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Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness

2022; American Association for the Advancement of Science; Volume: 376; Issue: 6599 Linguagem: Inglês

10.1126/science.abm1208

1095-9203

Fritz Obermeyer, Martin Jankowiak, Nikolaos Barkas, S. F. Schaffner, Jesse D. Pyle, Leonid Yurkovetskiy, Matteo Bosso, Daniel J. Park, Mehrtash Babadi, Bronwyn MacInnis, Jeremy Luban, Pardis C. Sabeti, Jacob E. Lemieux,

vaccines and immunoinformatics approaches

Repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased fitness underscores the value of rapid detection and characterization of new lineages. We have developed PyR 0 , a hierarchical Bayesian multinomial logistic regression model that infers relative prevalence of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to fitness. Applying PyR 0 to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase fitness, including previously identified spike mutations and many nonspike mutations within the nucleocapsid and nonstructural proteins. PyR 0 forecasts growth of new lineages from their mutational profile, ranks the fitness of lineages as new sequences become available, and prioritizes mutations of biological and public health concern for functional characterization.