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

ABSTRACT:

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

SUBMITTER: Huang HL 

PROVIDER: S-EPMC9477448 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature