Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification

Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification the concentrations signature transcripts in not reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training sets. Signatures were further investigated using reverse transcriptase (RT)—digital PCR (dPCR). A four-transcript ( GBP6, TMCC1, PRDM1 , ARG1 ) measured RT-dPCR distinguished those OD (area under curve (AUC) 93.8% (CI 95% 82.2–100%). three-transcript FCGR1A, ZNF296, C1QB differentiated LTBI (AUC 97.3%, CI : 93.3–100%), regardless HIV. These validated across platforms samples offering strong, quantitative support their use as biomarkers TB.