Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783667809372340224
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
work_keys_str_mv AT gliddonharrietd identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT kaforoumyrsini identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT alikianmary identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT habgoodcootedominic identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT zhouchenxi identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT onitolu identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT andersonsuzannet identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT brentandrewj identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT crampinameliac identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT eleybrian identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT heydermanrobert identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT kernflorian identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT langfordpaulr identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT ottenhofftomhm identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT hibberdmartinl identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT frenchneil identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT wrightvictoriaj identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT dockrellhazelm identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT coinlachlanj identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT wilkinsonrobertj identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification
AT levinmichael identificationofreducedhosttranscriptomicsignaturesfortuberculosisdiseaseanddigitalpcrbasedvalidationandquantification