A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.
Commun Biol
; 3(1): 747, 2020 12 21.
Article
en En
| MEDLINE
| ID: mdl-33349640
ABSTRACT
Approximately 10% of the world's population is at risk of schistosomiasis, a disease of poverty caused by the Schistosoma parasite. To facilitate drug discovery for this complex flatworm, we developed an automated high-content screen to quantify the multidimensional responses of Schistosoma mansoni post-infective larvae (somules) to chemical insult. We describe an integrated platform to process worms at scale, collect time-lapsed, bright-field images, segment highly variable and touching worms, and then store, visualize, and query dynamic phenotypes. To demonstrate the methodology, we treated somules with seven drugs that generated diverse responses and evaluated 45 static and kinetic response descriptors relative to concentration and time. For compound screening, we used the Mahalanobis distance to compare multidimensional phenotypic effects induced by 1323 approved drugs. Overall, we characterize both known anti-schistosomals and identify new bioactives. Apart from facilitating drug discovery, the multidimensional quantification provided by this platform will allow mapping of chemistry to phenotype.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Schistosoma
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Esquistosomicidas
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Esquistosomiasis mansoni
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Evaluación Preclínica de Medicamentos
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Descubrimiento de Drogas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Idioma:
En
Revista:
Commun Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos