The TB27 Transcriptomic Model for Predicting Mycobacterium tuberculosis Culture Conversion
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Abstract
Rationale: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.
Objective: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.
Methods: Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.
Results: The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of 27 genes (TB27) for predicting the remaining time to culture conversion (TCC) at any given time. In the test dataset, predicted TCC and observed TCC achieved a correlation coefficient of r=0.98. An external validation cohort of 34 patients shows a correlation between predicted and observed days to TCC also of r=0.98.
Conclusion: We identified and validated a whole blood-based RNA signature (TB27) that demonstrates an excellent agreement between predicted and observed times to M. tuberculosis culture conversion during tuberculosis therapy. TB27 is a potential useful biomarker for anti-tuberculosis drug development and for prediction of treatment responses in clinical practice.
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