Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.
Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.
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肺结核和肺外结核的血液转录组学诊断
DOI：
10.1172/jci.insight.87238
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发表时间：
2016-10-06
期刊：
影响因子：
8
通讯作者：
Noursadeghi M
中科院分区：
文献类型：
--
作者：
Roe JK;Thomas N;Gil E;Best K;Tsaliki E;Morris-Jones S;Stafford S;Simpson N;Witt KD;Chain B;Miller RF;Martineau A;Noursadeghi M
背景需要新的活动性结核病（TB）快速诊断方法来克服当前微生物检测的时间延迟和灵敏度不足，这些微生物检测严重依赖于疾病部位的采样。TB的多参数血液转录组学特征已被描述为潜在的诊断测试。我们试图确定作为活动性TB的宿主生物标志物的最佳转录候选物，通过与其他传染病的比较来扩展其特异性的评估，并测试其在肺和肺外TB中的表现。方法.将支持向量机学习与特征选择相结合，应用于新的和以前发表的血液转录谱，以识别多个患者队列（包括肺和肺外TB）以及有和没有HIV-1合并感染的个体共享的最小TB特异性转录特征。结果我们确定并验证了升高的血液碱性亮氨酸拉链转录因子2（BATF 2）转录水平作为区分活动性肺结核和肺外结核与健康个体的单一敏感生物标志物，在多个HIV-1阴性个体队列中，受试者操作特征（ROC）曲线下面积（AUC）评分为0.93至0.99，在HIV-1感染个体中为0.85。此外，我们鉴定并验证了一种潜在的新的4-基因签名，包括CD 177、触珠蛋白、免疫球蛋白J链和半乳糖凝集素10，其将活动性肺和肺外TB与其他发热性感染区分开，得到0.94至1的ROC AUC。结论.升高的血液BATF 2转录物水平提供了区分活动性TB与健康个体的敏感生物标志物，并且潜在的新的4基因转录特征在呈现发热的个体中区分活动性TB和其他感染性疾病。经费MRC、Wellcome Trust、Rosetrees Trust、British Lung Foundation、NIHR。血液BATF 2转录物为活动性结核病提供了一个单一的生物标志物，一个新的四基因转录特征将活动性结核病与其他发热感染性疾病区分开来。
BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR. Blood BATF2 transcripts provide a single biomarker for active tuberculosis and a novel four-gene transcriptional signature differentiates active TB from other infectious diseases with fever.
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