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Prognostic performance of both signatures was validated in an independent cohort of 1,948 HIV-negative household TB contacts from The Gambia (aged 15–60 years, 66% female), longitudinally followed up for 2 years between Maand October 21, 2010, sampled at baseline, month 6, and month 18.
#STERLING TRIPOD BETA FULL#
Poor performance on samples 13–24 months before TB diagnosis motivated discovery of a second 3-protein signature, 3-protein pair-ratio (3PR) developed using an orthogonal strategy on the full ACS subcohort. A 5-protein signature, TB Risk Model 5 (TRM5), was discovered in the ACS training set and verified by blind prediction in the ACS test set.
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Three hundred sixty-one proteins of differential abundance between progressors and nonprogressors were identified. Over 3,000 human proteins were quantified in plasma with a highly multiplexed proteomic assay (SOMAscan). Forty-six individuals developed microbiologically confirmed TB disease within 2 years of follow-up and were selected as progressors 106 nonprogressors, who remained healthy, were matched to progressors. Proteomic TB risk signatures were discovered in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents aged 12–18 years (68% female) who participated in the Adolescent Cohort Study (ACS) between Jand April 23, 2007, through either active (every 6 months) or passive follow-up over 2 years. Scriba, Conceptualization, Funding acquisition, Methodology, Resources, Supervision, Writing – original draft, Writing – review & editing, 1, * and ACS and GC6–74 cohort study groups ¶ Zak, Conceptualization, Data curation, Formal analysis, Funding acquisition, Supervision, Writing – review & editing, 3 Thomas J. Kaufmann, Conceptualization, Data curation, Funding acquisition, Project administration, Supervision, Writing – review & editing, 4 Jayne Sutherland, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing, 5 Gerhard Walzl, Data curation, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing – review & editing, 6 Mary Ann De Groote, Formal analysis, Supervision, Writing – original draft, Writing – review & editing, 2 Urs Ochsner, Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Writing – review & editing, 2 Daniel E. Hanekom, Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – review & editing, 1 Nebojsa Janjic, Formal analysis, Project administration, Writing – review & editing, 2 Mark Hatherill, Funding acquisition, Investigation, Supervision, Writing – review & editing, 1 Stefan H. Wall, Data curation, Methodology, Project administration, Writing – review & editing, 2 Michelle Fisher, Investigation, Project administration, Writing – review & editing, 1 Sara Suliman, Data curation, Project administration, Writing – review & editing, 1 Smitha Shankar, Formal analysis, Writing – review & editing, 3 Willem A. Thompson, Data curation, Formal analysis, Methodology, Writing – review & editing, # 3 David Sterling, Data curation, Formal analysis, Methodology, Writing – review & editing, 2 Stanley Kimbung Mbandi, Data curation, Formal analysis, Methodology, Writing – review & editing, 1 Kirsten M. Adam Penn-Nicholson, Conceptualization, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing, # 1 Thomas Hraha, Data curation, Formal analysis, Methodology, Writing – review & editing, # 2 Ethan G.