ISO TS 04425-2023.docx

TECHNICA1.SPECIFICATIONISO/TS4425editionFirst2O23-O4Genomicsinformatics-Datae1.ementsandtheirmetadatafordescribingthemicrosate1.1.iteinstabi1.ity(MSI)informationofc1.inica1.massivepara1.1.e1.DNAsequencingInfbrmatiquegnomique-6怙mentsdedonnesetIeursmtadonnespourdicrireIesinformationsre1.ativesinstabi1.itdesmicrosate1.1.ites(MSI)dus6quenagemassifpara1.1.i1.ed,ADN1.SOTSRj5c2oOT©ISO2023COPYRIGHTPROTECTEDDOCUMENT©ISO2023IUirhM*hedbdi1.iUedotherwiseupdhi.orbmtndH0tf1.t×t'oni(nc4nmpe*Mqnrt<ifp5tcopyp>iat<)nmaytheinternetoranintranet,withoutpriorwrittenpermission.PermissioncanberequestedfromeitherISOattheaddressbe1.oworISO'smemberbodyinthecountryoftherequester.f),WV>fifiHipB1.andonnet8CH-1214Vernier,GenevaPhone：M1.22749O1.11觥ftte:丽丽BQrgPub1.ishedinSwitzer1.andContentsForeword1234567.2.2Genera1.B7.32Genera1.'7.3.5Subjectofcare97.5Performing107.5.3InformationOn1.ega1.1.yconfirmed107.7 7.6.2statusresu1.tinformation117.8 Recommended11838.3.1infOnnat1.On.13iiiPageIntroductionviScope1Normativereferences1Termsanddefinitions1Abbreviatedterms5Microsate1.1.iteinstabi1.ity(MSI)5Compositionofe1.ementsfordescribingMSIstatusonc1.inica1.DNANGSreport661Gener3166.2Summarypart7Fie1.dsandtheirnomenc1.atureofrequireddata77.1Genera1.77.2C1.iniedISeqUenCingOrder87.2.1C1.inica1.sequencingordercode7.2.3Dateandtime87.3Infornistiononsubjectofc6.97.3.1Subjectofcareidentifier7<<kn0rCfrer!，。97.3.4Subjectofcarebirthdate97.3.67.3.7Referringdiagnosis,107.4Informationon1.ega1.1.yauthorizedpersonorderingc1.inica1.sequencing107.4.1 Genera1.1.aboratory7.4.2 Genera1.107.4.3 Basicinformationonperforming1.aboratory107.5.4 ofreportgeneratorpersononsequencingreport7.6Biospccimeninformation107.6.1 Genera1.10MSITypeofspecimen,7.1,7.2,8.1,8.2,8.377777Genera1.11MSIstatus11Genera1.treatmentModicstioii.11C1.inica1.tria1.information11Fie1.dsandtheirnomenc1.atureofoptiona1.data128.1 Gener2.一.128.2 Referencegenomeinformation12MSIGenera1.8.3.2 CriteriaofMS1.status138.3.3 GenomicpositionfordeterminingMSIstatus138.3.5G1.inuf1.iiaaSiimti<4fi1.smrhEaitCrna1.iVemCthOd.一.138.4Sequencinginformation13841CIIniCa1.sequencingdate13胱41.Jcingc(J¾RWetrics138.4.4 Sequencingp1.atforminformation148.4.5 Ana1.ysisp1.atforminormatn14AnnexA(informative)Examp1.estructureofMSIstatusreport16Bib1.iography19ForewordISO(theInternationa1.OrganizationforStandardization)isawor1.dwidefederationofnationa1.standardsBuchugh(ISOtnrhniroibirH)tR¼,kWpaphngbody1.ntnoi6tat(bW(no!hntart>edmitteehasbeenestab1.ishedhastherighttoberepresentedonthatcommittee.Internationa1.organizations,governmenta1.andnongovernmenta1.,in1.iaisonwithISO,a1.sotakepartinthework.ISOco1.1.aboratesc1.ose1.ywiththee1.ectrotechnica1.standardization.Internationa1.E1.ectrotechnica1.Commission(IEC)ona1.1.mattersofTheproceduresusedtodeve1.opthisdocumentandthoseintendedforitsfurthermaintenanceareg殿F睽CiMteoSOIEC½teM槌必得杷油醐解蝴蟠($临酢%COrdanCe朗Fhtheeditoria1.ru1.esoftheSOIECDirectives,Part2(seewww.iso.org/directivcs).AnytradeusedinthisR曲拈OnHggd醐曲Bn捣媲蝴掘网群ns1.