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The seminal observation that blood transcriptomic changes can predate diagnosis of active tuberculosis set the field on a course to evaluate their potential impact as screening tools for early detection of disease. Early detection would allow prompt treatment initiation, which could permit shorter courses of therapy and reduce morbidity, mortality, and onward transmission of infection. In the study published by The Lancet Global Health, Simon C Mendelsohn and colleagues make an important contribution to the field by assessing the diagnostic accuracy and prognostic ability of an 11-gene transcriptomic signature (RISK11) among people living with HIV in South Africa.