Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification
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 sign...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.637164/full |
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doaj-179a6b2ee6174b478eec06f81b9547eb |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification Frontiers in Immunology tuberculosis transcriptomics dPCR gene expression signatures biomarkers |
| author_facet |
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 |
| author_sort |
Harriet D. Gliddon |
| title |
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
| title_short |
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
| title_full |
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
| title_fullStr |
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
| title_full_unstemmed |
Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
| title_sort |
identification of reduced host transcriptomic signatures for tuberculosis disease and digital pcr-based validation and quantification |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-03-01 |
| 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. |
| topic |
tuberculosis transcriptomics dPCR gene expression signatures biomarkers |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.637164/full |
| work_keys_str_mv |
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doaj-179a6b2ee6174b478eec06f81b9547eb2021-03-02T04:17:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.637164637164Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and QuantificationHarriet D. Gliddon0Harriet D. Gliddon1Myrsini Kaforou2Mary Alikian3Mary Alikian4Dominic Habgood-Coote5Chenxi Zhou6Tolu Oni7Suzanne T. Anderson8Suzanne T. Anderson9Andrew J. Brent10Andrew J. Brent11Amelia C. Crampin12Amelia C. Crampin13Amelia C. Crampin14Brian Eley15Brian Eley16Robert Heyderman17Florian Kern18Florian Kern19Paul R. Langford20Tom H. M. Ottenhoff21Martin L. Hibberd22Neil French23Neil French24Victoria J. Wright25Hazel M. Dockrell26Lachlan J. Coin27Robert J. Wilkinson28Robert J. Wilkinson29Robert J. Wilkinson30Michael Levin31Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomNational Public Health Speciality Training Programme, South West, United KingdomSection of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomImperial Molecular Pathology, Imperial Healthcare Trust, Hammersmith Hospital, London, United KingdomCentre for Haematology, Faculty of Medicine, Imperial College London, London, United KingdomSection of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, AustraliaSchool of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaBrighton and Sussex Medical School, Brighton, United KingdomBrighton and Malawi Liverpool Wellcome Trust Unit, Blantyre, MalawiNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom0Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom1Malawi Epidemiology and Intervention Research Unit, Chilumba, Malawi2London School of Hygiene & Tropical Medicine, London, United Kingdom3Karonga Prevention Study, Chilumba, Malawi4Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Cape Town, South Africa5Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa6Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom7Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom8Brighton and Sussex University Hospitals National Health Service (NHS) Trust, Brighton, United KingdomSection of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom9Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands0Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom1Tropical and Infectious Disease Unit, Royal Liverpool and Broadgreen University Hospitals National Health Service (NHS) Trust, Liverpool, United Kingdom2Centre for Global Vaccine Research, Institute of Infection & Global Health, University of Liverpool, Liverpool, United KingdomSection of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom3Department of Immunology and Infection, and Tuberculosis (TB) Centre, London School of Hygiene and Tropical Medicine, London, United KingdomInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia4The Francis Crick Institute, London, United Kingdom5Department of Medicine, Imperial College London, London, United Kingdom6Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaSection of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United KingdomRecently, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.637164/fulltuberculosistranscriptomicsdPCRgene expressionsignaturesbiomarkers |