雅翩瞰R的阳赧府docf1.旅邮帖由银版subjectofanypatentrightsidentifiedduringthedeve1.oPmentCfxh。UXuJnMuUU4。beintheIntroductionand/orontheISO1.istofpatentdec1.arationsreceived(secwww.iso.org/patents).constitutenameendorsement,domentisinformationgivenfortheconvenienceofusersanddoesnotForanexp1.anationofthevo1.untarynatureofstandards,themeaningofISOspecifictermsand觊版U隅现dwn察脚阳6assE盛ftinwe憎s<曲船CnBar池恻Jdead唧乩e盘www.iso.org/iso/foreword.htm1.用i卜称锁/用用P沃edbyTechnica1.CommitteeISO/TC2151.Hea1.thinformatics,SubcommitteeAnyfeedbackorquestionsonthisdocumentshou1.dbedirectedtotheuser*snationa1.standardsbody.Acomp1.ete1.istingofthesebodiescanbefoundIntroductionMassive1.ypara1.1.e1.sequencingisahigh-throughputana1.ytica1.approachtonuc1.eicacidsequencingthathU。VVbWhO1.eUSedgAnhn1.的JmCaAftDimUMKfcBiddiniCific口iagtod女a空tw8ppJiMhtahMid(p<H9a1.izedHiedicineandprecisionmedicine.1SOTS20428(ihasbeendeve1.opedforc1.inica1.usage.1.rafio1.anti-cancerche11i1.>ffiePaies.varicnisreS?entStrategiestheconf11)iperforme1.111.ferf1.yy1.te11ronthatmaintainstheactiontoextractcancerce1.1.s.Recentoutcomesofc1.inica1.tria1.sshowthatthisimmunetherapyisefficientforsomepatientswhohaveaspecificmo1.ecu1.archaracteroftheirtumor三ss.ua,sbWersC4sc1.1H即刑郃曲随她理腼公办“8松1<era1.M1.BI½ersreportedthatthestatusofMSI(microsate1.1.iteinstabi1.ity)isregardedasJrbiomarkerthatdrugsbasedonimmuno-therapyaremoreefficientforthepatientwithMS1.-H(high)3.Bb件的照)璘格皿ftMiWI11AHPH8HgyAU创dmgn啦蜃自JQW&隘。H蛇单曲雀海帆g(ctswereapprovedforcompaniondiagnostics.Amongtheseproducts,threeNGSsequencingprovideMS!statsandva1.ueontheirNGSsequencingreport.C1.IA-certified1.absorequiva1.ent1.eve1.agenciesin.Itisforecastedthatmorec1.inica1.NGS£8册屈路g卦WHPfj1.是?而轧poAtusfromtheirmethods(qHoweverrthereisnostandardfordescribingMS!status,va1.ue,andmetadata.ISO/TS20428focusesMP5tusDHM帆梯sto&娜*Sdu三thedi懈h注锌A酬强曲8.皆忌3届.鹿跟耨曲片四a恨?itdifficu1.tforc1.iniciansandresearchersnoton1.ytouseMS1.statusresu1.tsforc1.inica1.decisionsbuta1.soforsecondaryana1.yzingpurposeswhenreceivingfrommorethanonesequencing1.ab.Re1.atedmetadatashou1.dbeessentia1.toexpandtheusageofMSIstatusresu1.ts.Inthisdocument,thedatae1.ementsandtheirstandardizedmetadataforMSIstatusine1.ectronichea1.threcordswi1.1.bedescribed.Thec1.inica1.reportforMSIwi1.1.providehe1.pfu1.infonnationonbioinformaticsana1.ysistohe1.pc1.inica1.decisions.GenomicsinformaticsDatae1.ementsandtheirmetadatafordescribingtheInicrosate1.1.iteinstabi1.ity(MSI)informationofc1.inica1.massivepara1.1.e1.DNAsequencing1ScopeThisdocumentidenti11esdatae1.ementsandmetadatatorepresenttheinformationaboutmicrosate1.1.iteinstabi1.ity(MSI)forreportingtheva1.ueofthebiomarkerusingc1.inica1.massivepara1.1.e1.DNAsequencing.ThisdocumentcoversinformationabouttheMSItestresu1.tandre1.ateddata,SUChasusedresources,datagenerationcondition,anddataprocessinginformationwhicharehe1.pfu1.toc1.inica1.diagnosisandresearch.Thisdocumentisnotintendedfor一(MSI),definingexperimenta1.protoco1.sormethodsforca1.cu1.atingtheva1.ueofmicrosate1.1.iteinstabi1.ityfortheotherbio1.ogica1.speciesthanhumanresource,orNNSftitWriW陆但熠WjWfinethods.