| Popis: |
Here, we report the development of “DRonA” and “MLSynergy”, algorithms to perform rapid drug response assays and predict response of Mtb to novel drug combinations. Using a transcriptome signature for cell viability, DRonA accurately detects bacterial killing by diverse mechanisms in broth culture, macrophage infection and patient sputum, providing an efficient, and more sensitive alternative to time- and resource-intensive bacteriologic assays. Further, MLSynergy builds on DRonA to predict synergistic and antagonistic multi-drug combinations using transcriptomes of Mtb treated with single drugs. Together, DRonA and MLSynergy represent a generalizable framework for rapid monitoring of drug effects in host-relevant contexts and accelerate the discovery of efficacious high-order drug combinations. |
