Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification
Frontiers in Immunology, vol. 12, pp. 637164
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% (CI 95% 82.2–100%). A three-transcript signature ( FCGR1A, ZNF296, and C1QB ) differentiated TB from LTBI (AUC 97.3%, CI 95% : 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.
Authors 21
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Affiliation as printed
National Public Health Speciality Training Programme, South West, United Kingdom
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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Myrsini Kaforou corresponding
Affiliation as printed
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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Hammersmith Hospital · Imperial College London
Affiliation as printed
Centre for Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom
Imperial Molecular Pathology, Imperial Healthcare Trust, Hammersmith Hospital, London, United Kingdom
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Affiliation as printed
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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The University of Queensland · Institute for Molecular Bioscience
Affiliation as printed
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
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Affiliation as printed
School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
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Brighton and Sussex Medical School · Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Affiliation as printed
Brighton and Malawi Liverpool Wellcome Trust Unit, Blantyre, Malawi
Brighton and Sussex Medical School, Brighton, United Kingdom
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National Health Service · University of Oxford · Oxford University Hospitals NHS Trust
Affiliation as printed
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
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London School of Hygiene & Tropical Medicine · Malawi Epidemiology and Intervention Research Unit
Affiliation as printed
Karonga Prevention Study, Chilumba, Malawi
London School of Hygiene & Tropical Medicine, London, United Kingdom
Malawi Epidemiology and Intervention Research Unit, Chilumba, Malawi
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University of Cape Town · Red Cross War Memorial Children's Hospital
Affiliation as printed
Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Cape Town, South Africa
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Affiliation as printed
Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom
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Brighton and Sussex Medical School · National Health Service · University of Sussex · Brighton and Sussex University Hospitals NHS Trust
Affiliation as printed
Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
Brighton and Sussex University Hospitals National Health Service (NHS) Trust, Brighton, United Kingdom
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Affiliation as printed
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
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London School of Hygiene & Tropical Medicine
Affiliation as printed
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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National Health Service · University of Liverpool · Royal Liverpool and Broadgreen University Hospital NHS Trust · Broadgreen Hospital
Affiliation as printed
Centre for Global Vaccine Research, Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom
Tropical and Infectious Disease Unit, Royal Liverpool and Broadgreen University Hospitals National Health Service (NHS) Trust, Liverpool, United Kingdom
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Affiliation as printed
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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London School of Hygiene & Tropical Medicine
Affiliation as printed
Department of Immunology and Infection, and Tuberculosis (TB) Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom
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The University of Queensland · Institute for Molecular Bioscience
Affiliation as printed
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
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University of Cape Town · The Francis Crick Institute · Wellcome Centre for Infectious Diseases Research in Africa · Institute of Infectious Disease and Molecular Medicine · Imperial College London
Affiliation as printed
Department of Medicine, Imperial College London, London, United Kingdom
The Francis Crick Institute, London, United Kingdom
Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
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Affiliation as printed
Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
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