期刊
JOURNAL OF INFECTIOUS DISEASES
卷 221, 期 10, 页码 1647-1658出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz639
关键词
India; pediatric TB; TB diagnosis; transcriptomics
资金
- US National Institutes of Health (NIH)/Indian Department of Biotechnology (DBT) RePORT India Consortium
- Government of India's DBT
- Indian Council of Medical Research
- NIH, National Institute of Allergy and Infectious Diseases (NIAID), Office of AIDS Research
- Wellcome Trust/DBT India Alliance Margdarshi Fellowship [IA/M/15/1/502023]
- NIH NIAID [K23AI135102, R21AI122922, UM1AI069465]
- NIH Office of the Director, Fogarty International Center, Office of AIDS Research, National Cancer Center, National Heart, Blood, and Lung Institute
- NIH Office of Research for Women's Health through the Fogarty Global Health Fellows Program Consortium [R25TW009340]
- Johns Hopkins University School of Medicine Clinician Scientist Career Development Award
- Fogarty International Center BJGMC-JHU HIV-TB Program [D43TW009574]
- Ujala Foundation
- Gilead Foundation
- Wyncote Foundation
- Persistent Systems
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.
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