Transcriptomic Profiles of Confirmed Pediatric Tuberculosis Patients and Household Contacts Identifies Active Tuberculosis, Infection, and Treatment Response Among Indian Children.

Autor:	Tornheim JA; Center for Clinical Global Health Education, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Madugundu AK; Institute of Bioinformatics, Bangalore, Karnataka, India.; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.; Department of Laboratory Medicine and Pathology and Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Paradkar M; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Fukutani KF; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil.; Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil., Queiroz ATL; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil., Gupte N; Center for Clinical Global Health Education, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Gupte AN; Center for Clinical Global Health Education, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Kinikar A; Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, India., Kulkarni V; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Balasubramanian U; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Sreenivasamurthy S; Institute of Bioinformatics, Bangalore, Karnataka, India.; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Raja R; Institute of Bioinformatics, Bangalore, Karnataka, India.; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India., Pradhan N; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Shivakumar SVBY; Johns Hopkins University - India office (Center for Clinical Global Health Education), Pune, Maharashtra, India., Valvi C; Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, India., Hanna LE; National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India., Andrade BB; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil.; Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil.; Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil.; Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil., Mave V; Center for Clinical Global Health Education, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India., Pandey A; Institute of Bioinformatics, Bangalore, Karnataka, India.; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.; Department of Laboratory Medicine and Pathology and Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Gupta A; Center for Clinical Global Health Education, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2020 Apr 27; Vol. 221 (10), pp. 1647-1658.
DOI:	10.1093/infdis/jiz639
Abstrakt:	Background: Gene expression profiling is emerging as a tool for tuberculosis diagnosis and treatment response monitoring, but limited data specific to Indian children and incident tuberculosis infection (TBI) exist. Methods: Sixteen pediatric Indian tuberculosis cases were age- and sex-matched to 32 tuberculosis-exposed controls (13 developed incident TBI without subsequent active tuberculosis). Longitudinal samples were collected for ribonucleic acid sequencing. Differential expression analysis generated gene lists that identify tuberculosis diagnosis and tuberculosis treatment response. Data were compared with published gene lists. Population-specific risk score thresholds were calculated. Results: Seventy-one genes identified tuberculosis diagnosis and 25 treatment response. Within-group expression was partially explained by age, sex, and incident TBI. Transient changes in gene expression were identified after both infection and treatment. Application of 27 published gene lists to our data found variable performance for tuberculosis diagnosis (sensitivity 0.38-1.00, specificity 0.48-0.93) and treatment response (sensitivity 0.70-0.80, specificity 0.40-0.80). Our gene lists found similarly variable performance when applied to published datasets for diagnosis (sensitivity 0.56-0.85, specificity 0.50-0.85) and treatment response (sensitivity 0.49- 0.86, specificity 0.50-0.84). Conclusions: Gene expression profiles among Indian children with confirmed tuberculosis were distinct from adult-derived gene lists, highlighting the importance of including distinct populations in differential gene expression models. (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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