Integrative analysis of multimodal patient data identifies personalized predictors of tuberculosis treatment prognosis

Tuberculosis (TB) afflicted 10.6 million people in 2021, and its global burden is increasing due to multidrug-resistant TB (MDR-TB) and extensively resistant TB (XDR-TB). Here, we analyze multi-domain information from 5,060 TB patients spanning 10 countries with high burden of MDR-TB from the NIAID TB Portals database to determine predictors of TB treatment outcome. Our analysis revealed significant associations between radiological, microbiological, therapeutic, and demographic data modalities. Our machine learning model, built with 203 features across modalities outperforms models built using each modality alone in predicting treatment outcomes, with an accuracy of 83% and area under the curve of 0.84. Notably, our analysis revealed that the drug regimens Bedaquiline-Clofazimine-Cycloserine-Levofloxacin-Linezolid and Bedaquiline-Clofazimine-Linezolid-Moxifloxacin were associated with treatment success and failure, respectively, for MDR non-XDR-TB. Drug combinations predicted to be synergistic by the INDIGO algorithm performed better than antagonistic combinations. Our prioritized set of features predictive of treatment outcomes can ultimately guide the personalized clinical management of TB.