Abstract
BackgroundNeglected diseases caused by helminth infections impose a massive hindrance to progress in the developing world. While basic research on parasitic flatworms (platyhelminths) continues to expand, researchers have yet to broadly adopt a free-living model to complement the study of these important parasites.MethodsWe report the high-coverage sequencing (RNA-Seq) and assembly of the transcriptome of the planarian Girardia tigrina across a set of dynamic conditions. The assembly was annotated and extensive orthology analysis was used to seed a pipeline for the rational prioritization and validation of putative anthelmintic targets. A small number of targets conserved between parasitic and free-living flatworms were comparatively interrogated.Results240 million paired-end reads were assembled de novo to produce a strictly filtered predicted proteome consisting of over 22,000 proteins. Gene Ontology annotations were extended to 16,467 proteins. 2,693 sequences were identified in orthology groups spanning flukes, tapeworms and planaria, with 441 highlighted as belonging to druggable protein families. Chemical inhibitors were used on three targets in pharmacological screens using both planaria and schistosomula, revealing distinct motility phenotypes that were shown to correlate with planarian RNAi phenotypes.ConclusionsThis work provides the first comprehensive and annotated sequence resource for the model planarian G. tigrina, alongside a prioritized list of candidate drug targets conserved among parasitic and free-living flatworms. As proof of principle, we show that a simple RNAi and pharmacology pipeline in the more convenient planarian model system can inform parasite biology and serve as an efficient screening tool for the identification of lucrative anthelmintic targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-014-0622-3) contains supplementary material, which is available to authorized users.
Highlights
Neglected diseases caused by helminth infections impose a massive hindrance to progress in the developing world
De novo transcriptome assembly To improve the odds of comprehensive transcript capture, RNA was isolated from G. tigrina across a set of dynamic conditions
Planaria were passaged through a feed-starve cycle under different conditions prior to RNA extraction (Figure 1A)
Summary
Neglected diseases caused by helminth infections impose a massive hindrance to progress in the developing world. Trematodes (flukes) and cestodes (tapeworms) are the etiological agents of several Neglected Tropical Diseases (NTDs) that disproportionately devastate the health and economic prospects of the poor across much of the developing world. Echinococcosis and cysticercosis, The prioritization of flatworm-associated NTDs by the World Health Organization [4] underscores the urgency of efforts to control infection and to develop new anthelmintic treatments. The threat of drug resistance [5] further calls attention to the need for novel pipelines for drug target validation and drug discovery [6]. Against this backdrop, free-living flatworms represent a new and potentially powerful screening model for parasite drug
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