title: Utility of Novel Plasma Metabolic Markers in the Diagnosis of Pediatric Tuberculosis: A Classification and Regression Tree Analysis Approach.
abstract: Although tuberculosis (TB) has been the greatest killer due to a single infectious disease, pediatric TB is still hard to diagnose because of the lack of sensitive biomarkers. Metabolomics is increasingly being applied in infectious diseases. But little is known regarding metabolic biomarkers in children with TB. A combination of a NMR-based plasma metabolic method and classification and regression tree (CART) analysis was used to provide a broader range of applications in TB diagnosis in our study. Plasma samples obtained from 28 active TB children and 37 non-TB controls (including 21 RTIs and 16 healthy children) were analyzed by an orthogonal partial least-squares discriminant analysis (OPLS-DA) model, and 17 metabolites were identified that can separate children with TB from non-TB controls. CART analysis was then used to choose 3 of the markers, l-valine, pyruvic acid, and betaine, with the least error. The sensitivity, specificity, and area under the curve (AUC) of the 3 metabolites is 85.7% (24/28, 95% CI, 66.4%, 95.3%), 94.6% (35/37, 95% CI, 80.5%, 99.1%), and 0.984(95% CI, 0.917, 1.000), respectively. The 3 metabolites demonstrated sensitivity of 82.4% (14/17, 95% CI, 55.8%, 95.3%) and specificity of 83.9% (26/31, 95% CI, 65.5%, 93.9%), respectively, in 48 blinded subjects in an independent cohort. Taken together, the novel plasma metabolites are potentially useful for diagnosis of pediatric TB and would provide insights into the disease mechanism.
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Li
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Ren
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Dong
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Song
authors.affiliation: Key Laboratory of Major Diseases in Children, Ministry of Education, National Key Discipline of Pediatrics (Capital Medical University), Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University , 100045 Beijing, People's Republic of China.
authors.forename: A-Dong
authors.initials: AD
authors.lastname: Shen
mesh_terms: D001622:Betaine / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D016002:Discriminant Analysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D010949:Plasma / Q000378:metabolism; D019289:Pyruvic Acid / Q000032:analysis; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis*; D014633:Valine / Q000032:analysis
chemical_list: D015415:Biomarkers; D001622:Betaine; D019289:Pyruvic Acid; D014633:Valine
keywords: NMR; children; diagnosis; metabolomics; plasma; tuberculosis