OAPGC: a high-quality oral and airway prokaryotic genome catalog for enhanced ecological resolution and disease inference

The human oral cavity and airway harbor diverse microbiomes that are implicated in oral and respiratory diseases, yet comprehensive genomic catalogs remain scarce. Here, we present the Oral and Airway Prokaryotic Genome Catalog (OAPGC), comprising 99,215 high-quality, non-redundant genomes reconstructed from public and newly sequenced metagenomes and isolates. OAPGC was clustered into 2474 species using refined, phylum-specific nucleotide identity thresholds, and 29.5% of them are uncultured. Habitat-driven divergence was evident across 15 oral and 8 airway sites, with airway microbiomes showing greater inter-individual variability and enriched antibiotic resistance genes. Across 25 case–control comparisons covering 12 diseases, disease status explained significant community shifts in 19 datasets, with classifiers achieving an AUC > 0.70 in 20 datasets. Shared microbial signatures were identified for diseases such as periodontitis and pneumonia, including uncultured taxa. We also detected 12.3% of OAPGC species in the gut, whose enrichment was linked to multiple diseases and improved cross-cohort classification performance. OAPGC establishes a foundational, disease-relevant genomic framework for oral and airway microbiome studies.