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Title: A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery
Abstract Approximately 10% of the world’s population is at risk of schistosomiasis, a disease of poverty caused by theSchistosomaparasite. To facilitate drug discovery for this complex flatworm, we developed an automated high-content screen to quantify the multidimensional responses ofSchistosoma mansonipost-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.  more » « less
Award ID(s):
1817239 2401096
PAR ID:
10206628
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
Nature Publishing Group
Date Published:
Journal Name:
Communications Biology
Volume:
3
Issue:
1
ISSN:
2399-3642
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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