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https://www.arca.fiocruz.br/handle/icict/45817
INTEGRATION OF METABOLOMICS AND TRANSCRIPTOMICS REVEALS NOVEL BIOMARKERS IN THE BLOOD FOR TUBERCULOSIS DIAGNOSIS IN CHILDREN
Crianças
Biomarcadores
Diagnóstico
Mycobacterium tuberculosis
Tratamento
Author
Dutta, Noton K.
Tornheim, Jeffrey A.
Fukutani, Kiyoshi Ferreira
Paradkar, Mandar
Tiburcio, Rafael T.
Kinikar, Aarti
Valvi, Chhaya
Kulkarni, Vandana
Pradhan, Neeta
Shivakumar, Shri Vijay Bala Yogendra
Kagal, Anju
Gupte, Akshay
Gupte, Nikhil
Mave, Vidya
Gupta, Amita
Andrade, Bruno de Bezerril
Karakousis, Petros C.
Tornheim, Jeffrey A.
Fukutani, Kiyoshi Ferreira
Paradkar, Mandar
Tiburcio, Rafael T.
Kinikar, Aarti
Valvi, Chhaya
Kulkarni, Vandana
Pradhan, Neeta
Shivakumar, Shri Vijay Bala Yogendra
Kagal, Anju
Gupte, Akshay
Gupte, Nikhil
Mave, Vidya
Gupta, Amita
Andrade, Bruno de Bezerril
Karakousis, Petros C.
Affilliation
"Múltipla ver em Notas"
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 (gammaglutamylalanine,
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.
Keywords in Portuguese
TuberculoseCrianças
Biomarcadores
Diagnóstico
Mycobacterium tuberculosis
Tratamento
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