Anti-schistosomal Intervention Targets Identified by Lifecycle Transcriptomic Analyses 英文参考文献.docVIP

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Anti-schistosomal Intervention Targets Identified by Lifecycle Transcriptomic Analyses 英文参考文献.doc

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Anti-schistosomal Intervention Targets Identified by Lifecycle Transcriptomic Analyses 英文参考文献

Anti-schistosomalInterventionTargetsIdentifiedby LifecycleTranscriptomicAnalyses JenniferM.Fitzpatrick1,EmilyPeak2,SamirahPerally2,IainW.Chalmers2,JohnBarrett2,TimothyP. Yoshino3,AlasdairC.Ivens4,KarlF.Hoffmann1,2* 1Department of Pathology, University of Cambridge, Cambridge, United Kingdom, 2Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University,Aberystwyth,UnitedKingdom,3DepartmentofPathobiologicalSciences,SchoolofVeterinaryMedicine,UniversityofWisconsin,Madison,Wisconsin,United StatesofAmerica,4FiosGenomics,ETTC,King’sBuildings,Edinburgh,UnitedKingdom Abstract Background: Novel methods toidentify anthelmintic drug andvaccine targets areurgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification of exploitable molecules essential for successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach,employingbothstatisticalandnetworkanalysesoftranscriptomicdata,foridentifyingnewimmunoprophylactic andtherapeuticleadtargetstocombatschistosomiasis. Methodology/PrincipalFindings:UtilisationofaSchistosomamansonioligonucleotideDNAmicroarrayconsistingof37,632 elements enabled gene expression profiling from 15 distinct parasite lifecycle stages, spanning three unique ecological niches.Statisticalapproachesofdataanalysisrevealeddifferentialexpressionof973geneproductsthatminimallydescribe the three major characteristics of schistosome development: asexual processes within intermediate snail hosts, sexual maturationwithindefinitivevertebratehostsandsexualdimorphismamongstadultmaleandfemaleworms.Furthermore, we identified a group of 338 constitutively expressed schistosome gene products (including 41 transcripts sharing no sequencesimilarityoutsidethePlatyhelminthes),whicharelikelytobeessentialforschistosomelifecycle