A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection [Berry_South Africa]

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. 43 of the 47 samples in this series were re-analyzed from GSE19442. These samples include links to the original sample at the foot of the page.

已有研究报道了可区分活动性结核病患者与无症状潜伏感染者的全血转录特征，但目前尚无共识确定最优的精简基因集组成，以作为同时具备区分其他疾病能力的诊断生物标志物。我们对早期Berry等人2010年的队列（GSE19444与GSE19442）进行了RNA测序（RNA Sequencing，RNA-Seq），并分别在英国莱斯特针对新发结核病患者与近期结核病接触者这两个受试者群体，建立了前瞻性队列研究。在莱斯特队列中，我们首先开展了系统性纵向采样与临床表征工作，以期在一组全新的独立队列（包含活动性结核病患者与潜伏结核感染（Latent Tuberculosis Infection，LTBI）个体）中，通过RNA-Seq验证我们的结核病特征；其次旨在为低结核病发病率地区提供纵向研究数据。本系列的47份样本中有43份来自GSE19442并进行了重新分析。页面底部提供了这些样本与原始样本的关联链接。