IGroundbreaking TB kunye neDR-TB Diagnostic Solution ngu #Macro & Micro -Test!

Isixhobo esitsha sokuFunyaniswa kweSifo sePhepha kunye nokuFunyaniswa koKuchasana kweziyobisi: Isizukulwana esitsha sokuSetyenziswa kokuJoliswe (tNGS) kudityaniswe neSifundo soShishino seSifo sePhepha ngoVavanyo lwe-hypersensitivity

Ingxelo yoncwadi: I-CCa: imodeli yokuxilonga esekelwe kwi-tNGS kunye nokufunda komatshini, ofanelekileyo kubantu abanesifo sofuba esincinci kunye ne-meningitis ye-tuberculous.

Isihloko se-Thesis: Ulandelelwano lwesizukulwana esilandelayo esijoliswe kwiTuberculous kunye nokufunda koomatshini: isicwangciso sokuxilongwa kwe-ultra-sensitive ye-paucific pulmonary tubulars kunye ne-meningitis ye-tubular.

Ngamaxesha athile: 《Clinica Chimica Acta》

UKUBA: 6.5

Umhla wokupapashwa: Janyuwari 2024

Idityaniswe neYunivesithi yaseTshayina yeSayensi yeSayensi kunye neSibhedlele saseBeijing Chest yeYunivesithi yezoNyango, iMacro kunye neMicro-Test yaseka imodeli yokuxilongwa kwesifo sephepha esekwe kwisizukulwana esitsha sobuchwephesha obujoliswe ekulandeleleni (tNGS) kunye nendlela yokufunda koomatshini, ebonelela nge-ultra-high. ukufumanisa ubuntununtunu besifo sephepha esineebhaktheriya ezimbalwa kunye ne-meningitis ye-tuberculous, inike indlela entsha yokuxilongwa kwe-hypersensitivity yokuxilongwa kwekliniki yeentlobo ezimbini zesifo sephepha, kwaye yanceda ukuxilongwa ngokuchanekileyo, ukufumanisa ukuxhathisa kumachiza kunye nonyango lwesifo sephepha.Kwangaxeshanye, kufunyaniswe ukuba iplasma cfDNA yesigulana ingasetyenziswa njengohlobo olufanelekileyo lwesampulu yesampulu yeklinikhi kuxilongo lwe-TBM.

Kolu phononongo, iisampulu zeplasma ezingama-227 kunye neesampulu zolwelo lwe-cerebrospinal zisetyenziselwe ukuseka amaqela amabini ekliniki, apho iisampulu zoxilongo lwelabhoratri zasetyenziselwa ukuseka imodeli yokufunda ngomatshini wokuxilongwa kwesifo sephepha, kunye neesampulu zoxilongo lweklinikhi ziye zasetyenziselwa ukuqinisekisa imodeli yokuxilonga.Zonke iisampulu zaqale zajoliswa yiphuli eyilwe ngokukodwa ekujoliswe kuyo ukubamba i-Mycobacterium tuberculosis.Emva koko, ngokusekelwe kwidatha yokulandelelana kwe-TB-tNGS, imodeli yomthi wesigqibo isetyenziselwa ukwenza i-5-fold cross-validation kwi-training and validation seti ye-laboratory diagnostic queue, kunye nemigangatho yokuxilongwa kweesampuli ze-plasma kunye neesampuli ze-cerebrospinal fluid zifunyenwe.Umda ofunyenweyo ungeniswa kwiiseti ezimbini zovavanyo lokuxilongwa kweklinikhi ukuze kubonwe, kwaye ukusebenza kokuxilonga komfundi kuvavanywa yi-ROC curve.Ekugqibeleni, imodeli yokuxilongwa kwesifo sofuba yafunyanwa.

Isazobe soku-1 soyilo loyilo lophando

Iziphumo: Ngokwemilinganiselo ethile ye-CSF yesampuli ye-DNA (AUC = 0.974) kunye nesampuli ye-plasma cfDNA (AUC = 0.908) egqitywe kolu cwaningo, phakathi kweesampuli ze-227, uvakalelo lwesampulu ye-CSF yi-97.01%, i-specific i-95.65%, kwaye uvakalelo kunye neenkcukacha zesampulu yeplasma yayiyi-82.61% kunye ne-86.36%.Kuhlalutyo lweesampulu ezidityanisiweyo ezingama-44 zeplasma cfDNA kunye ne-cerebrospinal fluid DNA evela kwizigulane ze-TBM, isicwangciso sokuxilonga solu phononongo sinokuhambelana okuphezulu kwe-90.91% (40/44) kwiplasma cfDNA kunye ne-cerebrospinal fluid DNA, kwaye ubuntununtunu yi-95.45% (42/44).Kubantwana abanesifo sephepha semiphunga, isicwangciso sokuxilonga solu phononongo sinovakalelo ngakumbi kwiisampuli zeplasma kuneziphumo zokufumanisa i-Xpert yeesampulu zejusi yesisu kwizigulane ezifanayo (28.57% VS 15.38%).