曲南哨网幌丽电郦屈ent.对蛹限11nref*稣配枇WIa飒eediQ6na1.1.a&邮PIieS.aftentundatedreferences,the1.atesteditionofthereferenceddocument(inc1.udinganyamendments)app1.ies.ISO8601(a1.1.parts).DateandtimeRepresentationsforinformationinterchangeISO/TS22220:201fHea1.thinformaticsIdentificationofsubjectsofhea1.thcare0TSTe¾UWfMionsi确1111t5ProvideridentificationForthepurposesofthisdocument,thefo1.1.owingtermsanddefinitionsapp1.y.ISOandIECmaintaintermino1.ogydatabasesforuseinstandardizationatthefo1.1.owingaddresses:-ISOOn1.inebrowsingp1.atform:avai1abhat-hHps÷"www.MGF*obpbio1.ogica1.specimenbiospecimenspecimensamp1.eoftissue,bodyf1.uid,fc1.,orothersubstancethatisco1.1.ectedoracquiredtosupporttheassessmentdiagnosis,treatmentmitigationorpreventionofadisease,disorderorabnorma1.physica1.state,oritssymptoms(SOURCE:ISO/TS20428:2017,3.343.2c1.inica1.sequencingnextgenerationsequencingor1.atersequencingtechno1.ogieswithhumansamp1.esforc1.inica1.practiceandc1.inica1.tria1.sFguRCEISO/TS20428:2017,3.5de1.etioncontiguousremova1.ofoneormorebasesfromagenomicsequencefQURCE:ISO1EC23092-2:2020,3.4deoxyribonuc1.eicacidDNAmo1.e1.ethatencodesgeneticinformationinthenuc1.eusofce1.1.sy>gURCE:ISO25720:2009,4.7DNAsequencingdeterminingtheorderofnuc1.eotidebases(adenine,guanine,cytosineandthymine)inamo1.ecu1.eofDNNote1toentry:Sequenceisgenera1.1.ydescribedfromthe5,end.更gURCE:ISO17822:2020.3.19exonepartofthegenomeformedbyexons£9URCE:ISO/TS20428:2017.3.13genebasicunitOfheredi1.arymateria1.thatencodesandcontro1.stheexpressionofaproteinorprotein热Unitinde1.insertion(3.9)or/andde1.etion(3.3)EQURCE:ISO/TS20428:2017,3.18insertioncontiguousadditionofoneormorebasesintoagenomicsequence史?yRCE:ISO/IEC23092-2:2020,3.18microsate1.1.iterepetitiveDNAe1.ements,a1.soknownassimp1.esequencerepeats(SSR),consistingofshortin1.andemrepeatmotifsofonetoafewnuc1.eotidesthattendtooccurinnon-codingDNofeukaryoticgenomesandthataresometimesreferredtoasvariab1.enumberoftandemrepeats(VNTRs)3.11microsate1.1.iteinstabi1.ityMSig做IatChrepair(MMR)conditionOfgenetichypermutabi1.ity(predispositiontomutation)thatresu1.tsfromimpairedDNADNAmismatchrepairMMRsystemforFecognizingandrepairingerroneousinsertion,de1.etion,andmisincorporationofbasesthat用fjiseduringDNArep1.icationandrecombination,aswe1.1.asrepairingsomeformsofDNAdamagenuc1.eotidemonomerofanuc1.eicacidpo1.ymersuchasDNAorRNANbtehb吨SitiysNucKmD1.iA岫MIgkk1.nSnIjetterSw1.iMSOaIiPmInWs'。RNA).4h1.