Blood-based TB precision medicine: transcriptomic model estimates time to culture conversion

Reference Number TO 14-00169

Keywords

tuberculosis (TB), MDR-TB, XDR-TB, transcriptomic analysis, whole blood, culture conversion, treatment response, drug development

Invention Novelty

Tuberculosis (TB), including drug-resistant TB, remains a major global health challenge. Monitoring treatment response is difficult: sputum culture can take weeks, and suitable sputum samples are not available for every patient or at every time point. The innovation is a 27-gene, whole-blood transcriptomic model that estimates the remaining time to Mycobacterium tuberculosis culture conversion during treatment. It is designed to provide a host-response-based estimate of a microbiological treatment milestone, not to replace culture.

Value Proposition

TB27 estimates the time remaining until culture conversion from whole-blood gene-expression data collected during TB treatment. The approach can complement conventional microbiological monitoring and could be valuable in TB drug-development studies, where timely assessment of treatment response is important. In the reported test and independent validation datasets, predicted and observed time to culture conversion were highly correlated.

Technology Description

TB27 was developed using longitudinal whole-blood RNA-expression and clinical data from patients with DS-TB and MDR-TB. Blood samples were collected at defined time points during treatment and analyzed using gene-expression microarrays. A multi-step modelling approach combined estimates of bacterial burden and clearance with gene-expression data and time on treatment to predict the remaining days until culture conversion. The final model comprises 27 gene targets.

The identification cohort included 149 patients and was split into training and test datasets; an independent validation cohort included 34 patients. In the test and external validation datasets, the correlation between predicted and observed time to culture conversion was r=0.98. The median difference between observed and predicted remaining time was 1.7 days in the test dataset and 7.4 days in the external validation cohort.

Commercial Opportunity

TB27 is available for co-development and in-licensing, for example for assay development, further clinical validation or evaluation as a biomarker in TB drug-development studies.

Development Status

TB27 was evaluated in a held-out test dataset and in an independent cohort of 34 patients. In the reported datasets, it predicted remaining time to culture conversion more closely than the published signatures included in the study for that specific analysis. Further validation is currently performed.