Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children

Abstract Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood...

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Autores principales:	John Espen Gjøen, Synne Jenum, Dhanasekaran Sivakumaran, Aparna Mukherjee, Ragini Macaden, Sushil K. Kabra, Rakesh Lodha, Tom H. M. Ottenhoff, Marielle C. Haks, Timothy Mark Doherty, Christian Ritz, Harleen M. S. Grewal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e3c7dd1d08254a8dbb04f27f1e98da63
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spelling	oai:doaj.org-article:e3c7dd1d08254a8dbb04f27f1e98da632021-12-02T11:52:59ZNovel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children10.1038/s41598-017-05057-x2045-2322https://doaj.org/article/e3c7dd1d08254a8dbb04f27f1e98da632017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05057-xhttps://doaj.org/toc/2045-2322Abstract Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood of Indian children, capable of discriminating intra-thoracic TB disease from other symptomatic illnesses. We investigated the expression of 198 genes in a training set, comprising 47 TB cases (19 definite/28 probable) and 36 asymptomatic household controls, and identified a 7- and a 10-transcript signature, both including NOD2, GBP5, IFITM1/3, KIF1B and TNIP1. The discriminatory abilities of the signatures were evaluated in a test set comprising 24 TB cases (17 definite/7 probable) and 26 symptomatic non-TB cases. In separating TB-cases from symptomatic non-TB cases, both signatures provided an AUC of 0.94 (95%CI, 0.88–1.00), a sensitivity of 91.7% (95%CI, 71.5–98.5) regardless of culture status, and 100% sensitivity for definite TB. The 7-transcript signature provided a specificity of 80.8% (95%CI, 60.0–92.7), and the 10-transcript signature a specificity of 88.5% (95%CI, 68.7–96.9%). Although warranting exploration and validation in other populations, our findings are promising and potentially relevant for future non-sputum based POC diagnostic tools for pediatric TB.John Espen GjøenSynne JenumDhanasekaran SivakumaranAparna MukherjeeRagini MacadenSushil K. KabraRakesh LodhaTom H. M. OttenhoffMarielle C. HaksTimothy Mark DohertyChristian RitzHarleen M. S. GrewalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John Espen Gjøen Synne Jenum Dhanasekaran Sivakumaran Aparna Mukherjee Ragini Macaden Sushil K. Kabra Rakesh Lodha Tom H. M. Ottenhoff Marielle C. Haks Timothy Mark Doherty Christian Ritz Harleen M. S. Grewal Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
description	Abstract Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood of Indian children, capable of discriminating intra-thoracic TB disease from other symptomatic illnesses. We investigated the expression of 198 genes in a training set, comprising 47 TB cases (19 definite/28 probable) and 36 asymptomatic household controls, and identified a 7- and a 10-transcript signature, both including NOD2, GBP5, IFITM1/3, KIF1B and TNIP1. The discriminatory abilities of the signatures were evaluated in a test set comprising 24 TB cases (17 definite/7 probable) and 26 symptomatic non-TB cases. In separating TB-cases from symptomatic non-TB cases, both signatures provided an AUC of 0.94 (95%CI, 0.88–1.00), a sensitivity of 91.7% (95%CI, 71.5–98.5) regardless of culture status, and 100% sensitivity for definite TB. The 7-transcript signature provided a specificity of 80.8% (95%CI, 60.0–92.7), and the 10-transcript signature a specificity of 88.5% (95%CI, 68.7–96.9%). Although warranting exploration and validation in other populations, our findings are promising and potentially relevant for future non-sputum based POC diagnostic tools for pediatric TB.
format	article
author	John Espen Gjøen Synne Jenum Dhanasekaran Sivakumaran Aparna Mukherjee Ragini Macaden Sushil K. Kabra Rakesh Lodha Tom H. M. Ottenhoff Marielle C. Haks Timothy Mark Doherty Christian Ritz Harleen M. S. Grewal
author_facet	John Espen Gjøen Synne Jenum Dhanasekaran Sivakumaran Aparna Mukherjee Ragini Macaden Sushil K. Kabra Rakesh Lodha Tom H. M. Ottenhoff Marielle C. Haks Timothy Mark Doherty Christian Ritz Harleen M. S. Grewal
author_sort	John Espen Gjøen
title	Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
title_short	Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
title_full	Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
title_fullStr	Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
title_full_unstemmed	Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
title_sort	novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e3c7dd1d08254a8dbb04f27f1e98da63
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Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children

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