The next generation of antiparasitics will likely be discovered through high-content and high-throughput screening using automated microscopy. As the amount of antiparasitic drug screening data swells at a rapid pace, researchers need to keep up by also developing analytical tools that can quickly and reliably analyze these data. A variety of proprietary and open-source software exists for these approaches, but none that are oriented towards images of worms (whether parasitic or free-living). We developed wrmXpress to fill this software gap.
wrmXpress has been used in screens to identify compounds with microfilaricidal and macrofilaricidal effects, characterize structure-activity relationships of drug classes against schistosomes, and assess the effects of cholinergic compounds on worm feeding. It has already been used to analyze dozens of terabytes worth of data.
The next generation of wrmXpress will include a graphical user interface for more widespread and inclusive use, include modules for new phenotypic endpoints, and incorporate deep learning into image analysis. Our collaboration with the Zamanian Lab seeks to push the field forward and provide a flexible, intuitive software that is used by diverse labs and companies around the world.
wrmXpress: A modular package for high-throughput image analysis of parasitic and free-living worms
Author summary Advances in automated microscopy have led to the proliferation of high-throughput experimental techniques to screen drugs for activity against parasitic worms, which infect billions of people around the world.
Multivariate chemogenomic screening prioritizes new macrofilaricidal leads - Communications Biology
Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential.
Phenotypic profiling of macrocyclic lactones on parasitic Schistosoma flatworms
Macrocyclic lactones are front-line therapies for parasitic roundworm infections, but there are no comprehensive studies on the activity of this drug class against parasitic flatworms. Ivermectin is well known to be inactive against flatworms. However, the structure-activity relationship of macrocyclic lactones may vary across phyla, and it is entirely possible other members of this drug class do in fact show antiparasitic activity on flatworms. For example, there are several reports hinting at the anti-schistosomal activity of doramectin and moxidectin.
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GitHub - zamanianlab/wrmXpress
This package contains a variety of Python and CellProfiler pipelines used for the analysis of worm imaging data. Some of these are specific to Zamanian lab experimental pipelines, but many of the modules should be robust to a diversity of species and experimental procedures.