Abstract
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.
Highlights
Reference 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 conducted with a high level of confidence
We integrated a probabilistic network of H. microstoma interologs using a four-step scoring, filtering, integration and thresholding pipeline (Fig. 1a; Methods)
230 data sets from 16 species were included in the final integration step (Fig. 1b), resulting in a network of 3,474 proteins (∼ 30% of the H. microstoma somatic proteome) and 20,684 interactions: Hm_net (Fig. 3, upper)
Summary
Reference 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 conducted with a high level of confidence. The human bloodfluke Schistosoma mansoni and the tapeworms Echinococcus multilocularis and Hymenolepis microstoma are supported by near complete, chromosome-level assemblies [3,4,5], providing comprehensive and stable gene model estimates and syntenic relationships, as well as allowing the higher order architecture of their genomes to begin to be investigated. A draft genome was published in 2013 [4] and was followed in 2015 by the public release of an up-dated assembly (v.2) based on additional Illumina data, as described in [5] This assembly was used to investigate differentiallyexpressed genes among different life cycle stages and regions of the adult, strobilar worm [5], and for characterisation of the microRNA complement [7]. With the basic assembly and annotation of these inaugural helminth sequencing projects effectively complete, we can begin to undertake systems-level analyses in parasitic flatworms for the first time
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