ʻO kahi mea kaua hou no ka hōʻoia ʻana i ka maʻi maʻi a me ka ʻike ʻana i ka lāʻau kūʻē i ka lāʻau: He Generation Targeted Sequencing (tNGS) i hui pū ʻia me ke aʻo mīkini no ka maʻi maʻi hypersensitivity.
Hōʻike moʻokalaleo: CCa: he kumu hoʻohālike diagnostic e pili ana i ka tNGS a me ke aʻo ʻana i ka mīkini, kūpono i ka poʻe me ka maʻi maʻi maʻi liʻiliʻi a me ka maningitis tuberculous.
Thesis title: Tuberculous-targeted next-generation sequencing and machine learning: he ultra-sensitive diagnostic strategy for paucific pulmonary tubulars and tubular meningitis.
Manawa: 《Clinica Chimica Acta》
IF:6.5
Ka lā i paʻi ʻia: Ianuali 2024
Hoʻohui pū ʻia me ke Kulanui o Kina Academy of Science a me Beijing Chest Hospital o Capital Medical University, ua hoʻokumu ʻo Macro & Micro-Test i kahi hiʻohiʻona maʻi maʻi maʻi e pili ana i ka ʻenehana hou o ka ʻenehana i hoʻopaʻa ʻia (tNGS) a me ke ʻano aʻo mīkini, kahi i hāʻawi i ka ʻike kiʻekiʻe kiʻekiʻe no ka maʻi maʻi me ka liʻiliʻi o ka bacteria a me ka maningitis tuberculous, hāʻawi ʻia i ke ʻano o ka maʻi maʻi maʻi maʻi a me ke ʻano o ka maʻi maʻi maʻi. ʻike kūʻē i ka lāʻau a me ka mālama ʻana i ka maʻi maʻi. I ka manawa like, ʻike ʻia e hiki ke hoʻohana ʻia ka cfDNA plasma o ka mea maʻi ma ke ʻano he ʻano laʻana kūpono no ka hoʻāʻo ʻana i ka maʻi ma ka ʻike ʻana o ka TBM.
I loko o kēia noiʻi ʻana, ua hoʻohana ʻia nā 227 plasma samples a me ka cerebrospinal fluid samples no ka hoʻokumu ʻana i ʻelua cohorts clinical, kahi i hoʻohana ai ka laboratory diagnostic cohort samples no ka hoʻokumu ʻana i ka mīkini aʻo kumu o ka maʻi maʻi maʻi, a ua hoʻohana ʻia nā hōʻailona diagnostic cohort e hōʻoia i ke kumu hoʻohālike i hoʻokumu ʻia. Ua hoʻopaʻa mua ʻia nā laʻana a pau e kahi pūnāwai hopu hopu no ka Mycobacterium tuberculosis. A laila, ma muli o ka TB-tNGS sequencing data, ua hoʻohana ʻia ke kumu hoʻoholo kumu lāʻau e hana i 5-fold cross-validation ma ka hoʻomaʻamaʻa ʻana a me ka hōʻoia ʻana o ka queue diagnostic laboratory, a loaʻa nā paepae diagnostic o nā laʻana plasma a me nā ʻano wai cerebrospinal. Lawe ʻia ka paepae i loaʻa i loko o ʻelua pūʻulu hoʻāʻo o ka queue diagnostic clinical no ka ʻike ʻana, a loiloi ʻia ka hana diagnostic o ka mea aʻo e ka pihi ROC. ʻO ka hope loa, ua loaʻa ke kumu hoʻohālike o ka maʻi maʻi.
Fig. 1 schematic diagram of research design
Nā hualoaʻa: E like me nā paepae kiko'ī o ka CSF DNA sample (AUC = 0.974) a me ka plasma cfDNA sample (AUC = 0.908) i hoʻoholoʻia i loko o kēia haʻawina, ma waena o 227 mau hōʻailona,ʻo ka sensitivity o ka CSF sample he 97.01%, he 95.65% ka kiko'ī, a he 95.65% ka mea kiko'ī, a he 95.65% ka sensitivity a me ka kiko'ī o ka plasma 8.62%. I ka anaana o 44 paired Eia kekahi laʻana o ka plasma cfDNA a me ka cerebrospinal wai DNA mai TBM maʻi, i ka diagnostic hoʻolālā o keia haʻawina he kiʻekiʻe kūlike o 90.91% (40/44) i ka plasma cfDNA a me ka cerebrospinal wai DNA, a me ka sensitivity o 95.45% (42/44). I na keiki me ka ma'i ma'i pulmonary, 'oi aku ka ma'alahi o ka ho'olālā diagnostic o kēia ha'awina i nā la'ana plasma ma mua o nā hualoa'a 'ike Xpert o nā hō'ailona wai'ōpū mai nā ma'i like (28.57% VS 15.38%).
