Project description:Hymenolepis spp. (H. diminuta, H. nana and H. microstoma) are rodent-hosted tapeworms (Platyhelminthes: Cestoda) that have been used as laboratory and teaching models since the 1950s, and consequently much of our understanding of the basic physiology, biochemistry and anatomy of tapeworms in general stems from research using these species. As representatives of the order Cyclophyllidea, they are closely related to species with significant medical and economic importance such as Taenia and Echinococcus spp., but unlike these may be maintained in vivo using only laboratory mice and flour beetles (n.b. Echinoccous spp. are hosted by foxes and Taenia spp. are hosted by pigs or cows). This effort brings a classical laboratory model into the genomic age, allowing researchers in silico access to its genome and expressed gene transcripts and thereby greatly expediting research directed at understanding the genetic basis of tapeworm biology.
Project description:BackgroundReference genome and transcriptome assemblies of helminths have reached a level of completion whereby secondary analyses that rely on accurate gene estimation or syntenic relationships can be now conducted with a high level of confidence. Recent public release of the v.3 assembly of the mouse bile-duct tapeworm, Hymenolepis microstoma, provides chromosome-level characterisation of the genome and a stabilised set of protein coding gene models underpinned by bioinformatic and empirical data. However, interactome data have not been produced. Conserved protein-protein interactions in other organisms, termed interologs, can be used to transfer interactions between species, allowing systems-level analysis in non-model organisms.ResultsHere, we describe a probabilistic, integrated network of interologs for the H. microstoma proteome, based on conserved protein interactions found in eukaryote model species. Almost a third of the 10,139 gene models in the v.3 assembly could be assigned interaction data and assessment of the resulting network indicates that topologically-important proteins are related to essential cellular pathways, and that the network clusters into biologically meaningful components. Moreover, network parameters are similar to those of single-species interaction networks that we constructed in the same way for S. cerevisiae, C. elegans and H. sapiens, demonstrating that information-rich, system-level analyses can be conducted even on species separated by a large phylogenetic distance from the major model organisms from which most protein interaction evidence is based. Using the interolog network, we then focused on sub-networks of interactions assigned to discrete suites of genes of interest, including signalling components and transcription factors, germline multipotency genes, and genes differentially-expressed between larval and adult worms. Results show not only an expected bias toward highly-conserved proteins, such as components of intracellular signal transduction, but in some cases predicted interactions with transcription factors that aid in identifying their target genes.ConclusionsWith key helminth genomes now complete, systems-level analyses can provide an important predictive framework to guide basic and applied research on helminths and will become increasingly informative as new protein-protein interaction data accumulate.