Influenza A virus H5Nx genotypes assigned by genetic similarity are incongruent with global phylogenies

Genetic similarity–based H5Nx genotyping by GenoFlu and Genin2 is largely incongruent with global maximum-likelihood phylogenies, with only 14.2% of GenoFlu clusters monophyletic.

• Why it matters: Accurate H5Nx classification is needed to track variant emergence and spread, but reassortment and differing evolutionary histories can make similarity-based genotypes misleading.
• What they did: Using 41,366 publicly available H5Nx samples (2022–2025), genomes were assigned by GenoFlu (North America–focused) and Genin2 (Europe–focused), then compared against segment-by-segment phylogenies using TreeCluster and CD-HIT across multiple thresholds.
• The result: GenoFlu failed to assign many non–North/South America and Antarctica genomes, Genin2 struggled outside Europe/Africa/Western Asia, and several genotypes showed wide phylogenetic spans consistent with combining multiple reassortants.