2 Fig
Fig. 3 Nā hualoaʻa diagnostic o nā laʻana i hoʻopaʻa ʻia
Ka hopena: Ua hoʻokumu ʻia kahi ʻano diagnostic hypersensitive no ka tuberculosis, hiki ke hāʻawi i kahi mea hana diagnostic me ka ʻike kiʻekiʻe loa no nā maʻi maʻi me ka oligobacillary tuberculosis (negative culture). ʻO ka ʻike ʻana i ka maʻi maʻi hypersensitive e pili ana i ka plasma cfDNA he ʻano laʻana kūpono paha no ka ʻike ʻana i ka maʻi maʻi maʻi maʻi a me ka maʻi maʻi maʻi (ʻoi aku ka maʻalahi o ka hōʻiliʻili ʻana o nā laʻana plasma ma mua o ka wai cerebrospinal no nā maʻi i manaʻo ʻia he maʻi maʻi lolo).
Ka loulou kumu: https://www.sciencedirect.com/science/article/pii/s0009898123004990? ma o%3Dihub
Hoʻopuka pōkole o nā huahana ʻike maka o ka Macro & Micro-Test tuberculosis series
Ma ka nānā ʻana i ke kūlana laʻana paʻakikī o nā maʻi maʻi maʻi maʻi a me nā pono like ʻole, hāʻawi ʻo Macro & Micro-Test i kahi pūʻulu piha o nā hāmeʻa NGS no ka unuhi ʻana i ka wai mai nā laʻana sputum, kūkulu hale waihona Qualcomm a me ka hoʻonohonoho ʻana, a me ka nānā ʻana i ka ʻikepili. Hoʻopili nā huahana i ka ʻike wikiwiki o nā maʻi maʻi maʻi, ka ʻike ʻana i ka lāʻau kūʻē i ka maʻi maʻi, ke kākau ʻana i ka mycobacterium tuberculosis a me NTM, hypersensitivity diagnostic o bacteria-negative tuberculosis a me nā kānaka tuberculous, etc.
Nā pahu ʻike maka no ka maʻi maʻi a me ka mycobacteria:
| 'ikamu helu | inoa huahana | maʻiʻo hoʻāʻo huahana | ʻano hāpana | kumu hoʻohālike pili |
| HWTS-3012 | Mea hoʻokuʻu laʻana | Hoʻohana ʻia i ka hoʻomaʻamaʻa liquefaction o nā laʻana sputum, ua loaʻa i kahi helu helu papa mua, Sutong Machinery Equipment 20230047. | ʻūhā | |
| HWTS-NGS-P00021 | ʻO ka pahu ʻike helu Qualcomm no ka maʻi maʻi hypersensitive (ke ʻano hopu hopu) | Non-invasive (liquid biopsy) hypersensitivity detection for bacteria-negative pulmonary tuberculosis and brain nodules; ʻO nā laʻana o ka poʻe i manaʻo ʻia ua loaʻa i ka maʻi maʻi a i ʻole ka mycobacteria non-tuberculosis i kālailai ʻia e ka metagenomics sequencing hohonu, a ua hāʻawi ʻia ka ʻike ʻike o ka maʻi tuberculosis a i ʻole ka maʻi maʻi mycobacteria a ua hāʻawi ʻia ka ʻike kūʻē lāʻau mua o ka mycobacterium tuberculosis. | ʻO ke koko pili, ka wai holoi alveolar, hydrothorax a me nā ascites, ka laʻana puncture kikoʻī, ka wai cerebrospinal. | ʻO ka hanauna ʻelua |
| HWTS-NGS-T001 | Mycobacterium typing and drug resistance detection kit (multiplex amplification sequencing method) | ʻO ka hoʻāʻo ʻana o ka Mycobacterium type, me MTBC a me 187 NTM；ʻO ka ʻike kūʻē ʻana i ka lāʻau lapaʻau o Mycobacterium tuberculosis e uhi ana i nā lāʻau lapaʻau 13 a me 16 mau kahua mutation kumu o nā genes kūʻē i ka lāʻau. | Sputum, alveolar lavage wai, hydrothorax a me ascites, hāpana puncture kiko, wai cerebrospinal. | ʻElua/kolu o ka hanauna lua paepae |
Nā mea koʻikoʻi: HWTS-NGS-T001 Mycobacterium typing and drug resistance detection kit (multiplex amplification method)
Hoʻolauna huahana
Hoʻokumu ʻia ka huahana ma luna o nā lāʻau lapaʻau mua a me ka lua i wehewehe ʻia ma nā alakaʻi lapaʻau ʻo WHO TB, macrolides a me aminoglycosides i hoʻohana mau ʻia i nā alakaʻi lapaʻau NTM, a ʻo nā kahua kūʻē lāʻau e uhi i nā pūʻulu āpau e pili ana i ka lāʻau lapaʻau i ka WHO Mycobacterium tuberculosis complex mutation catalogue, a me nā mea ʻē aʻe i hōʻike ʻia i nā genes kū'ē lāʻau a me nā pae hoʻopaʻapaʻa home e like me nā palapala noiʻi o ka home.