仅灿emi11Muhne;'Taj¢ertfijrmineDNAorRNAmo1.ecu1.eisgivenbythesequenceofitsnuc1.eotides,whichcanberepresentedasastringoverthea1.phabet("A?CVG,.T)inthecaseofDNA.andastringoverthea1.phabet('A,.tC.'G,U')inthecaseofRNA.Baseswithunknownmo1.ecu1.arcompositionaredenotedwith,N'.y>9RCE:ISO1EC23092-2:2020,3.20po1.ymerasechainreactionPCRinvitroenzymatictechniquetoincreasethenumberofcopiesofaspecificDNAfragmentbysevera1.ordersofmagnitudejSOURCE:ISO16577:2022,3.6.47qua1.ityscorePhredqua1.ityscoreQscoresequencingqua1.ityscoreofagivennuc1.eotidebaseHocetabirtg;eng.definedbythefo1.1.owingequation：Q三-101.og10(e),whereeistheestimatedprobabi1.ityoftheNote2tocntr),:Aqua1.ityScOreof20representsanerrorrateof1in100,withaCOrrcSpondingca1.1.accuracyof99%.Note3toentry：Higherqua1.ityscoresindicateasma1.1.erprobabi1.ity*oferror.1.owerqua1.ityscorescanresu1.tinasignificantportionofthereadsbeingunusab1.e.1.owqua1.ityscoresmaya1.soindicatefa1.se-positivevariantca1.1.s,resu1.tingininaccurateconc1.usions.更9gRCE:ISO20397-2:2021,3.30readtrpetypeofruninthesequencinginstrumentNote1toentry：Itcanbeeithersing1.e-endorpatred-end.Note2toentry：Sing1.e-end：Sing1.ereadrunsthesequencinginstrumentreadsfromoneendofafragmenttotheotherend.NotiiBaQfrmtrjhP*PdStOtdirtttiredendrunsreadfromoneendtotheotherandthenstartsanotherroundofSOURCE:ISO/TS20428:2017,3.27J3.17referencesequencenuc1.eicacidsequencewithbio1.ogica1.re1.evanceNmhint®校KyitEiKhRe9rddcHgbqHenCeSingIindted时出GandiniteanhiRiitH11hi<diUtE(巧zero.Thecoordinatesysteminthecontextofthisstandardiszero-based(Iejhefirstnuc1.eotidehascoordinate0,anditissaidtobeatposition0)and1.inear1.yincreaseswithinthestringfrom1.efttorightRCE:1SO1EC23092-1:2020,3.22readsequencereadfragmentednuc1.eotidesequencesthatareusedtoreconstructtheorigina1.sequencefornext-generationsequencingtechno1.ogies近四RCE:1SOTS20428:2017,3.26variationsequencevariationDNAsequencevariationdifferencesofDNAsequenceamongindividua1.sinapopu1.ationRCE:ISO25720:2009,4.8sma1.1.inde1.insertion(3.9)orde1.etion(3.3)of2nuc1.eotidesto100nuc1.eotides£2PRCE:1SOTS20428:2017,3.32subjectofcarepersonwhouses,orisapotentia1.userof,ahea1.thcareserviceyg1.RCE:1SOTS22220:2011,3.2,modifiedNotetoentryandsecondpreferredtermde1.eted.targetcapturemethodtocapturegenomicregionsofinterestfromaDNAsamp1.epriortosequencinggpyRCE:ISO/TS20428:2017,3.36targetedsequencingtechniqueusedforsequencingon1.ySeIeCted/targetedgenomicregionsofinterestfromaDNAsamp1.eF2yRCE:ISO/TS22692:2020,3.22,modifiedNotetoentryandsecondpreferredtermde1.eted.who1.eexonesequencingWES里当iqueforsequencingtheexomesoftheprotein-codinggenesinagenomewho1.egenomesequencingWGStechniquethatdeterminesthecomp1.eteDNsequenceofanorganism'sgenomeatasing1.etime(SOURCE:ISO/TS20428:2017,3.3944 AbbreviatedtermsCT1.A4CytotoxicT-1.ymphocyteAssociatedProtein4FHIRFastHea1.thcareInteroperabi1.ityResourcesIDMPIdentificationOfMedicinaIProductINNInternationa1.NonproprietaryNamesNCCNNationa1.ComprehensiveCancerNetWOrkNiHNationa1.InstitutesOfHea1.thPD-IProgrammedce1.1.deathprotein1WHOWor1.dHea1.thOrganization5 