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

Gliddon, HD, Kaforou, M, Alikian, M, Habgood-Coote, D, Zhou, C, Oni, T, Anderson, ST, Brent, AJ, Crampin, AC, Eley, B, Heyderman, R, Kern, F, Langford, PR, Ottenhoff, THM, Hibberd, ML, French, N, Wright, VJ, Dockrell, HM, Coin, LJ, Wilkinson, RJ and Levin, M. 2021. Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification. [Online]. Frontiers in Immunology. Available from: https://doi.org/10.3389/fimmu.2021.637164.s001

Gliddon, HD, Kaforou, M, Alikian, M, Habgood-Coote, D, Zhou, C, Oni, T, Anderson, ST, Brent, AJ, Crampin, AC, Eley, B, Heyderman, R, Kern, F, Langford, PR, Ottenhoff, THM, Hibberd, ML, French, N, Wright, VJ, Dockrell, HM, Coin, LJ, Wilkinson, RJ and Levin, M. Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification [Internet]. Frontiers in Immunology; 2021. Available from: https://doi.org/10.3389/fimmu.2021.637164.s001

Gliddon, HD, Kaforou, M, Alikian, M, Habgood-Coote, D, Zhou, C, Oni, T, Anderson, ST, Brent, AJ, Crampin, AC, Eley, B, Heyderman, R, Kern, F, Langford, PR, Ottenhoff, THM, Hibberd, ML, French, N, Wright, VJ, Dockrell, HM, Coin, LJ, Wilkinson, RJ and Levin, M (2021). Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification. [Data Collection]. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.637164.s001

Description

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.

Methods

Data capture method	Experiment
Date (Date published in a 3rd party system)	2 March 2021
Language(s) of written materials	English

People & Groups

Data Creators	Gliddon, HD, Kaforou, M, Alikian, M, Habgood-Coote, D, Zhou, C, Oni, T, Anderson, ST, Brent, AJ, Crampin, AC, Eley, B, Heyderman, R, Kern, F, Langford, PR, Ottenhoff, THM, Hibberd, ML, French, N, Wright, VJ, Dockrell, HM, Coin, LJ, Wilkinson, RJ and Levin, M
LSHTM Faculty/Department	Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Participating Institutions	London School of Hygiene & Tropical Medicine, London, United Kingdom