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

Posted on 02.03.2021 - 04:03

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 diagnostic test development. To identify minimal transcript signatures, we applied a 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 further investigated using reverse transcriptase (RT)—digital PCR (dPCR). A four-transcript signature (GBP6, TMCC1, PRDM1, and 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, and 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.

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Gliddon, Harriet D.; Kaforou, Myrsini; Alikian, Mary; Habgood-Coote, Dominic; Zhou, Chenxi; Oni, Tolu; et al. (2021): Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification. Frontiers. Collection. https://doi.org/10.3389/fimmu.2021.637164
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AUTHORS (21)

Harriet D. Gliddon
Myrsini Kaforou
Mary Alikian
Dominic Habgood-Coote
Chenxi Zhou
Tolu Oni
Suzanne T. Anderson
Andrew J. Brent
Amelia C. Crampin
Brian Eley
Robert Heyderman
Florian Kern
Paul R. Langford
Tom H. M. Ottenhoff
Martin L. Hibberd
Neil French
Victoria J. Wright
Hazel M. Dockrell
Lachlan J. Coin
Robert J. Wilkinson
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