PT  - JOURNAL ARTICLE
AU  - Harriet D. Gliddon
AU  - Myrsini Kaforou
AU  - Mary Alikian
AU  - Dominic Habgood-Coote
AU  - Chenxi Zhou
AU  - Tolu Oni
AU  - Suzanne T. Anderson
AU  - Andrew J. Brent
AU  - Amelia C. Crampin
AU  - Brian Eley
AU  - Florian Kern
AU  - Paul R. Langford
AU  - Tom H. M. Ottenhoff
AU  - Martin L. Hibberd
AU  - Neil French
AU  - Victoria J. Wright
AU  - Hazel M. Dockrell
AU  - Lachlan J. Coin
AU  - Robert J. Wilkinson
AU  - Michael Levin
AU  - on behalf of the ILULU Consortium
TI  - Identification of reduced host transcriptomic signatures for tuberculosis and digital PCR-based validation and quantification
AID  - 10.1101/583674
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 583674
4099  - http://biorxiv.org/content/early/2019/03/21/583674.short
4100  - http://biorxiv.org/content/early/2019/03/21/583674.full
AB  - Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate the development of diagnostic tests.To identify minimal transcript signatures, we applied a novel transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were validated using reverse transcriptase (RT) - digital PCR (dPCR).A four-transcript signature (GBP6, TMCC1, PRDM1, ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2 – 100%). A three-transcript signature (FCGR1A, ZNF296, C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3 – 100%), regardless of HIV.These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.