دورية أكاديمية
RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response
| العنوان: | RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response |
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| المؤلفون: | Penn-Nicholson, Adam, Mbandi, Stanley Kimbung, Thompson, Ethan, Mendelsohn, Simon C, Suliman, Sara, Chegou, Novel N, Malherbe, Stephanus T, Darboe, Fatoumatta, Erasmus, Mzwandile, Hanekom, Willem A, Bilek, Nicole, Fisher, Michelle, Kaufmann, Stefan H E, Winter, Jill, Murphy, Melissa, Wood, Robin, Morrow, Carl, Van Rhijn, Ildiko, Moody, Branch, Murray, Megan, Andrade, Bruno B, Sterling, Timothy R, Sutherland, Jayne, Naidoo, Kogieleum, Padayatchi, Nesri, Walzl, Gerhard, Hatherill, Mark, Zak, Daniel, Scriba, Thomas J |
| المصدر: | Adolescent Cohort Study team , Penn-Nicholson , A , Mbandi , S K , Thompson , E , Mendelsohn , S C , Suliman , S , Chegou , N N , Malherbe , S T , Darboe , F , Erasmus , M , Hanekom , W A , Bilek , N , Fisher , M , Kaufmann , S H E , Winter , J , Murphy , M , Wood , R , Morrow , C , Van Rhijn , I , Moody , B , Murray , M , Andrade , B B , Sterling .... |
| سنة النشر: | 2020 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Adolescent, Area Under Curve, Biomarkers/metabolism, Cohort Studies, Female, HIV Infections/complications, Humans, Lung/diagnostic imaging, Male, Mycobacterium tuberculosis/genetics, Point-of-Care Systems, Positron-Emission Tomography, Prognosis, RNA, Bacterial/metabolism, ROC Curve, Real-Time Polymerase Chain Reaction/methods, Sensitivity and Specificity, Tuberculosis/complications |
| الوصف: | Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/295e1c00-c25f-44c6-98e2-193cab6421ecTest |
| DOI: | 10.1038/s41598-020-65043-8 |
| الإتاحة: | https://doi.org/10.1038/s41598-020-65043-8Test https://hdl.handle.net/11370/295e1c00-c25f-44c6-98e2-193cab6421ecTest https://research.rug.nl/en/publications/295e1c00-c25f-44c6-98e2-193cab6421ecTest https://pure.rug.nl/ws/files/168496325/s41598_020_65043_8.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.58E85329 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-020-65043-8 |
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