Microsate1.1.iteinstabi1.ity(MSI)andrepairmismatchesgcncs：dunngDNArep1.ication.PMS2.majorcomponentsfunctionenzymescodedCo1.orecta1.hereditarynon-po1.yposissyndromecancer(HNPCC)rIikeIythemostco1.orecta1.cancerhereditarydifferencesinrnutationorepigeneticinac1.ivationbothre1.atcdtonotaccumu1.ationsyndromesequencesrevea1.cdCancershigh1.yimmunogenictosignatre,inc1.udingoftumorneoantigenstmor-infi1.trating1.ymphocytes.foundstomach.sma1.1.intestine,pancreas,cancers,tractrandco1.orecta1.,Theendometia1.genomecontainscancersthanATCAnatomica1.TherapeuticChemica1.EBIEuropeanBioinformaticsInstituteH1.7Hea1.th1.eve1.SevenIMPIDInvestigationa1.MP1.DMP1.DMedicina1.ProductIdentiHerNGSNextGenerationSequencingPD-1.1.Programmeddeath-1.igand1SPRECStandardPREanaIyticaICodeUTNUniversa1.Tria1.NumberTheDNAmismatchrepair(MMR)pathwayp1.aysanimportantro1.einthece1.1.cyc1.eprocesstorecognizeforbythefo1.1.owingM1.H1.fMSH2rMSH6rTheandEPCAM.MMRarefourkeydoesn,tworkwhenmutationa1.inactivationinthefivegenesorepigeneticinactivationoccurs.Itisca1.1.edDeficiencyofmismatchrepair(dMMR).Oneofthemostre1.ateddiseasesis1.ynchsyndrome6.1.ynchsyndrome,a1.soknownascancer.Peop1.ewith1.ynchcoIorecta1.moreistogetcommoncauseofandothercancersatayoungerage(under50).Patientsdeve1.opdMMRtumorsfo1.1.owingtheinactivationofthesecondwi1.d-typea1.1.e1.ethroughsomaticmutation,1.ossofheterozygosity,orepigeneticsi1.encing.Thesea1.terations-thecaseofcancertype.However,istheon1.y1.ynchofshortbuta1.soofDNArepeatedthroughoutthegenome-specific1.ocationandanincreasedriskofma1.ignanttransformationincertaintissues.Thesetumorshaveahigherfrequencyofsomaticmutationscomparedwithnon-dMMRandandareassumedhave1.argerangeahighproportionof(highmutationburden)Defectivemismatchrepairresu1.tsinahightumormutationburdenandabundantneo-antigenformation,whichcanberecognizedbythehostimmunesystem.Microsate1.1.iteinstabi1.ity(MSI)isthein1.5%to3,5%ofa1.1.humanbi1.iarysuchasureter.humanovarian,andmoreof19mi1.1.ionmicrosate1.1.ites,shorttandemrepeatsofmotifsnf1nuc1.eotideto6nuc1.eotides,typica1.1.yspanning10nuc1.eotidesto60nuc1.eotidesintota1.1.ength7).However,iftheMMRfunctiondoesn,tworkwe1.1.,nuc1.eotideerroraccumu1.ates,especia1.1.yinthehumangenomicposition,inc1.udingmicrosate1.1.ites.8antb<!iuHedcefi三rQiiidunv(Qtion.microsate1.1.itescanserveasanindividua1.'smo1.ecu1.arbarcode,whichThestatusofMSIisusedasabiomarkerforpredictingtheprognosisOfco1.orecta1.cancerorse1.ecting网睡tsp脸ksbeRM丽确感mimmuneM螂瞄陷院½dec1.田园如胆S丽彩械W帼期Ioninhibitors.InMay2017,anewdrug-pembro1.izumab(KEYTRUDA®)wasapproved,whichisahumanizedantibodyagainsttheprogrammeddeathreceptor-1(PD-I)1forthetreatmentofpatients限阴醐眼唯触,a11Wi醐曲Iy陈h小城硼酬斛超岫岫既印AarbO的普醐触肿翩礴empwasure搞CIUd雁fi湖险IUm