Umzobo 2 Uhlalutyo lwentsebenzo yemodeli yokuxilongwa kwesifo sephepha kwiisampulu zabemi

Umzobo 3 Iziphumo zoxilongo lweesampulu ezidityanisiweyo

Isiphelo: Indlela yokuxilonga i-hypersensitive ye-tuberculosis yasungulwa kolu cwaningo, olunokubonelela ngesixhobo sokuxilonga ngeyona nto iphezulu yokufumanisa izigulane zeklinikhi ezine-oligobacillary tuberculosis (inkcubeko embi).Ukufunyanwa kwesifo sephepha esine-hypersensitive esekwe kwiplasma cfDNA inokuba luhlobo olufanelekileyo lwesampulu yokuxilongwa kwesifo sephepha esisebenzayo kunye ne-meningitis yesifuba (iisampulu zeplasma kulula ukuziqokelela kunolwelo lwe-cerebrospinal kwizigulana ekurhanelwa ukuba zinesifo sephepha sobuchopho).

Ikhonkco lokuqala: https://www.sciencedirect.com/science/article/pii/s0009898123004990?nge%3Dihub

Intshayelelo emfutshane yovavanyo lweemveliso zesifo sephepha seMacro kunye neMicro-Test

Kwimeko yesampulu entsonkothileyo yezigulane zesifo sephepha kunye neemfuno ezahlukeneyo, iMacro & Micro-Test ibonelela ngeseti epheleleyo yezisombululo ze-NGS zokutsalwa kotywala kwiisampulu zesikhohlela, ukwakhiwa kwethala leencwadi leQualcomm kunye nolandelelwano, kunye nohlalutyo lwedatha.Iimveliso zigubungela ukuxilongwa ngokukhawuleza kwezigulana zesifo sephepha, ukuchongwa kweyeza lokunganyangeki kwesifo sephepha, ukuchwetheza kwesifo sephepha se-mycobacterium kunye ne-NTM, ukuxilongwa kwe-hypersensitivity ye-bacteria-negative tuberculosis kunye nabantu abanesifo sephepha, njl.

Izixhobo zokufumanisa uthotho lwesifo sephepha kunye ne-mycobacteria:

Inombolo yomba Igama lemveliso umxholo wovavanyo lwemveliso isampuli uhlobo imodeli esebenzayo
HWTS-3012 I-arhente yokukhulula isampuli Isetyenziswe kunyango lokunyibilika kweesampuli zesikhohlela, ifumene inombolo yerekhodi yodidi lokuqala, iSutong Machinery Equipment 20230047. isikhohlela
HWTS-NGS-P00021 Ikhithi yokufumanisa ubungakanani be-Qualcomm ye-hypersensitive tuberculosis (indlela yokubamba iprobe) I-non-invasive (i-biopsy yolwelo) ukufumanisa i-hypersensitivity ye-bacteria-negative pulmonary tuberculosis kunye ne-brain nodules;Iisampulu zabantu ekurhaneleka ukuba bosulelwe sisifo sephepha okanye i-mycobacteria engeyiyo-isifo sephepha zahlalutywa ngolandelelwano olunzulu lwe-metagenomics, kunye nolwazi lokufumanisa ukuba ingaba isifo sephepha okanye esingesosifo sephepha i-mycobacteria yasosulelekile kwaye eyona nkcazelo iphambili yokuxhathisa amachiza ye-mycobacterium tuberculosis. zabonelelwa. Igazi le-peripheral, i-alveolar lavage fluid, i-hydrothorax kunye ne-ascites, isampuli yokujolisa, i-cerebrospinal fluid. Isizukulwana sesibini
HWTS-NGS-T001 Ukuchwetheza kwe-Mycobacterium kunye nekiti yokufumanisa ukuxhathisa kumachiza (indlela yolandelelwano yokwandisa ubuninzi be-multiplex) Uvavanyo lokuchwetheza lwe-Mycobacterium, kuquka i-MTBC kunye ne-187 NTM;Ukufunyaniswa kokunganyangeki ngamachiza kwesifo sephepha iMycobacterium kugubungela amachiza ali-13 kunye neendawo ezili-16 ezingundoqo zotshintsho lwemfuza yokuxhathisa kumachiza. Isikhohlela, i-alveolar lavage fluid, i-hydrothorax kunye ne-ascites, isampulu yokugqalwa kokugqobhoza, ulwelo lwe-cerebrospinal. Iqonga lesibini/lesithathu lesibini

Amanqaku aphambili: HWTS-NGS-T001 Ukuchwetheza kweMycobacterium kunye nekhithi yokubona ukuxhathisa kumachiza (indlela yokwandisa i-multiplex)

Intshayelelo yemveliso

Imveliso isekelwe kumayeza angundoqo omgca wokuqala nowesibini ochazwe kwizikhokelo zonyango lwe-TB ye-WHO, i-macrolides kunye ne-aminoglycosides edla ngokusetyenziswa kwizikhokelo zonyango ze-NTM, kunye neendawo zokunganyangeki ngamachiza zigubungela lonke iqela elinye leendawo ezinxulumene nokunganyangeki ngamachiza kwi-TB. Ikhathalogu ye-WHO Mycobacterium tuberculosis complex mutation catalogue, kunye nezinye ezixeliweyo zoxhathiso kumachiza kunye neziza zotshintsho ngokophando kunye neenkcukacha-manani zoncwadi olunamanqaku aphezulu ekhaya naphesheya.

