2020
DOI: 10.1038/s42003-020-01402-5
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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 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,… Show more

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Cited by 17 publications
(9 citation statements)
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“…However, to achieve detectable and reliable signals, these methods require 200–400 NTS per well and are limited to end-point analyses that do not provide any information on temporal evolution, which can be captured in impedance-based measurements ( Peak et al., 2010 ; Panic et al., 2015b ; Aguiar et al., 2017 ). Finally, automated image-acquisition systems have been proposed for enabling high-throughput and quantitative analysis of schistosomula phenotypes during drug exposure assays ( Lee et al., 2012 ; Chen et al., 2020 ). By tracking the temporal evolution of multiple phenotypic aspects, such as parasite morphology, size, and movements, these methods have the potential to produce high-dimensional data with additional information on drug action to support compound optimization, which is most likely missed by monitoring motility alone.…”
Section: Discussionmentioning
confidence: 99%
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“…However, to achieve detectable and reliable signals, these methods require 200–400 NTS per well and are limited to end-point analyses that do not provide any information on temporal evolution, which can be captured in impedance-based measurements ( Peak et al., 2010 ; Panic et al., 2015b ; Aguiar et al., 2017 ). Finally, automated image-acquisition systems have been proposed for enabling high-throughput and quantitative analysis of schistosomula phenotypes during drug exposure assays ( Lee et al., 2012 ; Chen et al., 2020 ). By tracking the temporal evolution of multiple phenotypic aspects, such as parasite morphology, size, and movements, these methods have the potential to produce high-dimensional data with additional information on drug action to support compound optimization, which is most likely missed by monitoring motility alone.…”
Section: Discussionmentioning
confidence: 99%
“…By tracking the temporal evolution of multiple phenotypic aspects, such as parasite morphology, size, and movements, these methods have the potential to produce high-dimensional data with additional information on drug action to support compound optimization, which is most likely missed by monitoring motility alone. For example, a system compatible with high-throughput image acquisition and automated plate handling (SchistoView) was used to evaluate schistosomula at a few discrete time points in a 96-well-plate format and yielded more than 15 parameters for describing parasite phenotypes ( Chen et al., 2020 ). However, SchistoView requires large volume data storage (∼15 MB per unit per time point as opposed to ∼0.8 MB per unit per time point for impedance) and significant computational resources for analyzing complex phenotypic data.…”
Section: Discussionmentioning
confidence: 99%
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“…Different approaches to evaluate compounds against juvenile or mature worms have been developed 12 . Innovative assays have been devised for the analysis of schistosomula using image based [13][14] , metabolic [15][16] and electro-impedance techniques 17 . Importantly, several of them can be automated and are able to assay a large number of juvenile worms, generating more relevant data, although they give no information about the efficacy of the compounds on the adult stage.…”
Section: Introductionmentioning
confidence: 99%
“…The most advanced assays have been devised for the analysis of schistosomula. These assays use and sometimes combine image-based analysis allowing high-content screening [14,15], metabolic [16,17] and electro-impedance techniques [18,19]. Importantly, several of them can be automated and are able to assay a large number of juvenile worms for high-throughput screening (HTS), generating more relevant data, although they give no information about the efficacy of the compounds on the adult stage.…”
Section: Introductionmentioning
confidence: 99%