Hoʻokumu ʻia ka ʻike paʻi ʻana ma nā kaha NTM i hōʻuluʻulu ʻia ma nā alakaʻi NTM i paʻi ʻia e ka Chinese Journal of Tuberculosis and Respiratory Diseases a me ka ʻae ʻana o nā loea. Hiki ke hoʻonui, hoʻonohonoho a hoʻokaʻawale i nā ʻano ʻano NTM ma mua o 190.
Ma o ka ʻenehana hoʻonui PCR multiplex i hoʻopaʻa ʻia, ua hoʻonui ʻia nā genes genotyping a me nā genes kū'ē i ka lāʻau o Mycobacterium e ka PCR multiplex, a ua loaʻa ka hui amplicon o nā genes i ʻike ʻia. Hiki ke kūkulu ʻia nā huahana i hoʻonui ʻia i loko o ka lua o ka hanauna a i ʻole ke kolu o ka hanauna kiʻekiʻe-throughput sequencing hale waihona puke, a hiki ke hoʻokau ʻia nā papa hana sequencing o ka lua a me ke kolu o ka hanauna i ka sequencing hohonu no ka loaʻa ʻana o ka ʻike sequence o nā genes target. Ma ka hoʻohālikelike ʻana me nā hoʻololi i ʻike ʻia i loko o ka waihona kuhikuhi i kūkulu ʻia (me ka WHO Mycobacterium tuberculosis complex mutation catalog a me kona pilina me ke kūʻē ʻana i ka lāʻau lapaʻau), ua hoʻoholo ʻia nā hoʻololi e pili ana i ke kūʻē ʻana i ka lāʻau a i ʻole ka maʻalahi o nā lāʻau anti-tuberculosis. Hoʻohui pū ʻia me ka hāmama ʻana o ka sputum sample lapaʻau o ka Macro & Micro-Test, ua hoʻoholo ʻia ka pilikia o ka haʻahaʻa nucleic acid amplification efficiency of clinical sputum samples (he ʻumi mau manawa kiʻekiʻe ma mua o nā ʻano kuʻuna), no laila hiki ke hoʻopili pololei ʻia ka ʻike ʻana i ka lāʻau lapaʻau i nā hōʻailona sputum.
Laulā ʻike huahana
34lāʻau kū'ē-pili genes o18lāʻau anti-tuberculosis a6Ua ʻike ʻia nā lāʻau lapaʻau NTM, uhi297nā kahua kūʻē lāʻau; He ʻumi ʻano o ka Mycobacterium tuberculosis a ʻoi aku190Ua ʻike ʻia nā ʻano NTM.
Papa 1: ʻIkepili o 18+6 Lapaʻau +190+NTM
Pono huahana
ʻO ka hiki ke hoʻololi i ka maʻi maʻi: hiki ke ʻike pololei ʻia nā laʻana sputum me ka mea hoʻoheheʻe ponoʻī me ka ʻole o ka moʻomeheu.
He mea maʻalahi ka hana hoʻokolohua: maʻalahi ka hana mua o ka amplification, a ua hoʻopau ʻia ka hale waihona puke i nā hola 3, e hoʻomaikaʻi ai i ka hana pono.
ʻO ka paʻi paʻi piha ʻana a me ke kūʻē ʻana i ka lāʻau lapaʻau: e uhi ana i nā kahua paʻi a me ke kūʻē ʻana i ka lāʻau o MTB a me NTM, ʻo ia nā mea nui o ka hopohopo lapaʻau, ka paʻi pololei ʻana a me ka ʻike kūʻē ʻana i ka lāʻau, ke kākoʻo ʻana i nā polokalamu loiloi kūʻokoʻa, a me ka hoʻopuka ʻana i nā hōʻike loiloi me hoʻokahi kaomi.
Hoʻohālikelike: hoʻohālikelike huahana, hoʻololi i nā kahua ILM a me MGI/ONT.
Hōʻike huahana
| Code huahana | inoa huahana | kahua ʻike | kikoʻī |
| HWTS-NGS-T001 | Mycobacterium typing and drug resistance detection kit (multiplex amplification method) | ONT, Illumina, MGI, Salus pro | 16/96rxn |
Ka manawa hoʻouna: Jan-23-2024