<p>Nature Methods, Published online: 09 February 2026; <a href="https://www.nature.com/articles/s41592-025-02932-8">doi:10.1038/s41592-025-02932-8</a></p>Performing pandemic-scale phylogenetic analysis poses multifaceted challenges. This study develops methods for identifying and accounting for mutation rate variation and recurrent sequence errors, leading to an improved global phylogenetic tree of >2 million severe acute respiratory syndrome coronavirus 2 genomes.