RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response
| Autor: | Penn-Nicholson, A, Mbandi, SK, Thompson, E, Mendelsohn, SC, Suliman, S, Chegou, NN, Malherbe, ST, Darboe, F, Erasmus, M, Hanekom, WA, Bilek, N, Fisher, M, Kaufmann, SHE, Winter, J, Murphy, M, Wood, R, Morrow, C, Van Rhijn, I, Moody, B, Murray, M, Andrade, BB, Sterling, TR, Sutherland, J, Naidoo, K, Padayatchi, N, Walzl, G, Hatherill, M, Zak, D, Scriba, TJ, Kafaar, F, Workman, L, Mulenga, H, Hughes, EJ, Xasa, O, Veldsman, A, Cloete, Y, Abrahams, D, Moyo, S, Gelderbloem, S, Tameris, M, Geldenhuys, H, Ehrlich, R, Verver, S, Geiter, L, Black, GF, van der Spuy, G, Stanley, K, Kriel, M, Du Plessis, N, Nene, N, Roberts, T, Kleynhans, L, Gutschmidt, A, Smith, B, Loxton, AG, Tromp, G, Tabb, D, Ottenhoff, THM, Klein, MR, Haks, MC, Franken, KLMC, Geluk, A, van Meijgaarden, KE, Joosten, SA, Boom, WH, Thiel, B, Mayanja-Kizza, H, Joloba, M, Zalwango, S, Nsereko, M, Okwera, B, Kisingo, H, Parida, SK, Golinski, R, Maertzdorf, J, Weiner, J, Jacobson, M, Dockrell, H, Smith, S, Gorak-Stolinska, P, Hur, YG, Lalor, M, Lee, JS, Crampin, AC, French, N, Ngwira, B, Ben-Smith, A, Watkins, K, Ambrose, L, Simukonda, F, Mvula, H, Chilongo, F, Saul, J, Branson, K, Mahomed, H, Downing, K |
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| Přispěvatelé: | The Adolescent Cohort Study team, The GC6-74 Consortium, The SATVI Clinical and Laboratory Team, The ScreenTB Consortium, The AE-TBC Consortium, The RePORT Brazil Team, Peruvian Household Contacts Cohort Team, The CAPRISA IMPRESS team, APH - Methodology, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, Global Health, AII - Infectious diseases, Translational Immunology Groningen (TRIGR) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Male GC6-74 Consortium AE-TBC Consortium lcsh:Medicine HIV Infections Disease Biomarkers/metabolism Lung/diagnostic imaging ScreenTB Consortium Cohort Studies Prognostic markers 0302 clinical medicine Immunopathology Peruvian Household Contacts Cohort Team CAPRISA IMPRESS team 030212 general & internal medicine lcsh:Science Lung Subclinical infection screening and diagnosis RNA Bacterial/metabolism Multidisciplinary Bacterial/metabolism Bacterial Prognosis Tuberculosis/complications RNA Bacterial Detection Infectious Diseases Mycobacterium tuberculosis/genetics Area Under Curve Cohort Biomarker (medicine) HIV/AIDS Female Adolescent Cohort Study team Infection Cohort study 4.2 Evaluation of markers and technologies RePORT Brazil Team medicine.medical_specialty Tuberculosis Adolescent Point-of-Care Systems HIV Infections/complications Real-Time Polymerase Chain Reaction/methods Real-Time Polymerase Chain Reaction Sensitivity and Specificity Article 03 medical and health sciences Rare Diseases Tuberculosis diagnosis Clinical Research Internal medicine medicine Humans business.industry SATVI Clinical and Laboratory Team Prevention lcsh:R Diagnostic markers Mycobacterium tuberculosis medicine.disease 4.1 Discovery and preclinical testing of markers and technologies 030104 developmental biology Good Health and Well Being ROC Curve Positron-Emission Tomography RNA lcsh:Q business Biomarkers |
| Zdroj: | Scientific reports Scientific reports, vol 10, iss 1 Scientific Reports Scientific reports, 10(1):8629. Nature Publishing Group Scientific Reports, Vol 10, Iss 1, Pp 1-21 (2020) Scientific Reports, 10(1). NATURE PUBLISHING GROUP Scientific Reports, 10(1). NLM (Medline) Scientific Reports, 10(1):8629. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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