ArticleCell reports. Medicine2022
Design principles to assemble drug combinations for effective tuberculosis therapy using interpretable pairwise drug response measurements.
Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- MakingCell insight · 2026Review
- Dual inhibition of respiratory complexes inMicrobiology spectrum · 2026Article
- Strain diversity drives heterogeneous responses to tuberculosis combination therapy.Antimicrobial agents and chemotherapy · 2026Article
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- Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes.Nature microbiology · 2026Article
- Integrated omics reveal a unique antibacterial mechanism of action for the small molecule HSI#6.Current research in microbial sciences · 2026Article
- The eight pillars of within-host tuberculosis modelling.Frontiers in immunology · 2026Review
- Strain diversity drives heterogeneous responses to tuberculosis combination therapy.bioRxiv : the preprint server for biology · 2025Article
- Gut microbiota and tuberculosis.iMeta · 2025Review
- Article
- Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DeepDrug as an expert guided and AI driven drug repurposing methodology for selecting the lead combination of drugs for Alzheimer's disease.Scientific reports · 2025Article
- GEODE: anFrontiers in pharmacology · 2025Article
- Predicting fitness inFrontiers in tuberculosis · 2025Article
- Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.Nature communications · 2024Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.eLife · 2024Article
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.bioRxiv : the preprint server for biology · 2024Article
- Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A challenge in tuberculosis treatment regimen design is the necessity to combine three or more antibiotics. We narrow the prohibitively large search space by breaking down high-order drug combinations into drug pair units. Using pairwise in vitro measurements, we train machine learning models to predict higher-order combination treatment outcomes in the relapsing BALB/c mouse model. Classifiers perform well and predict many of the >500 possible combinations among 12 antibiotics to be improved over bedaquiline + pretomanid + linezolid, a treatment-shortening regimen compared with the standard of care in mice. We reformulate classifiers as simple rulesets to reveal guiding principles of constructing combination therapies for both preclinical and clinical outcomes. One example ruleset combines a drug pair that is synergistic in a dormancy model with a pair that is potent in a cholesterol-rich growth environment. These rulesets are predictive, intuitive, and practical, thus enabling rational construction of drug combinations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.