Blood Transcriptional Profiles of Active and Latent TB (UK Test Set)

This dataset aims to validate and confirm the signature identified in the training set. The aim of the experiment was to define transcriptional signatures in whole blood of TB patients (before drug treatment) and healthy controls to distinguish the signature of Latent and Active TB patients from each other and from healthy controls. This will help in diagnosis of active tuberculosis which normally relies on culture of the bacilli, which can take up to 6 wks, and sometimes the bacilli cannot be obtained from sputum thus requiring invasive techniques obtaining bronchoalveolar lavage (BAL). In some cases the bacill cannot be grown from sputum or BAL. Secondly the aim was to determine whether Latent patients have a homogeneous or heterogeneous signature, one may expect the latter since it is not possible to determine by the present tests (Tuberculin skin test - TST - or MTb antigen responsiveness of blood cells to produce IFN-gamma - IGRA assay) whether the mycobacteria has been cleared, is still present but is controlled, or if patients are recently infected or reactivated and will develop active TB. Experimental design : Whole blood collected in tempus tubes from patients with different spectra of TB disease and healthy controls. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum or bronchoalvelolar lavage fluid. Latent TB: LTB - All patients were screened at a tuberculosis clinic, being either new entrants to the UK from endemic countries or being household contacts of infectious cases. All were positive by tuberculin skin test (>14mm if BCG vaccinated, >5mm if not vaccinated) and were also positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Latent patients had no clinical, radiological or microbiological evidence of active infection and were asymptomatic. Healthy controls - these were volunteers without exposure to TBwho were negative by both tuberculin skin test (<15mm if BCG vaccinated, <6mm if unvaccinated); who were also negative by IGRA (as described above). This dataset: PTB, n= 21. LTB, n = 21. BCG+, n = 12. Experimental variables : Patient group: Active PTB; Latent TB, Healthy controls (BCG vaccinated only). ethnicity - a wide range of ethnic groups is represented. The active PTB group incorporates a range of smear positive and smear negative disease and a spectrum of disease extent/severity.

本数据集旨在验证并确认训练集所鉴定得到的转录特征标记。本实验的目标是在药物治疗前的结核病（Tuberculosis, TB）患者全血样本与健康对照中，定义转录特征标记，以区分潜伏性结核（Latent TB, LTB）患者、活动性结核（Active TB, ATB）患者与健康对照各自的特征标记。

该研究将助力活动性肺结核的临床诊断：当前活动性结核的常规诊断依赖于病原菌培养，该流程最长需6周，且有时无法从痰液中分离到结核分枝杆菌，此时需采用侵入性技术获取支气管肺泡灌洗液（Bronchoalveolar Lavage, BAL）；部分病例甚至无法从痰液或BAL中培养出结核分枝杆菌。其次，本实验旨在明确潜伏性结核患者的特征标记是否具有均一性，可预期其应为异质性，因为当前的检测手段（结核菌素皮肤试验Tuberculin Skin Test, TST，或γ干扰素释放试验Interferon-Gamma Release Assay, IGRA，即检测血液细胞针对结核分枝杆菌抗原产生γ干扰素的能力）无法区分以下情形：分枝杆菌已被清除、仍存在但处于受控状态，或是患者为新近感染、复燃并将发展为活动性结核。

实验设计：采用Tempus采血管采集不同病程阶段的结核病患者及健康对照的全血样本。所有患者均在接受抗分枝杆菌治疗前完成采样。
1. 活动性肺结核（Active Pulmonary TB, PTB）：所有患者均经痰液或支气管肺泡灌洗液培养分离到结核分枝杆菌（Mycobacterium Tuberculosis）而确诊。
2. 潜伏性结核（Latent TB, LTB）组：所有受试者均于结核病门诊完成筛查，包括来自结核流行国家的英国新入境人员，或传染性结核病例的家庭密切接触者。所有受试者结核菌素皮肤试验结果呈阳性（卡介苗接种者硬结直径>14mm，未接种者>5mm），且γ干扰素释放试验结果亦为阳性，具体检测采用澳大利亚Cellestis公司生产的Quantiferon Gold In-Tube检测试剂盒。潜伏性结核患者无活动性感染的临床、影像学或微生物学证据，且无相关临床症状。
3. 健康对照组：均为未接触过结核分枝杆菌的志愿者，结核菌素皮肤试验结果呈阴性（卡介苗接种者硬结直径<15mm，未接种者<6mm），且γ干扰素释放试验结果亦为阴性（检测方法同上）。

本数据集样本分组及样本量如下：活动性肺结核组（PTB），n=21；潜伏性结核组（LTB），n=21；卡介苗接种健康对照组（BCG+），n=12。

实验变量包括：受试者分组（活动性肺结核、潜伏性结核、仅接种过卡介苗的健康对照）；种族：本数据集涵盖多个不同种族群体。活动性肺结核组包含痰涂片阳性及痰涂片阴性的病例，且疾病范围与严重程度跨度较大。