Needles in the EST Haystack Large-Scale Identification and Analysis of Excretory-Secretory (ES) Proteins in Parasitic Nematodes Using Expressed Sequence Tags (ESTs) 英文参考文献.docVIP

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Needles in the EST Haystack Large-Scale Identification and Analysis of Excretory-Secretory (ES) Proteins in Parasitic Nematodes Using Expressed Sequence Tags (ESTs) 英文参考文献.doc

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Needles in the EST Haystack Large-Scale Identification and Analysis of Excretory-Secretory (ES) Proteins in Parasitic Nematodes Using Expressed Sequence Tags (ESTs) 英文参考文献

NeedlesintheESTHaystack:Large-ScaleIdentification andAnalysisofExcretory-Secretory(ES)Proteinsin ParasiticNematodesUsingExpressedSequenceTags (ESTs) ShivashankarH.Nagaraj1,RobinB.Gasser2,ShobaRanganathan1,3* 1DepartmentofChemistryandBiomolecularSciences,MacquarieUniversity,Sydney,NewSouthWales,Australia,2DepartmentofVeterinaryScience,TheUniversityof Melbourne,Werribee,Victoria,Australia,3DepartmentofBiochemistry,YongLooLinSchoolofMedicine,NationalUniversityofSingapore,Singapore Abstract Background:Parasiticnematodesofhumans,otheranimalsandplantscontinuetoimposeasignificantpublichealthand economic burden worldwide, due to the diseases they cause. Promising antiparasitic drug and vaccine candidates have beendiscoveredfromexcretedorsecreted(ES)proteinsreleasedfromtheparasiteandexposedtotheimmunesystemof thehost.Miningtheentireexpressedsequencetag(EST)dataavailablefromparasiticnematodesrepresentsanapproachto discoversuchEStargets. Methods and Findings: In this study, we predicted, using EST2Secretome, a novel, high-throughput, computational workflowsystem,4,710ESproteinsfrom452,134ESTsderivedfrom39differentspeciesofnematodes,parasiticinanimals (including humans) or plants. In total, 2,632, 786, and 1,292 ES proteins were predicted for animal-, human-, and plant- parasiticnematodes.Subsequently,wesystematicallyanalysedESproteinsusingcomputationalmethods.Ofthese4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently havingnosignificantmatchtoanymoleculeavailableinpublicdatabases.OftheC.eleganshomologues,267hadstrong ‘‘loss-of-function’’ phenotypes by RNA interference (RNAi) in this nematode. We could functionally classify 1,948 (41.3%) sequences using the Gene Ontology (GO) terms, establish pathway associations for 573 (12.2%) sequences using Kyoto EncyclopaediaofGenesandGenomes(KEGG),andidentifyproteininteractionpartnersfor1,774(37.6%)molecules.Wealso mapped758(16.1%)proteinstoproteindomainsincludingt