{
  "abstract": "Background The prompt and precise diagnosis of active pulmonary tuberculosis (TB) is crucial for controlling this disease and yet it remains a global challenge. The objective of this study was to identify a set of microRNAs (miRNAs) whose expression in plasma could be used as a triage test for diagnosing TB.Methods A total of 879 plasma samples were collected in seven clinical centres from healthy individuals and patients displaying TB-like symptoms and/or radiological features consistent with TB. The samples were classified as TB, pneumonia, lung cancer and HC subgroups based on subsequent diagnostic assessments.We performed quantitative profiling of 264 plasma miRNAs in a training cohort (n=410) and an independent external test cohort (n=469). After dimensionality reduction and feature selection analysis, we identified nine discriminative miRNAs and used them to train an ensemble model in a training cohort using the scikit-learn library, which was subsequently evaluated in the external test cohort.Results The ensemble model showed notable accuracy in discriminating TB from non-TB patients, yielding areas under the curve (AUC) of 0.84 (95% CI 0.80 to 0.88) for the training cohort and 0.86 (95% CI 0.82 to 0.90) for the external test cohort. When tested against subgroups of laboratory confirmed and clinically diagnosed but unconfirmed TB, the AUC values were 0.89 (95% CI 0.85 to 0.93) and 0.83 (95% CI 0.79 to 0.88), respectively. In smear-negative confirmed TB patients, the AUC exceeded 0.83, with a sensitivity and specificity of 0.75.Conclusions Our miRNA ensemble model, based on detecting a nine-miRNA expression biosignature in plasma, demonstrated promising ability to diagnose TB and distinguish it from other common lung diseases but further studies are needed to assess its clinical applicability.Trial registration number ChiCTR2000039734.",
  "authors": [
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China",
        "Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, China"
      ],
      "name": "Yunlong Hu"
    },
    {
      "affiliations": [
        "Infectious Diseases Center, Guangzhou Eighth People’s Hospital, Guangzhou, Guangdong, China"
      ],
      "name": "Huihua Zhang"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China"
      ],
      "name": "Yuzhong Xu"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China"
      ],
      "name": "Hao Yang"
    },
    {
      "affiliations": [
        "Infectious Diseases Center, Guangzhou Eighth People’s Hospital, Guangzhou, Guangdong, China"
      ],
      "name": "Qing Yu"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Ningjian Cai"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Jinjin Xu"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Yue Zhang"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Da Liu"
    },
    {
      "affiliations": [
        "Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Kang Kang"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Siwei Mo"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Sinan Li"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Jingjia Zhang"
    },
    {
      "affiliations": [
        "The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, Suzhou, People's Republic of China"
      ],
      "name": "Peijun Tang"
    },
    {
      "affiliations": [
        "Guangzhou Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, People's Republic of China"
      ],
      "name": "Yaoju Tan"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, Ganzhou Fifth People's Hospital, The Ninth Affiliated Clinical College of Gannan Medical University, Ganzhou, People's Republic of China"
      ],
      "name": "Jiang Zeng"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China"
      ],
      "name": "Tianyu Zhong"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Infectious Diseases, Guangdong Key Lab for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People's Republic of China"
      ],
      "name": "Qianting Yang"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China",
        "National Clinical Research Center for Infectious Diseases, Guangdong Key Lab for Diagnosis and Treatment of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People's Republic of China"
      ],
      "name": "Wenfei Wang"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Dayong Gu"
    },
    {
      "affiliations": [
        "Laboratory of Molecular Biology, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China"
      ],
      "name": "Chuanzhi Zhu"
    },
    {
      "affiliations": [
        "Infectious Diseases Center, Guangzhou Eighth People’s Hospital, Guangzhou, Guangdong, China"
      ],
      "name": "Yuping Ning"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China"
      ],
      "name": "Kehong Zhang"
    },
    {
      "affiliations": [
        "Infectious Diseases Center, Guangzhou Eighth People’s Hospital, Guangzhou, Guangdong, China"
      ],
      "name": "Youchao Dai"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Chenyan Shi"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Dachuan Lin"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, China"
      ],
      "name": "Ling Ji"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Yi Cai"
    },
    {
      "affiliations": [
        "Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Deming Gou"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, People's Republic of China"
      ],
      "name": "Xinchun Chen"
    }
  ],
  "title": "Plasma miRNA signature for the diagnosis of pulmonary tuberculosis in symptomatic patients",
  "uid": "566c5eed-9596-5164-a485-65f7b608c898"
}