Penn-Nicholson A, et al. - In this prospective cohort study, researchers attempted to develop a proteomic biomarker of risk of tuberculosis (TB) progression for ultimate translation into a point-of-care diagnostic. Through either active (every 6 months) or passive 2-year follow-up, proteomic TB risk signatures were found in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents (aged 12-18 years) who took an interest in the Adolescent Cohort Study between July 6, 2005, and April 23, 2007. Within a year of diagnosis, both proteomic TB risk signatures predicted progression to incident TB. These were the first proteomic prognostic signatures for TB that have been validated, though neither fulfill the minimum criteria described for a progression test in the WHO Target Product Profile. To develop such a test for the practical identification of individuals for the investigation of incipient, subclinical, or active TB disease for appropriate treatment and care, further work is required.