Transcriptomic Profiles of Confirmed Pediatric Tuberculosis Patients and Household Contacts Identifies Active Tuberculosis, Infection, and Treatment Response among Indian Children

Background: Gene expression profiling is emerging as a tool for tuberculosisdiagnosis and treatment response monitoring, but limited data specific to Indianchildren and incident tuberculosis infection (TBI) exist.Methods: 16 pediatric Indian tuberculosis cases were age- and sex-matched to 32tuberculosis-exposed controls (13 developed incident TBI without subsequent activetuberculosis). Longitudinal samples were collected for RNAseq. Differential expressionanalysis generated gene lists that identify tuberculosis diagnosis and tuberculosistreatment response. Data were compared with published gene lists. Population specificrisk score thresholds were calculated.Results: 71 genes identified tuberculosis diagnosis and 25 treatment response. Within group expression was partially explained by age, sex, and incident TBI. Transientchanges in gene expression were identified after both infection and treatment.Application of 27 published gene lists to our data found variable performance fortuberculosis diagnosis (sensitivity 0.38–1.00, specificity 0.48–0.93) and treatmentresponse (sensitivity 0.70–0.80, specificity 0.40–0.80). Our gene lists found similarlyvariable performance when applied to published datasets for diagnosis (sensitivity0.56–0.85, specificity 0.50–0.85) and treatment response (sensitivity 0.49– 0.86,specificity 0.50–0.84).Conclusions: Gene expression profiles among Indian children with confirmedtuberculosis were distinct from adult-derived gene lists, highlighting the importance ofincluding distinct populations in differential gene expression models.