Whole-Blood 3-Gene Signature as a Decision Aid for Rifapentine-based Tuberculosis Preventive Therapy

Hung Ling Huang, Jung Yu Lee, Yu Shu Lo, I. Hsin Liu, Sing Han Huang, Yu Wei Huang, Meng Rui Lee, Chih Hsin Lee, Meng Hsuan Cheng, Po Liang Lu, Jann Yuan Wang, Jinn Moon Yang, Inn Wen Chong

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1 引文 斯高帕斯(Scopus)

摘要

BACKGROUND: Systemic drug reaction (SDR) is a major safety concern with weekly rifapentine plus isoniazid for 12 doses (3HP) for latent tuberculosis infection (LTBI). Identifying SDR predictors and at-risk participants before treatment can improve cost-effectiveness of the LTBI program. METHODS: We prospectively recruited 187 cases receiving 3HP (44 SDRs and 143 non-SDRs). A pilot cohort (8 SDRs and 12 non-SDRs) was selected for generating whole-blood transcriptomic data. By incorporating the hierarchical system biology model and therapy-biomarker pathway approach, candidate genes were selected and evaluated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Then, interpretable machine learning models presenting as SHapley Additive exPlanations (SHAP) values were applied for SDR risk prediction. Finally, an independent cohort was used to evaluate the performance of these predictive models. RESULTS: Based on the whole-blood transcriptomic profile of the pilot cohort and the RT-qPCR results of 2 SDR and 3 non-SDR samples in the training cohort, 6 genes were selected. According to SHAP values for model construction and validation, a 3-gene model for SDR risk prediction achieved a sensitivity and specificity of 0.972 and 0.947, respectively, under a universal cutoff value for the joint of the training (28 SDRs and 104 non-SDRs) and testing (8 SDRs and 27 non-SDRs) cohorts. It also worked well across different subgroups. CONCLUSIONS: The prediction model for 3HP-related SDRs serves as a guide for establishing a safe and personalized regimen to foster the implementation of an LTBI program. Additionally, it provides a potential translational value for future studies on drug-related hypersensitivity.
原文英語
頁(從 - 到)743-752
頁數10
期刊Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
75
發行號5
DOIs
出版狀態已發佈 - 9月 14 2022

ASJC Scopus subject areas

  • 微生物學(醫學)
  • 傳染性疾病

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