tsdate-gel-paper

Publicly shareable code and plot data for the "Tracing the evolutionary histories of ultra-rare variants using variational dating of large ancestral recombination graphs" manuscript

Nathaniel S. Pope, Sam Tallman, Ben Jeffery, Duncan Robertson, Yan Wong, Savita Karthikeyan, Peter L. Ralph, and Jerome Kelleher (2026) Tracing the evolutionary histories of ultra-rare variants using variational dating of large ancestral recombination graphs. bioRxiv: 2026.01.07.698223; doi: https://doi.org/10.64898/2026.01.07.698223

• The gel_analysis directory contains all details on the analyses performed on Genomics England data. Please see the README in that directory for more details.
• The scripts directory contains scripts to run benchmarks and analysis on data sources that are not from Genomics England. Please see the README in that directory for more details.
• The tools and makefiles directory contain Makefiles used by files in scripts. Please see the README in scripts for more details.
• The tsinfer-snakemake directory contains a copy of the Snakemake workflow used to infer and date the ARGs. Please see the README in that directory for its source and licence.
• The data directory contains the data needed to make the plots, and figures is where the plots are written.

Archive

A snapshot of this repository, including the copy of the Snakemake workflow, is archived on Zenodo: https://doi.org/10.5281/zenodo.23142020

Data

• Allele ages for non-rare variants (DAC > 20) in the Genomics England data: https://doi.org/10.5281/zenodo.23038476
• Inferred ARGs for chromosomes 17 and 20 of the 1000 Genomes Project: https://doi.org/10.5281/zenodo.23086785

The full allele age dataset and inferred ARGs for Genomics England are available to approved researchers within the Genomics England Research Environment.

Software

The methods are implemented in tsdate and tsinfer, which are available from PyPI.

Licence

The code in this repository is released under the MIT licence (see LICENSE), except for tsinfer-snakemake, which is distributed under its own MIT licence.

The following data files come from published work. They are included with attribution and are not covered by the MIT licence:

• data/Phlash_fig7b.csv: PHLASH population size estimates from Terhorst (2025), Nature Genetics 57:2570–2577, https://doi.org/10.1038/s41588-025-02323-x; included with the author's permission.
• data/chr17inversion/chr17q21.31_time_plot.csv: Relate-based age estimates for the 17q21.31 inversion from Ignatieva et al. (2025), Molecular Biology and Evolution 42:msaf190, https://doi.org/10.1093/molbev/msaf190 (also available at https://github.com/a-ignatieva/dolores-paper).
• data/chr17inversion/donnelly_et_al_table_2.csv: 17q21 inversion marker SNPs from Table 2 of Donnelly et al. (2010), American Journal of Human Genetics 86:161–171.