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

Detalhes bibliográficos
Autor(a) principal: Dutta, Noton K.
Data de Publicação: 2020
Outros Autores: 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.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/45817
Resumo: 1Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, 1551 East Jefferson Street, Room 110, Baltimore, MD 21287, USA. 2Center for Clinical Global Health Education, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3Laboratório de Inflamação E Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. 5Curso de Medicina, Faculdade de Tecnologia E Ciências, Salvador, Brazil. 6Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India. 7Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, India. 8Johns Hopkins University - India Office (CCGHE), Pune, Maharashtra, India. 9Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil. 10Escola Bahiana de Medicina E Saúde Pública (EBMSP), Salvador, Brazil. 11Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 12These authors contributed equally: Noton K. Dutta, Jeffrey A. Tornheim, Kiyoshi F. Fukutani, Mandar Paradkar, Bruno B. Andrade and Petros C. Karakousis. *email: notonkumardutta@gmail.com; petros@jhmi.edu
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spelling Dutta, Noton K.Tornheim, Jeffrey A.Fukutani, Kiyoshi FerreiraParadkar, MandarTiburcio, Rafael T.Kinikar, AartiValvi, ChhayaKulkarni, VandanaPradhan, NeetaShivakumar, Shri Vijay Bala YogendraKagal, AnjuGupte, AkshayGupte, NikhilMave, VidyaGupta, AmitaAndrade, Bruno de BezerrilKarakousis, Petros C.2021-01-26T11:17:38Z2021-01-26T11:17:38Z2020DUTTA, Noton K. et al. Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children. Scientific Reports, 2020.2045-2322https://www.arca.fiocruz.br/handle/icict/4581710.1038/s41598-020-75513-81Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, 1551 East Jefferson Street, Room 110, Baltimore, MD 21287, USA. 2Center for Clinical Global Health Education, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3Laboratório de Inflamação E Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. 5Curso de Medicina, Faculdade de Tecnologia E Ciências, Salvador, Brazil. 6Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India. 7Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, India. 8Johns Hopkins University - India Office (CCGHE), Pune, Maharashtra, India. 9Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil. 10Escola Bahiana de Medicina E Saúde Pública (EBMSP), Salvador, Brazil. 11Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 12These authors contributed equally: Noton K. Dutta, Jeffrey A. Tornheim, Kiyoshi F. Fukutani, Mandar Paradkar, Bruno B. Andrade and Petros C. Karakousis. *email: notonkumardutta@gmail.com; petros@jhmi.edu"Múltipla ver em Notas"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.engNature ResearchTuberculoseCriançasBiomarcadoresDiagnósticoMycobacterium tuberculosisTratamentoTuberculosisChildrenBiomarkersDiagnosisMycobacterium tuberculosisTreatmentIntegration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in childreninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/45817/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALDutta, K Noton. Integration...pdfDutta, K Noton. 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dc.title.pt_BR.fl_str_mv Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
title Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
spellingShingle Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
Dutta, Noton K.
Tuberculose
Crianças
Biomarcadores
Diagnóstico
Mycobacterium tuberculosis
Tratamento
Tuberculosis
Children
Biomarkers
Diagnosis
Mycobacterium tuberculosis
Treatment
title_short Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
title_full Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
title_fullStr Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
title_full_unstemmed Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
title_sort Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children
author Dutta, Noton K.
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv 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.
dc.subject.other.pt_BR.fl_str_mv Tuberculose
Crianças
Biomarcadores
Diagnóstico
Mycobacterium tuberculosis
Tratamento
topic Tuberculose
Crianças
Biomarcadores
Diagnóstico
Mycobacterium tuberculosis
Tratamento
Tuberculosis
Children
Biomarkers
Diagnosis
Mycobacterium tuberculosis
Treatment
dc.subject.en.pt_BR.fl_str_mv Tuberculosis
Children
Biomarkers
Diagnosis
Mycobacterium tuberculosis
Treatment
description 1Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, 1551 East Jefferson Street, Room 110, Baltimore, MD 21287, USA. 2Center for Clinical Global Health Education, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3Laboratório de Inflamação E Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil. 4Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil. 5Curso de Medicina, Faculdade de Tecnologia E Ciências, Salvador, Brazil. 6Byramjee Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India. 7Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, India. 8Johns Hopkins University - India Office (CCGHE), Pune, Maharashtra, India. 9Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil. 10Escola Bahiana de Medicina E Saúde Pública (EBMSP), Salvador, Brazil. 11Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 12These authors contributed equally: Noton K. Dutta, Jeffrey A. Tornheim, Kiyoshi F. Fukutani, Mandar Paradkar, Bruno B. Andrade and Petros C. Karakousis. *email: notonkumardutta@gmail.com; petros@jhmi.edu
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2021-01-26T11:17:38Z
dc.date.available.fl_str_mv 2021-01-26T11:17:38Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv DUTTA, Noton K. et al. Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children. Scientific Reports, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45817
dc.identifier.issn.pt_BR.fl_str_mv 2045-2322
dc.identifier.doi.none.fl_str_mv 10.1038/s41598-020-75513-8
identifier_str_mv DUTTA, Noton K. et al. Integration of metabolomics and transcriptomics reveals novel biomarkers in the blood for tuberculosis diagnosis in children. Scientific Reports, 2020.
2045-2322
10.1038/s41598-020-75513-8
url https://www.arca.fiocruz.br/handle/icict/45817
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language eng
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dc.publisher.none.fl_str_mv Nature Research
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