Ukuchongwa kokuchwetheza kusekelwe kwiintlobo ze-NTM ezishwankathelweyo kwimigaqo ye-NTM epapashwe yi-Chinese Journal yeSifo sePhepha kunye neZifo zokuphefumla kunye nokuvumelana kweengcali.Iiprimer zokuchwetheza eziyilelweyo zinokukhulisa, zilandelelane kwaye zichaze ngaphezu kwe-190 yeentlobo ze-NTM.

Ngeteknoloji yokukhulisa i-multiplex ye-PCR ejoliswe kuyo, imfuza ye-genotyping kunye nemfuza enganyangekiyo ngamachiza ye-Mycobacterium ziye zandiswa yi-multiplex PCR, kunye nendibaniselwano ye-amplicon yofuzo ekujoliswe kuyo ukuba kufunyaniswe.Iimveliso ezikhulisiwe zingakhiwa kwisizukulwana sesibini okanye kwisizukulwana sesithathu kwiilayibrari ezilandelelanayo eziphezulu, kwaye zonke iiplatifomu zokulandelelana zesizukulwana sesibini kunye nesithathu zingaba phantsi kokulandelelaniswa okunzulu ukufumana ulwazi lokulandelelana kweejene ezijoliswe kuzo.Ngokuthelekisa notshintsho olwaziwayo oluqulethwe kwisiseko sedatha esakhelwe ngaphakathi (kubandakanya ikhathalogu ye-WHO Mycobacterium tuberculosis complex mutation catalogue kunye nobudlelwane bayo noxhathiso lwamachiza), utshintsho olunxulumene nokuxhathisa kumachiza okanye ukuba sengozini kwamachiza achasene nesifo sephepha kwamiselwa.Idityaniswe nesisombululo sonyango lwesampulu yesikhohlela esizivulayo seMacro & Micro-Test, ingxaki yomgangatho ophantsi we-nucleic acid amplification yeesampulu zesikhohlela saseklinikhi (ubuphinda-phindwe kashumi obuphezulu kunobo beendlela zesintu) yasonjululwa, ukuze ukubhaqwa kolandelelwano lokunganyangeki ngamachiza kunokwazi isetyenziswe ngokuthe ngqo kwiisampuli zesikhohlela sekliniki.

Uluhlu lokufumanisa imveliso

34iijini ezinxulumene-nokumelana neziyobisi ze18amachiza okulwa nesifo sephepha kunye6Amachiza e-NTM afunyenwe, egqumayo297iindawo zokunganyangeki ngamachiza;Iintlobo ezilishumi zesifo sephepha seMycobacterium nangaphezulu190iintlobo ze-NTM zichongiwe.

Itheyibhile 1: Ulwazi lwe-18 + 6 Iziyobisi +190 + NTM

Inzuzo yemveliso

Ukuziqhelanisa okuqinileyo nekliniki: iisampulu zesikhohlela zinokubhaqwa ngokuthe ngqo nge-arhente yokuzinyibilikisa ngaphandle kwenkcubeko.

Umsebenzi wokulinga ulula: umjikelo wokuqala wokwandisa umsebenzi ulula, kwaye ukwakhiwa kwethala leencwadi kugqitywa kwiiyure ze-3, eziphucula ukusebenza kakuhle.

Ukuchwetheza okuBanzi kunye noxhathiso lwamachiza: ukugubungela iindawo zokuchwetheza kunye nokuxhathisa amachiza e-MTB kunye ne-NTM, ezingamanqaku aphambili enkxalabo yeklinikhi, ukuchwetheza ngokuchanekileyo kunye nobhaqo wokuxhathisa amachiza, ukuxhasa isoftware yohlalutyo oluzimeleyo, kunye nokuvelisa iingxelo zohlalutyo ngokucofa kanye.

Ukuhambelana: ukuhambelana kwemveliso, ukulungelelanisa kwi-ILM kunye ne-MGI / ONT iqonga.

Ukuchazwa kwemveliso

Ikhowudi yemveliso Igama lemveliso Iqonga lokufumanisa iinkcukacha
HWTS-NGS-T001 Ukuchwetheza kweMycobacterium kunye nekiti yokubona ukuxhathisa kumachiza (indlela yokukhulisa i-multiplex) ONT, Illumina, MGI, Salus pro 16/96rxn

Ixesha lokuposa: Jan-23-2024