Frontiers in Immunology (Mar 2021)
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification
- Harriet D. Gliddon,
- Harriet D. Gliddon,
- Myrsini Kaforou,
- Mary Alikian,
- Mary Alikian,
- Dominic Habgood-Coote,
- Chenxi Zhou,
- Tolu Oni,
- Suzanne T. Anderson,
- Suzanne T. Anderson,
- Andrew J. Brent,
- Andrew J. Brent,
- Amelia C. Crampin,
- Amelia C. Crampin,
- Amelia C. Crampin,
- Brian Eley,
- Brian Eley,
- Robert Heyderman,
- Florian Kern,
- Florian Kern,
- Paul R. Langford,
- Tom H. M. Ottenhoff,
- Martin L. Hibberd,
- Neil French,
- Neil French,
- Victoria J. Wright,
- Hazel M. Dockrell,
- Lachlan J. Coin,
- Robert J. Wilkinson,
- Robert J. Wilkinson,
- Robert J. Wilkinson,
- Michael Levin
Affiliations
- Harriet D. Gliddon
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- Harriet D. Gliddon
- National Public Health Speciality Training Programme, South West, United Kingdom
- Myrsini Kaforou
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- Mary Alikian
- Imperial Molecular Pathology, Imperial Healthcare Trust, Hammersmith Hospital, London, United Kingdom
- Mary Alikian
- Centre for Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom
- Dominic Habgood-Coote
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- Chenxi Zhou
- Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
- Tolu Oni
- School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- Suzanne T. Anderson
- Brighton and Sussex Medical School, Brighton, United Kingdom
- Suzanne T. Anderson
- Brighton and Malawi Liverpool Wellcome Trust Unit, Blantyre, Malawi
- Andrew J. Brent
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Andrew J. Brent
- 0Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
- Amelia C. Crampin
- 1Malawi Epidemiology and Intervention Research Unit, Chilumba, Malawi
- Amelia C. Crampin
- 2London School of Hygiene & Tropical Medicine, London, United Kingdom
- Amelia C. Crampin
- 3Karonga Prevention Study, Chilumba, Malawi
- Brian Eley
- 4Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
- Brian Eley
- 5Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
- Robert Heyderman
- 6Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom
- Florian Kern
- 7Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
- Florian Kern
- 8Brighton and Sussex University Hospitals National Health Service (NHS) Trust, Brighton, United Kingdom
- Paul R. Langford
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- Tom H. M. Ottenhoff
- 9Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
- Martin L. Hibberd
- 0Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Neil French
- 1Tropical and Infectious Disease Unit, Royal Liverpool and Broadgreen University Hospitals National Health Service (NHS) Trust, Liverpool, United Kingdom
- Neil French
- 2Centre for Global Vaccine Research, Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom
- Victoria J. Wright
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- Hazel M. Dockrell
- 3Department of Immunology and Infection, and Tuberculosis (TB) Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Lachlan J. Coin
- Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
- Robert J. Wilkinson
- 4The Francis Crick Institute, London, United Kingdom
- Robert J. Wilkinson
- 5Department of Medicine, Imperial College London, London, United Kingdom
- Robert J. Wilkinson
- 6Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
- Michael Levin
- Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
- DOI
- https://doi.org/10.3389/fimmu.2021.637164
- Journal volume & issue
-
Vol. 12
Abstract
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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