SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis 英文参考文献.docVIP

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SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis 英文参考文献.doc

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SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis 英文参考文献

o Openaccess,freelyavailableonline PL S MEDICINE SARSTransmissionPatterninSingapore ReassessedbyViralSequenceVariation Analysis Jianjun Liu1*,Siew Lan Lim1,Yijun Ruan1,AiEe Ling2,Lisa F.P.Ng1,Christian Drosten3,Edison T.Liu1, Lawrence W. Stanton1,Martin L.Hibberd1 1 Genome Institute of Singapore, Singapore, Singapore, 2 Department of Pathology, Singapore General Hospital, Singapore, 3 Bernhard Nocht Institute for Tropical Medicine,NationalReferenceCenterforTropicalInfectiousDiseases,Hamburg,Germany ABSTRACT CompetingInterests:The authors have declared that no competing interests exist. ETL is a member of the Editorial Board of PLOS Medicine. Background Epidemiological investigations of infectious disease are mainly dependent on indirect contactinformationandonlyoccasionallyassistedbycharacterizationofpathogensequence AuthorContributions:JL,ETL, LWS,andMLHdesignedthestudy. JL,SLL,andCDanalyzedthedata. LFPNperformedtheexperiments. YRcoordinatedsampleacquiring andprovidedthegenomesequence variationdatafordesigningMS assays.AELprovidedSARS-CoV samplesfrompatients.JL,SLL,YR, AEL,LFPN,CD,ETL,LWS,and MLHcontributedtowritingthe paper. variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive.Wepresenthereanovelapplicationofmassspectrometry(MS)–basedtechnology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectivelytothesevereacuterespiratorysyndrome(SARS)outbreakinSingapore. MethodsandFindings The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequencevariationswasdeterminedtobe95%with75copiesofviralRNAperreaction,which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolatesfromthedifferentstagesoftheSingaporeoutbreakidentifiedninesequencevariations thatcoulddefinethemolecularrelationshipbetweenthemandpoin