The Data are Insufficient to Confidently Root the SARS-CoV-2 Phylogenetic Tree

2025/06/01 by Jesse D. Bloom · 1 voice
Mathematics · Medicine · #COVID-19 diagnosis using AI #COVID-19 epidemiological studies #SARS-CoV-2 and COVID-19 Research

paper · pdf · doi:10.1093/molbev/msaf118

openalex publication_date 2025/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Several years ago, I published a paper that described the discrepancy between outgroup and date-based methods for rooting the SARS-CoV-2 phylogenetic tree, and proposed the discrepancy could arise from biases among the available early viral sequences. Here, I explain why the root remains uncertain, including via an interactive narrative at https://nextstrain.org/groups/jbloomlab/narratives/SARS2-rooting/early-SARS2-trees-v1 that enables the reader to examine the underlying data and understand discrepancies that lead different methods to reach different inferences about the root. I also demonstrate clear evidence of bias among the earliest available sequences, and explain why the root of the SARS-CoV-2 tree cannot be conclusively resolved with the current data.

Citations

• Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
• Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
• Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia
• IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era
• A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology
• Sustainable data analysis with Snakemake
• Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market
• Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency
• A Critical Reexamination of Recovered SARS-CoV-2 Sequencing Data
• Proximity Ascertainment Bias in Early Covid Case Locations
• Surveillance of SARS-CoV-2 at the Huanan Seafood Market
• The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2
• The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic

Discussions

• @jbloomlab.bsky.social argues that the earliest available sequences of SARS-CoV-2 are not fully representative of actual early cases. 🔗 doi.org/10.1093/molbev/msaf118 #evobio #molbio #covid19 #sars [bsky, 2 points, 1 comments]

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