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A Pandemic-Scale Ancestral Recombination Graph for SARS-CoV-2
Shing H Zhan1,2,3, Yan Wong1,4, Anastasia Ignatieva5,4
1Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, United Kingdom.
Biorxiv : the Preprint Server for Biology
|November 26, 2025
Summary
This study introduces sc2ts, a new method to analyze SARS-CoV-2 genome data by inferring complex genealogies called Ancestral Recombination Graphs (ARGs). This approach accurately captures the impact of recombination in viral evolution.
Area of Science:
- Genomics
- Epidemiology
- Computational Biology
Background:
- The COVID-19 pandemic generated millions of SARS-CoV-2 genome sequences, creating a rich dataset for evolutionary analysis.
- Traditional phylogenetic methods assume negligible recombination, representing viral genealogies as simple trees, which is insufficient given the prevalence of recombinant lineages.
Purpose of the Study:
- To develop and apply a scalable method for inferring reticulate (non-tree-like) genealogies from large viral genomic datasets.
- To accurately represent the evolutionary history of SARS-CoV-2, accounting for recombination events.
Main Methods:
- Development of sc2ts, a novel method for real-time inference of Ancestral Recombination Graphs (ARGs) at pandemic scale.
- Application of sc2ts to infer an ARG for 2.48 million SARS-CoV-2 genomes.
- Leveraging the tskit software ecosystem for efficient data handling, analysis, and visualization.
Main Results:
- Inference of a large-scale ARG for 2.48 million SARS-CoV-2 genomes, providing a detailed view of viral evolution.
- Clarification of relationships among recombinant SARS-CoV-2 lineages.
- Quantification of the rate of recombination over time and establishment of a lower bound for detectable recombination.
Conclusions:
- The sc2ts method provides a powerful tool for understanding viral evolution in the presence of recombination.
- The inferred ARG offers a validated resource for further downstream analyses and visualizations of SARS-CoV-2 evolution.
- This work highlights the importance of considering recombination in phylogenetic studies of rapidly evolving viruses like SARS-CoV-2.
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