Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children

Noton K. Dutta, Jeffrey A. Tornheim, Kiyoshi F. Fukutani, Mandar Paradkar, Rafael T. Tiburcio, Aarti Kinikar, Chhaya Valvi, Vandana Kulkarni, Neeta Pradhan, Shri Vijay Bala Yogendra Shivakumar, Anju Kagal, Akshay Gupte, Nikhil Gupte, Vidya Mave, Amita Gupta, Bruno B. Andrade, Petros C. Karakousis

Research output: Contribution to journalArticlepeer-review

Abstract

Pediatric tuberculosis (TB) remains a major global health problem. Improved pediatric diagnostics using readily available biosources are urgently needed. We used liquid chromatography-mass spectrometry to analyze plasma metabolite profiles of Indian children with active TB (n = 16) and age- and sex-matched, Mycobacterium tuberculosis-exposed but uninfected household contacts (n = 32). Metabolomic data were integrated with whole blood transcriptomic data for each participant at diagnosis and throughout treatment for drug-susceptible TB. A decision tree algorithm identified 3 metabolites that correctly identified TB status at distinct times during treatment. N-acetylneuraminate achieved an area under the receiver operating characteristic curve (AUC) of 0.66 at diagnosis. Quinolinate achieved an AUC of 0.77 after 1 month of treatment, and pyridoxate achieved an AUC of 0.87 after successful treatment completion. A set of 4 metabolites (gamma-glutamylalanine, gamma-glutamylglycine, glutamine, and pyridoxate) identified treatment response with an AUC of 0.86. Pathway enrichment analyses of these metabolites and corresponding transcriptional data correlated N-acetylneuraminate with immunoregulatory interactions between lymphoid and non-lymphoid cells, and correlated pyridoxate with p53-regulated metabolic genes and mitochondrial translation. Our findings shed new light on metabolic dysregulation in children with TB and pave the way for new diagnostic and treatment response markers in pediatric TB.

Original languageEnglish (US)
Article number19527
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • General

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