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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982854/ https://www.ncbi.nlm.nih.gov/pubmed/33763081 http://dx.doi.org/10.3389/fimmu.2021.637164 |
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author | Gliddon, Harriet D. Kaforou, Myrsini Alikian, Mary Habgood-Coote, Dominic Zhou, Chenxi Oni, Tolu Anderson, Suzanne T. Brent, Andrew J. Crampin, Amelia C. Eley, Brian Heyderman, Robert Kern, Florian Langford, Paul R. Ottenhoff, Tom H. M. Hibberd, Martin L. French, Neil Wright, Victoria J. Dockrell, Hazel M. Coin, Lachlan J. Wilkinson, Robert J. Levin, Michael |
author_facet | Gliddon, Harriet D. Kaforou, Myrsini Alikian, Mary Habgood-Coote, Dominic Zhou, Chenxi Oni, Tolu Anderson, Suzanne T. Brent, Andrew J. Crampin, Amelia C. Eley, Brian Heyderman, Robert Kern, Florian Langford, Paul R. Ottenhoff, Tom H. M. Hibberd, Martin L. French, Neil Wright, Victoria J. Dockrell, Hazel M. Coin, Lachlan J. Wilkinson, Robert J. Levin, Michael |
author_sort | Gliddon, Harriet D. |
collection | PubMed |
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% (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. |
format | Online Article Text |
id | pubmed-7982854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79828542021-03-23 Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification Gliddon, Harriet D. Kaforou, Myrsini Alikian, Mary Habgood-Coote, Dominic Zhou, Chenxi Oni, Tolu Anderson, Suzanne T. Brent, Andrew J. Crampin, Amelia C. Eley, Brian Heyderman, Robert Kern, Florian Langford, Paul R. Ottenhoff, Tom H. M. Hibberd, Martin L. French, Neil Wright, Victoria J. Dockrell, Hazel M. Coin, Lachlan J. Wilkinson, Robert J. Levin, Michael Front Immunol Immunology 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. Frontiers Media S.A. 2021-03-02 /pmc/articles/PMC7982854/ /pubmed/33763081 http://dx.doi.org/10.3389/fimmu.2021.637164 Text en Copyright © 2021 Gliddon, Kaforou, Alikian, Habgood-Coote, Zhou, Oni, Anderson, Brent, Crampin, Eley, Heyderman, Kern, Langford, Ottenhoff, Hibberd, French, Wright, Dockrell, Coin, Wilkinson and Levin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gliddon, Harriet D. Kaforou, Myrsini Alikian, Mary Habgood-Coote, Dominic Zhou, Chenxi Oni, Tolu Anderson, Suzanne T. Brent, Andrew J. Crampin, Amelia C. Eley, Brian Heyderman, Robert Kern, Florian Langford, Paul R. Ottenhoff, Tom H. M. Hibberd, Martin L. French, Neil Wright, Victoria J. Dockrell, Hazel M. Coin, Lachlan J. Wilkinson, Robert J. Levin, Michael Identification of Reduced Host Transcriptomic Signatures for Tuberculosis Disease and Digital PCR-Based Validation and Quantification |
title | 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_short | 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 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982854/ https://www.ncbi.nlm.nih.gov/pubmed/33763081 http://dx.doi.org/10.3389/fimmu.2021.637164 |
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