A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Leicester progressor]

Whole blood transcriptional signatures distinguishing patients with active tuberculosis from asymptomatic latently infected individuals have been described but, no consensus exists for the composition of optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. We undertook RNA Sequencing (RNA-Seq) of our earlier Berry et al. 2010 (GSE19444 and GSE19442) cohorts and additionally set up a prospective cohort study at Leicester (UK) in subject groups of incident TB and recent TB contacts, respectively. In the Leicester cohort, we performed systematic longitudinal sampling and clinical characterisation first, to validate our TB signature using RNA-Seq in a new and independent cohort of individuals with active TB and LTBI, and secondly to provide longitudinal data in a low TB incidence setting.