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https://www.arca.fiocruz.br/handle/icict/39488
TRANSCRIPTOMIC PROFILES OF CONFIRMED PEDIATRIC TUBERCULOSIS PATIENTS AND HOUSEHOLD CONTACTS IDENTIFIES ACTIVE TUBERCULOSIS, INFECTION, AND TREATMENT RESPONSE AMONG INDIAN CHILDREN
Author
Tornheim, Jeffrey A.
Madugundu, Anil K.
Paradkar, Mandar
Fukutani, Kiyoshi Ferreira
Queiroz, Artur Trancoso Lopo de
Gupte, Nikhil
Gupte, Akshay N.
Kinikar, Aarti
Kulkarni, Vandana
Balasubramanian, Usha
Sreenivasamurthy, Sreelakshmi
Raja, Remya
Pradhan, Neeta
Shivakumar, Shri Vijay Bala Yogendra
Valvi, Chhaya
Hanna, Luke Elizabeth
Andrade, Bruno de Bezerril
Mave, Vidya
Pandey, Akhilesh
Gupta, Amita
Madugundu, Anil K.
Paradkar, Mandar
Fukutani, Kiyoshi Ferreira
Queiroz, Artur Trancoso Lopo de
Gupte, Nikhil
Gupte, Akshay N.
Kinikar, Aarti
Kulkarni, Vandana
Balasubramanian, Usha
Sreenivasamurthy, Sreelakshmi
Raja, Remya
Pradhan, Neeta
Shivakumar, Shri Vijay Bala Yogendra
Valvi, Chhaya
Hanna, Luke Elizabeth
Andrade, Bruno de Bezerril
Mave, Vidya
Pandey, Akhilesh
Gupta, Amita
Affilliation
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Manipal Academy of Higher Education. Manipal, Karnataka, India / Mayo Clinic. Center for Individualized Medicine. Department of Laboratory Medicine and Pathology Rochester. Minnesota, USA.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA
Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Johns Hopkins University School of Medicine. McKusick-Nathans Institute of Genetic Medicine. Baltimore, Maryland, USA.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Manipal Academy of Higher Education. Manipal, Karnataka, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University. India office Center for Clinical Global Health Education. Pune, Maharashtra, India.
Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
National Institute for Research in Tuberculosis. Chennai, Tamil Nadu, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities, Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Mayo Clinic. Center for Individualized Medicine. Department of Laboratory Medicine and Pathology Rochester. Minnesota, USA / Johns Hopkins University School of Medicine. McKusick-Nathans Institute of Genetic Medicine, , Baltimore, Maryland, USA.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins Bloomberg School of Public Health. Baltimore, Maryland, USA.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Manipal Academy of Higher Education. Manipal, Karnataka, India / Mayo Clinic. Center for Individualized Medicine. Department of Laboratory Medicine and Pathology Rochester. Minnesota, USA.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA
Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Johns Hopkins University School of Medicine. McKusick-Nathans Institute of Genetic Medicine. Baltimore, Maryland, USA.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Manipal Academy of Higher Education. Manipal, Karnataka, India.
Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Johns Hopkins University. India office Center for Clinical Global Health Education. Pune, Maharashtra, India.
Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
National Institute for Research in Tuberculosis. Chennai, Tamil Nadu, India.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities, Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, Maharashtra, India.
Institute of Bioinformatics. Bangalore, Karnataka, India / National Institute of Mental Health and Neurosciences Center for Molecular Medicine. Bangalore, India / Mayo Clinic. Center for Individualized Medicine. Department of Laboratory Medicine and Pathology Rochester. Minnesota, USA / Johns Hopkins University School of Medicine. McKusick-Nathans Institute of Genetic Medicine, , Baltimore, Maryland, USA.
Johns Hopkins University. School of Medicine. Center for Clinical Global Health Education. Division of Infectious Diseases. Baltimore, Maryland, USA / Johns Hopkins Bloomberg School of Public Health. Baltimore, Maryland, USA.
Abstract
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.
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