Chombo Chitsva Chekuongorora Chirwere CheTB uye Kuona Kusashanda Kwemishonga: Kutevedzana Kwakatarwa Kwechizvarwa Chitsva (tNGS) Kwakasanganiswa Nekudzidza Kwemuchina Kwekuongorora Chirwere CheTB Hypersensitivity
Mushumo wemabhuku: CCa: modhi yekuongorora yakavakirwa patNGS uye machine learning, iyo yakakodzera vanhu vane TB isina mabhakitiriya uye meningitis ine tuberculous.
Musoro wenyaya: Kutevedzana kwechizvarwa chinotevera kwakanangana neTB uye kudzidza kwemuchina: nzira yekuongorora ine hungwaru hwepamusoro yemapapu asina kusimba uye meningitis ine tubular.
Periodical: 《Clinica Chimica Acta》
KANA: 6.5
Zuva rekuburitswa: Ndira 2024

Pamwe chete neYunivhesiti yeChinese Academy of Sciences neBeijing Chest Hospital yeCapital Medical University, Macro & Micro-Test yakagadzira modhi yekuongorora chirwere cherurindi yakavakirwa pachizvarwa chitsva chetekinoroji yekutevera (tNGS) uye nzira yekudzidza yemuchina, iyo yakapa mukana wekuona chirwere cherurindi zvakanyanya nemabhakitiriya mashoma uye meningitis yerurindi, yakapa nzira itsva yekuongorora chirwere cherurindi zvakanyanya yekuongorora mhando mbiri dzerurindi, uye yakabatsira kuongororwa kwakarurama, kuona kusapindirana nemishonga uye kurapa chirwere cherurindi. Panguva imwe chete, zvakaonekwa kuti plasma cfDNA yemurwere inogona kushandiswa semhando yakakodzera yemuenzaniso wekurapa mukuongorora TBM.
Muchidzidzo ichi, 227 plasma samples uye cerebrospinal fluid sampuro dzakashandiswa kugadzira ma clinical cohorts maviri, umo sampuli dze laboratory diagnostic cohort dzakashandiswa kugadzira machine learning model yekuongorora chirwere cherurindi, uye sampuli dze clinical diagnostic cohort sampuro dzakashandiswa kusimbisa ma development model yakasimbiswa. Sampuro dzese dzakatanga kunangwa ne targeted targeted capture probe pool ye Mycobacterium tuberculosis. Zvadaro, zvichibva pa TB-tNGS sequencing data, decision tree model inoshandiswa kuita 5-fold cross-validation pa training and validation sets ye laboratory diagnostic queue, uye diagnostic thresholds dze plasma sampuro uye cerebrospinal fluid sampuro dzinowanikwa. Ma threshold akawanikwa anounzwa mu test sets mbiri dze clinical diagnosis queue kuti aonekwe, uye diagnostic performance yemudzidzi inoongororwa ne ROC curve. Pakupedzisira, ma diagnostic model e tuberculosis akawanikwa.

Mufananidzo 1 dhayagiramu yedhizaini yekutsvagisa
Mhedzisiro: Zvichienderana nemiganhu chaiyo yeCSF DNA sample (AUC = 0.974) uye plasma cfDNA sample (AUC = 0.908) zvakawanikwa muchidzidzo ichi, pakati pemasampuli 227, kunzwisiswa kweCSF sample kwaive 97.01%, kunzwisisika kwaive 95.65%, uye kunzwisisika uye kunzwisisika kweplasma sample kwaive 82.61% uye 86.36%. Mukuongorora masampuli 44 eplasma cfDNA necerebrospinal fluid DNA kubva kuvarwere veTBM, nzira yekuongorora yechidzidzo ichi ine kuenderana kwakanyanya kwe90.91% (40/44) muplasma cfDNA necerebrospinal fluid DNA, uye kunzwisisika kwacho kuri 95.45% (42/44). Muvana vane pulmonary tuberculosis, nzira yekuongorora yechidzidzo ichi inonyanya kunzwisiswa nemasampuli eplasma kupfuura mhedzisiro yeXpert yekuongorora masampuli emudumbu kubva kuvarwere vamwe chete (28.57% VS 15.38%).

Mufananidzo 2 Kuongororwa kwekushanda kwemuenzaniso wekuongorora chirwere cherurindi kune vanhu vakawanda

Mufananidzo 3. Mhedzisiro yekuongorora yemasampuli maviri
Mhedziso: Nzira yekuongorora chirwere cherurindi ine kunzwa kwakanyanya yakagadzwa muchidzidzo ichi, iyo inogona kupa chishandiso chekuongorora chirwere chine kunzwa kwakanyanya kwekuona kune varwere vekiriniki vane oligobacillary tuberculosis (negative culture). Kuonekwa kwechirwere cherurindi chine kunzwa kwakanyanya kwakavakirwa paplasma cfDNA kungave mhando yakakodzera yemuenzaniso wekuongorora chirwere cherurindi chine simba uye meningitis yerurindi (plasma samples dziri nyore kuunganidza kupfuura cerebrospinal fluid kune varwere vanofungidzirwa kuti vane chirwere cherurindi cheuropi).
Chinongedzo chekutanga: https://www.sciencedirect.com/science/article/pii/s0009898123004990? via%3Dihub
Sumo pfupi yezvigadzirwa zveMacro & Micro-Test TB series detection
Tichifunga nezvemamiriro ezvinhu akaomarara evarwere veTB uye zvinodiwa zvakasiyana-siyana, Macro & Micro-Test inopa seti yakazara yemhinduro dzeNGS dzekuburitsa mvura kubva mumasampuli emapute, kuvaka nekutevedzana kwerabhurari yeQualcomm, uye kuongorora data. Zvigadzirwa izvi zvinosanganisira kuongororwa nekukurumidza kwevarwere veTB, kuona kuti TB haisi kushanda nemishonga, kunyora mycobacterium tuberculosis neNTM, kuongororwa kwechirwere cheTB chisina mabhakitiriya nevanhu vane tuberculosis, nezvimwewo.
Zvishandiso zvekuongorora TB ne mycobacteria:
| Nhamba yechinhu | zita rechigadzirwa | zviri mukati mekuyedza zvigadzirwa | mhando yemuenzaniso | modhi inoshanda |
| HWTS-3012 | Muenzaniso wekuburitsa mumiriri | Yakashandiswa mukurapa masampuli emakonzo, yakawana nhamba yepamusoro-soro, Sutong Machinery Equipment 20230047. | pfapfaidzo | |
| HWTS-NGS-P00021 | Kiti yekuongorora huwandu hweQualcomm yechirwere cheTB chinokonzerwa nehypersensitivity (nzira yekubata probe) | Kuongororwa kwechirwere cheTB chemapapu chisina kupinda mumuviri (non-invasive biopsy) chechirwere cheTB chemapapu chisina mabhakitiriya uye maronda europi; Mienzaniso yevanhu vanofungidzirwa kuti vane chirwere cheTB kana kuti kwete TB mycobacteria yakaongororwa nekuongorora kwakanyatsojeka metagenomics, uye ruzivo rwekuona kana TB kana kuti kwete TB mycobacteria yakabatwa uye ruzivo rwekutanga rwekuti mycobacterium tuberculosis haibatwi nemishonga rwakapihwa. | Ropa rekunze, mvura yekugezesa mudumbu, hydrothorax neascites, muenzaniso wekuboorwa kweganda, mvura yemusana. | Chizvarwa chechipiri |
| HWTS-NGS-T001 | Mycobacterium typing uye drug resistance detection kit (nzira yekuwedzera masero akawanda) | Kuongororwa kweMycobacterium typing, kusanganisira MTBC ne187 NTM;Kuonekwa kweMycobacterium tuberculosis isingarapike nemishonga kunosanganisira mishonga gumi nemitatu nenzvimbo gumi nematanhatu dzekuchinja kwemajini asingarapike nemishonga. | Sputum, mvura yekugezesa mudumbu, hydrothorax neascites, muenzaniso wekuboorwa kweganda, mvura yemusana. | Chikuva chechipiri/chechitatu chechizvarwa chechipiri |
Zvinonyanya Kukosha: HWTS-NGS-T001 Mycobacterium typing uye drug resistance detection kit (nzira yekuwedzera yakawanda)
Sumo yechigadzirwa
Chigadzirwa ichi chakavakirwa pamishonga mikuru yekutanga neyechipiri inotsanangurwa mugwara reWHO TB, macrolides nemaaminoglycosides anowanzo shandiswa mugwara reNTM rekurapa, uye nzvimbo dzekusagona mishonga dzinofukidza boka rimwe chete renzvimbo dzine chekuita nekusagona mishonga muWHO Mycobacterium tuberculosis complex mutation catalog, pamwe nedzimwe nzvimbo dzakataurwa dzekusagona mishonga uye nzvimbo dzekuchinja zvichienderana nekuferefeta nenhamba dzemabhuku akanyanya kuwanikwa munyika nekune dzimwe nyika.
Kuzivikanwa kwekunyora kwakavakirwa pamhando dzeNTM dzakapfupikiswa mugwara reNTM rakaburitswa neChinese Journal of Tuberculosis and Respiratory Diseases pamwe nekubvumirana kwenyanzvi. Ma primer ekunyora akagadzirwa anogona kuwedzera, kurongeka uye kunyora zvinyorwa zvemhando dzeNTM dzinopfuura 190.
Kuburikidza netekinoroji yekuwedzera huwandu hwemajini eMycobacterium, majini ekugadzira genotyping nemajini asingaurayi mishonga eMycobacterium akawedzerwa nePCR yakawanda, uye musanganiswa weamplicon wemajini anotarisirwa kuonekwa wakawanikwa. Zvigadzirwa zvakawedzera zvinogona kuvakwa mumaraibhurari ekutevera echizvarwa chechipiri kana chechitatu, uye mapuratifomu ese ekutevera echizvarwa chechipiri nechechitatu anogona kuongororwa zvakadzama kuti awane ruzivo rwekutevera kwemajini anotarisirwa. Nekuenzanisa nekuchinja kunozivikanwa kuri mu database yakavakirwa mukati (kusanganisira WHO Mycobacterium tuberculosis complex mutation catalog uye hukama hwayo nekusaradzikwa kwemishonga), kuchinja kwakabatana nekusaradzikwa kwemishonga kana kubatwa nemishonga yekurwisa TB kwakaongororwa. Pamwe chete nemhinduro yekurapa sputum sample yakavhurwa yega yeMacro & Micro-Test, dambudziko rekusaradzikwa kwe nucleic acid kwe clinical sputum samples (yakapetwa kagumi kupfuura yenzira dzechinyakare) rakagadziriswa, kuitira kuti kuongororwa kwekusaradzikwa kwemishonga kunogona kushandiswa zvakananga kumasampuli ema sputum ekiriniki.
Rudzi rwekuona chigadzirwa
34majini ane chekuita nekusagona kushandisa mishonga18mishonga yekurwisa TB uye6Mishonga yeNTM yakawanikwa, ichifukidza297nzvimbo dzisingarapike mishonga; Mhando gumi dzeMycobacterium tuberculosis nezvimwe zvinopfuura190mhando dzeNTM dzakaonekwa.


Tafura 1: Ruzivo rweMishonga yeVane Makore 18+6 +190+NTM
Kubatsira kwechigadzirwa
Kugona kuchinjika kwakasimba mukurapa: sampuro dzemapute dzinogona kuonekwa zvakananga nemushonga wekuzvinyungudutsa usina kucheneswa.
Kuedza kuri nyore: danho rekutanga rekuwedzera simba riri nyore, uye kuvaka raibhurari kunopedzwa mumaawa matatu, izvo zvinovandudza kushanda zvakanaka kwebasa.
Kunyora kwakazara uye kuramba kushandisa mishonga: kufukidza nzvimbo dzekunyora uye kuramba kushandisa mishonga dzeMTB neNTM, idzo dziri pfungwa huru dzekunetseka nekurapa, kuona kunyora kwakarurama uye kuramba kushandisa mishonga, kutsigira software yekuongorora yakazvimirira, uye kugadzira mishumo yekuongorora nekudzvanya kamwe chete.
Kuenderana: kuenderana kwechigadzirwa, kuchienderana nemapuratifomu makuru eILM neMGI/ONT.
Tsanangudzo yechigadzirwa
| Kodhi yechigadzirwa | zita rechigadzirwa | Chikuva chekuona | tsanangudzo |
| HWTS-NGS-T001 | Mycobacterium typing uye drug resistance kit (nzira yekuwedzera yakawanda) | ONT, Illumina, MGI, Salus pro | 16/96rxn |
Nguva yekutumira: Ndira-23-2024