Whole blood transcriptional signatures distinguishing active tuberculosis patients from asymptomatic latently infected individuals exist. Consensus has not been achieved regarding the optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Here we show a blood transcriptional signature of active tuberculosis using RNA-Seq, confirming microarray results, that discriminates active tuberculosis from latently infected and healthy individuals, validating this signature in an independent cohort. Using an advanced modular approach, we utilise the information from the entire transcriptome, which includes overabundance of type I interferon-inducible genes and underabundance of IFNG and TBX21, to develop a signature that discriminates active tuberculosis patients from latently infected individuals or those with acute viral and bacterial infections. We suggest that methods targeting gene selection across multiple discriminant modules can improve the development of diagnostic biomarkers with improved performance. Finally, utilising the modular approach, we demonstrate dynamic heterogeneity in a longitudinal study of recent tuberculosis contacts.

中文翻译：

---

模块化转录特征可识别人类结核病感染的表型异质性。

存在区分活动性结核病患者和无症状潜伏感染个体的全血转录特征。关于将最佳减少基因集作为诊断生物标志物来区分其他疾病，尚未达成共识。在这里，我们使用 RNA-Seq 显示了活动性结核病的血液转录特征，确认了微阵列结果，将活动性结核病与潜伏感染者和健康个体区分开来，在独立队列中验证了该特征。使用先进的模块化方法，我们利用整个转录组的信息（包括 I 型干扰素诱导基因的过量和 IFNG 和 TBX21 的不足）来开发区分活动性结核病患者与潜伏感染者或急性病毒感染者的特征和细菌感染。我们建议跨多个判别模块的针对基因选择的方法可以改善诊断生物标志物的开发并提高性能。最后，利用模块化方法，我们在近期结核病接触者的纵向研究中证明了动态异质性。