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 seYunivesithi yezoNyango, iMacro kunye neMicro-Test yaseka imodeli yokuxilongwa kwesifo sephepha esekwe kwisizukulwana esitsha solandelelwano olujoliswe kuyo (tNGS) itekhnoloji kunye nendlela yokufunda yomatshini, eyabonelela ngobuntununtunu besifo sephepha kunye neebhaktheriya ezimbalwa kunye ne-meningitis ye-tuberculous, yabonelela ngoxilongo olutsha lwe-hyperculosis yokuxilongwa kwesifo sephepha kunye nokuxilongwa okuchanekileyo kwesifo sephepha, ukuxilongwa kwe-hyperculosis echanekileyo yokuxilongwa kwesifo sephepha kunye nokuxilongwa kwesifo sephepha. ukufumanisa kunye nokunyangwa kwesifo sephepha. Kwangaxeshanye, kufumaniseka ukuba iplasma cfDNA yesigulana ingasetyenziswa njengohlobo olufanelekileyo lwesampulu yesampulu yeklinikhi kuxilongo lwe-TBM.

Kolu phononongo, iisampulu ze-plasma ezingama-227 kunye neesampulu ze-cerebrospinal fluid zasetyenziselwa ukuseka amaqela amabini ekliniki, apho iisampulu zoxilongo lwebhubhoratri zasetyenziselwa ukuseka imodeli yokufunda ngomatshini wokuxilongwa kwesifo sephepha, kwaye iisampulu zoxilongo lweklinikhi zasetyenziselwa ukuqinisekisa imodeli yoxilongo olusekiweyo. 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-speciality yi-95.65%, kunye ne-plasma ye-8 kunye ne-speciation ye-861% 86.36%. Kuhlalutyo lweesampulu ezidityanisiweyo ze-44 ze-plasma cfDNA kunye ne-cerebrospinal fluid DNA evela kwizigulane ze-TBM, isicwangciso sokuxilonga solu phononongo sinokuhambelana okuphezulu kwe-90.91% (40/44) kwi-plasma cfDNA kunye ne-cerebrospinal fluid DNA, kunye novakalelo 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:

Inqaku lenqaku	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 non-tuberculosis mycobacteria zahlalutywa ngolandelelwano olunzulu lwe-metagenomics, kunye nolwazi lokufumanisa ukuba ingaba isifo sephepha okanye i-non-tuberculosis mycobacteria yosulelekile kwaye ulwazi oluphambili oluphambili lokumelana neyeza lwesifo sephepha se-mycobacterium lunikezelwe.	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 aphambili 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 noxhathiso lwamachiza kwikhathalogu ye-WHO Mycobacterium yesifo sephepha entsonkothileyo yokuguqulwa kwesifo sephepha, kunye nezinye ezixeliweyo zoxhathiso lwemfuza kunye neendawo zokuguqula amayeza kunye neendawo zophando lwamazwe aphesheya ngokwezibalo zoncwadi lwasekhaya kunye noluncwadi lwamazwe aphesheya.

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 ezilandelelanisa i-high-throughput, kwaye zonke iiplatifomu zokulandelelana zesizukulwana sesibini kunye nesesithathu zingaba phantsi kolandelelwano olunzulu lokufumana ulwazi olulandelelanayo lweejene 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 ngamachiza okanye ukuba sengozini kwamachiza achasene nesifo sephepha kwamiselwa. Idityaniswe nesisombululo sonyango lwesampulu yesikhohlela esizivulayo seMacro & Micro-Test, ingxaki yobuchule obuphantsi be-nucleic acid amplification yeesampulu zesikhohlela saseklinikhi (ubuphinda-phindwe kalishumi kunolo lweendlela zesintu) yasonjululwa, ukuze ukubhaqwa kolandelelwano lokunganyangeki ngamachiza kunokusetyenziswa ngokuthe ngqo kwiisampulu zesikhohlela sezonyango.

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