TY - JOUR
T1 - Transcriptomic Profiles of Confirmed Pediatric Tuberculosis Patients and Household Contacts Identifies Active Tuberculosis, Infection, and Treatment Response among Indian Children
AU - Tornheim, Jeffrey A.
AU - Madugundu, Anil K.
AU - Paradkar, Mandar
AU - Fukutani, Kiyoshi F.
AU - Queiroz, Artur T.L.
AU - Gupte, Nikhil
AU - Gupte, Akshay N.
AU - Kinikar, Aarti
AU - Kulkarni, Vandana
AU - Balasubramanian, Usha
AU - Sreenivasamurthy, Sreelakshmi
AU - Raja, Remya
AU - Pradhan, Neeta
AU - Shivakumar, Shri Vijay Bala Yogendra
AU - Valvi, Chhaya
AU - Hanna, Luke Elizabeth
AU - Andrade, Bruno B.
AU - Mave, Vidya
AU - Pandey, Akhilesh
AU - Gupta, Amita
N1 - Publisher Copyright:
© 2020 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/4/27
Y1 - 2020/4/27
N2 - 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.
AB - 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.
KW - India
KW - TB diagnosis
KW - pediatric TB
KW - transcriptomics
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U2 - 10.1093/infdis/jiz639
DO - 10.1093/infdis/jiz639
M3 - Article
C2 - 31796955
AN - SCOPUS:85091013909
SN - 0022-1899
VL - 221
SP - 1647
EP - 1658
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -