Decomposition of the S. aureus pangenome reveals evolving genetic repertoire associated with adaptation and virulence.

Non-negative matrix factorization decomposes the accessory pangenome of 1,398 curated Staphylococcus aureus genomes into 24 additive gene modules, separating lineage phylons from mobilome phylons with 90% reconstruction accuracy.

• Why it matters: Existing pangenome methods either force genomes into single phylogenetic groups or analyze genes independently, leaving the composite mix of vertical lineage backgrounds and horizontal mobile elements unresolved.
• What they did: The authors applied non-negative matrix factorization to the accessory pangenome, validating module assignments with geNomad (75–96% of mobilome instances in prophage regions) and testing on 966 independent draft assemblies (mean AUC=0.996).
• The result: The additive phylon representation recovers known clonal complex and immune evasion patterns, links CC30 and hybrid ST239 via multiple horizontal transfers, and enables host and resistance discrimination plus rapid classification with phylon_assign.

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