A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection.
A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection.
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DOI：
10.1038/s41467-018-04579-w
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发表时间：
2018-06-19
影响因子：
16.6
通讯作者：
O'Garra A
中科院分区：
文献类型：
--
作者：
Singhania A;Verma R;Graham CM;Lee J;Tran T;Richardson M;Lecine P;Leissner P;Berry MPR;Wilkinson RJ;Kaiser K;Rodrigue M;Woltmann G;Haldar P;O'Garra A
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标记。关于最佳减少的基因集作为诊断生物标志物，也实现了与其他疾病的区分，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，证实了微阵列结果，该结果将活动性结核病与潜伏感染和健康个体区分开来，并在独立队列中验证了该特征。使用先进的模块化方法，我们利用来自整个转录组的信息，其中包括I型干扰素诱导基因的过剩和IFNG和TBX 21的不足，以开发一种特征，将活动性结核病患者与潜伏感染者或急性病毒和细菌感染者区分开来。我们认为，针对多个判别模块的基因选择的方法可以改善诊断生物标志物的开发，提高性能。最后，利用模块化的方法，我们证明了动态异质性的纵向研究，最近的结核病接触。结核分枝杆菌的大规模筛查诊断存在，但这些工具的敏感性和特异性存在批评。在这里，作者使用RNA-Seq和模块化生物信息学方法，使用来自他们自己的队列的数据和对已发表队列的荟萃分析来创建用于检测结核病的简化签名，而不会检测到其他疾病。
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. Mass screening diagnostics for Mycobacterium tuberculosis exist, but criticisms exist regarding the sensitivity and specificity of these tools. Here the authors use RNA-Seq and a modular bioinformatics approach using data from their own cohorts and meta-analysis of published cohorts to create a reduced signature for detection of tuberculosis that does not detect other diseases.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
作者：
Esmail, Hanif;Lai, Rachel P.;Lesosky, Maia;Wilkinson, Katalin A.;Graham, Christine M.;Coussens, Anna K.;Oni, Tolu;Warwick, James M.;Said-Hartley, Qonita;Koegelenberg, Coenraad F.;Walzl, Gerhard;Flynn, JoAnne L.;Young, Douglas B.;Barry, Clifton E., III;O'Garra, Anne;Wilkinson, Robert J.
通讯作者：
Wilkinson, Robert J.
影响因子：
8.7
作者：
Cliff JM;Kaufmann SH;McShane H;van Helden P;O'Garra A
通讯作者：
O'Garra A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
15.9
作者：
Antonelli, Lis R. V.;Rothfuchs, Antonio Gigliotti;Sher, Alan
通讯作者：
Sher, Alan