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Estimated genealogies are fundamental to understanding this ocean of data and form the primary input to many downstream analyses. A basic assumption of methods to infer genealogies from viral genetic data is that recombination is negligible and the genealogy is a tree. However, recombinant lineages have risen to global prevalence, and simple tree representations are therefore incomplete and potentially misleading. We present sc2ts, a method to infer reticulate genealogies as an Ancestral Recombination Graph (ARG) in real time at pandemic scale. We infer an ARG for 2.48 million SARS-CoV-2 genomes, which leverages the widely used tskit software ecosystem to support further analyses and visualisation. This rich and validated resource clarifies the relationships among recombinant lineages, quantifies the rate of recombination over time, and provides a lower bound on detectable recombination.<\/jats:p>","DOI":"10.1101\/2023.06.08.544212","type":"posted-content","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:00:20Z","timestamp":1686276020000},"source":"Crossref","is-referenced-by-count":16,"title":["A Pandemic-Scale Ancestral Recombination Graph for SARS-CoV-2"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6351-8873","authenticated-orcid":false,"given":"Shing H","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3536-6411","authenticated-orcid":false,"given":"Yan","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-9396","authenticated-orcid":false,"given":"Anastasia","family":"Ignatieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-7756","authenticated-orcid":false,"given":"Katherine","family":"Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-7226","authenticated-orcid":false,"given":"Isobel","family":"Guthrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-6801","authenticated-orcid":false,"given":"Benjamin","family":"Jeffery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-0047","authenticated-orcid":false,"given":"Duncan S","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1543-4501","authenticated-orcid":false,"given":"Carmen Lia","family":"Murall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-0818","authenticated-orcid":false,"given":"Sarah","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-5253","authenticated-orcid":false,"given":"Jerome","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023061309150511000_2023.06.08.544212v1.1","doi-asserted-by":"crossref","first-page":"e76854","DOI":"10.7554\/eLife.76854","article-title":"Reconstruction of transmission chains of SARS-CoV-2 amidst multiple outbreaks in a geriatric acute-care hospital: A combined retrospective epidemiological and genomic study","volume":"11","year":"2022","journal-title":"eLife"},{"issue":"67","key":"2023061309150511000_2023.06.08.544212v1.2","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.21105\/joss.03773","article-title":"Nextclade: Clade assignment, mutation calling and quality control for viral genomes","volume":"6","year":"2021","journal-title":"Journal of Open Source Software"},{"issue":"1","key":"2023061309150511000_2023.06.08.544212v1.3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3390\/v14010078","article-title":"The remarkable evolutionary plasticity of coronaviruses by mutation and recombination: insights for the covid-19 pandemic and the future evolutionary paths of sars-cov-2","volume":"14","year":"2022","journal-title":"Viruses"},{"key":"2023061309150511000_2023.06.08.544212v1.4","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511808999"},{"issue":"9","key":"2023061309150511000_2023.06.08.544212v1.5","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41576-022-00483-8","article-title":"Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic","volume":"23","year":"2022","journal-title":"Nature Reviews Genetics"},{"issue":"1","key":"2023061309150511000_2023.06.08.544212v1.6","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1038\/s41467-022-33910-9","article-title":"Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France","volume":"13","year":"2022","journal-title":"Nature Communications"},{"key":"2023061309150511000_2023.06.08.544212v1.7","doi-asserted-by":"crossref","unstructured":"Baumdicker, F. , Bisschop, G. , Goldstein, D. , Gower, G. , Ragsdale, A. 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