A new blood-based RNA signature (R9), for monitoring effectiveness of tuberculosis treatment in a South Indian longitudinal cohort

Abstract

SummaryTuberculosis (TB) treatment involves a multidrug regimen for six months, and until two months, it is unclear if treatment is effective. This delay can lead to the evolution of drug resistance, lung damage, disease spread, and transmission. We identify a blood-based 9-gene signature using a computational pipeline that constructs and interrogates a genome-wide transcriptome-integrated protein-interaction network. The identified signature is able to determine treatment response at week 1–2 in three independent public datasets. Signature-based R9-score correctly detected treatment response at individual timepoints (204 samples) from a newly developed South Indian longitudinal cohort involving 32 patients with pulmonary TB. These results are consistent with conventional clinical metrics and can discriminate good from poor treatment responders at week 2 (AUC 0.93(0.81–1.00)). In this work, we provide proof of concept that the R9-score can determine treatment effectiveness, making a case for designing a larger clinical study.