Cross-Cohort Transcriptomic Prioritization and Chemical-Provenance Assessment of Asthma Airway-Brushing Genes...

Direct human evidence linking Scrophularia ningpoensis to asthma is limited, and database-derived herb-target records do not establish constituent exposure or target engagement. We used an evidence-audited molecular-informatics workflow to prioritize asthma airway-brushing-associated genes overlapping a frozen HERB export. GSE63142 was the discovery set, GSE67472 the independent airway-epithelial replication set, GSE137268 an induced-sputum cross-biospecimen transfer set, and GSE43696 a descriptive same-cohort reference because 105 of 108 identifiers overlapped GSE63142. Of 1266 measurable HERB-annotated targets, an 81-gene FDR-defined overlap did not exceed an expression-matched null (p = 0.0972), whereas a 19-gene strict overlap showed 2.27-fold enrichment (empirical p = 3.00 × 10^-4) and 12 genes met the prespecified replication criterion in GSE67472. Provenance sensitivity retained two genes after database-mining-only edges were excluded and none under a direct-target-engagement requirement. Nested classifiers transferred to GSE67472, but not to sputum. Out-of-fold SHAP identified model-specific contributors, with moderate cross-cohort rank stability for LASSO (Spearman ρ = 0.563) and random forest (ρ = 0.693); SHAP was not interpreted as causal or herbal-target importance. These findings support computational prioritization and transferability assessment, not chemical presence, exposure, target binding, mechanism, or efficacy.