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...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2017-07-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-05057-x |
id |
doaj-e3c7dd1d08254a8dbb04f27f1e98da63 |
---|---|
record_format |
Article |
spelling |
doaj-e3c7dd1d08254a8dbb04f27f1e98da632020-12-08T01:24:46ZengNature Publishing GroupScientific Reports2045-23222017-07-01711910.1038/s41598-017-05057-xNovel transcriptional signatures for sputum-independent diagnostics of tuberculosis in childrenJohn Espen Gjøen0Synne Jenum1Dhanasekaran Sivakumaran2Aparna Mukherjee3Ragini Macaden4Sushil K. Kabra5Rakesh Lodha6Tom H. M. Ottenhoff7Marielle C. Haks8Timothy Mark Doherty9Christian Ritz10Harleen M. S. Grewal11Department of Clinical Science, Faculty of Medicine, University of BergenDepartment of Clinical Science, Faculty of Medicine, University of BergenDepartment of Clinical Science, Faculty of Medicine, University of BergenDepartment of Pediatrics, All India Institute of Medical SciencesDivision of Infectious Diseases, St. John’s Research InstituteDepartment of Pediatrics, All India Institute of Medical SciencesDepartment of Pediatrics, All India Institute of Medical SciencesDepartment of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical CenterDepartment of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical CenterGlaxoSmithKline VaccinesDepartment of Nutrition, Exercise and Sports, University of CopenhagenDepartment of Clinical Science, Faculty of Medicine, University of BergenAbstract 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.https://doi.org/10.1038/s41598-017-05057-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-05057-x |
work_keys_str_mv |
AT johnespengjøen noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT synnejenum noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT dhanasekaransivakumaran noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT aparnamukherjee noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT raginimacaden noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT sushilkkabra noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT rakeshlodha noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT tomhmottenhoff noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT mariellechaks noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT timothymarkdoherty noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT christianritz noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren AT harleenmsgrewal noveltranscriptionalsignaturesforsputumindependentdiagnosticsoftuberculosisinchildren |
_version_ |
1724394958870282240 |