Efficient measurement and factorization of high-order drug interactions in Mycobacterium tuberculosis.
Sci Adv
; 3(10): e1701881, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-29026882
ABSTRACT
Combinations of three or more drugs are used to treat many diseases, including tuberculosis. Thus, it is important to understand how synergistic or antagonistic drug interactions affect the efficacy of combination therapies. However, our understanding of high-order drug interactions is limited because of the lack of both efficient measurement methods and theoretical framework for analysis and interpretation. We developed an efficient experimental sampling and scoring method [diagonal measurement of n-way drug interactions (DiaMOND)] to measure drug interactions for combinations of any number of drugs. DiaMOND provides an efficient alternative to checkerboard assays, which are commonly used to measure drug interactions. We established a geometric framework to factorize high-order drug interactions into lower-order components, thereby establishing a road map of how to use lower-order measurements to predict high-order interactions. Our framework is a generalized Loewe additivity model for high-order drug interactions. Using DiaMOND, we identified and analyzed synergistic and antagonistic antibiotic combinations against Mycobacteriumtuberculosis. Efficient measurement and factorization of high-order drug interactions by DiaMOND are broadly applicable to other cell types and disease models.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Testes de Sensibilidade Microbiana
/
Interações Medicamentosas
/
Mycobacterium tuberculosis
/
Antituberculosos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article