Accurate detection of identity-by-descent segments in human ancient DNA
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
DOI: 10.1038/s41588-023-01582-w
Link: https://www.nature.com/articles/s41588-023-01582-w - Earliest modern human genomes constrain timing of Neanderthal admixture
this is a paper that I co-authored with others. Part of the thesis is based on this paper.
DOI: 10.1038/s41586-024-08420-x
Link: https://www.nature.com/articles/s41586-024-08420-x - Freie Schlagwörter (EN)
- ancient DNA, identity-by-descent, population genetics, statistical genetics, bioinformatics
- Klassifikation (DDC)
- 500
- Den akademischen Grad verleihende / prüfende Institution
- Universität Leipzig, Leipzig
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-956593
- Veröffentlichungsdatum Qucosa
- 13.02.2025
- Dokumenttyp
- Dissertation
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0