Kev kuaj DNA methylation ua ke nrog cov xov tooj ntse rau kev kuaj mob qog nqaij hlav thiab kev kuaj mob leukaemia thaum ntxov nrog qhov tseeb ntawm 90.0%!

Kev kuaj mob qog noj ntshav thaum ntxov los ntawm kev siv cov kua kuaj ntshav yog ib txoj kev tshiab ntawm kev kuaj mob qog noj ntshav thiab kev kuaj mob uas tau tsim los ntawm Lub Koom Haum Kab Mob Qog Noj Ntshav Hauv Tebchaws Meskas hauv xyoo tas los no, nrog lub hom phiaj ntawm kev kuaj mob qog noj ntshav thaum ntxov lossis txawm tias cov qog ua ntej mob qog noj ntshav. Nws tau siv dav ua ib qho cim tshiab rau kev kuaj mob qog noj ntshav thaum ntxov ntawm ntau yam kab mob qog noj ntshav, suav nrog mob qog noj ntshav ntsws, mob qog noj ntshav hauv plab hnyuv, mob qog ntshav gliomas thiab mob qog noj ntshav poj niam.

Qhov tshwm sim ntawm cov platforms los txheeb xyuas cov methylation landscape (Methylscape) biomarkers muaj peev xwm los txhim kho qhov kev tshuaj ntsuam mob qog noj ntshav thaum ntxov, muab cov neeg mob rau theem kho tau sai tshaj plaws.

Tsis ntev los no, cov kws tshawb fawb tau tsim ib lub platform yooj yim thiab ncaj qha rau kev ntes methylation toj roob hauv pes raws li cysteamine dai kom zoo nkauj kub nanoparticles (Cyst / AuNPs) ua ke nrog lub xov tooj ntawm tes biosensor uas ua rau muaj kev tshuaj ntsuam sai sai ntawm ntau yam qog nqaij hlav. Kev tshuaj ntsuam thaum ntxov rau leukaemia tuaj yeem ua tiav hauv 15 feeb tom qab DNA rho tawm los ntawm cov qauv ntshav, nrog qhov tseeb ntawm 90.0%. Lub npe ntawm tsab xov xwm yog Kev ntes sai ntawm cov qog nqaij hlav DNA hauv tib neeg cov ntshav siv cysteamine-capped AuNPs thiab lub xov tooj ntawm tes kawm tshuab.

Daim Duab 1. Ib lub platform yooj yim thiab ceev ceev rau kev kuaj mob qog noj ntshav los ntawm cov khoom Cyst/AuNPs tuaj yeem ua tiav hauv ob kauj ruam yooj yim.

Qhov no tau pom hauv Daim Duab 1. Ua ntej, cov kua dej tau siv los yaj cov DNA tawg. Tom qab ntawd Cyst/AuNPs tau ntxiv rau hauv cov kua sib xyaw. DNA ib txwm thiab malignant muaj cov yam ntxwv methylation sib txawv, ua rau cov DNA tawg nrog cov qauv sib dhos sib txawv. DNA ib txwm sib sau ua ke xoob thiab thaum kawg sib sau ua ke Cyst/AuNPs, uas ua rau Cyst/AuNPs hloov xim liab, yog li qhov kev hloov xim ntawm liab mus rau ntshav tuaj yeem pom nrog lub qhov muag liab qab. Qhov sib txawv, qhov tshwj xeeb methylation profile ntawm mob qog noj ntshav ua rau muaj cov pawg loj dua ntawm cov DNA tawg.

Cov duab ntawm 96-qhov phaj tau raug coj los ntawm kev siv lub koob yees duab smartphone. Cov DNA mob qog noj ntshav tau ntsuas los ntawm lub xov tooj ntse uas muaj kev kawm tshuab piv rau cov txheej txheem raws li spectroscopy.

Kev kuaj mob qog noj ntshav hauv cov qauv ntshav tiag tiag

Yuav kom txuas ntxiv qhov siv tau ntawm lub platform sensing, cov kws tshawb nrhiav tau siv lub sensor uas ua tiav qhov sib txawv ntawm cov DNA ib txwm thiab cov DNA mob qog noj ntshav hauv cov qauv ntshav tiag tiag. Cov qauv methylation ntawm CpG qhov chaw epigenetically tswj hwm kev qhia tawm ntawm cov noob caj noob ces. Hauv yuav luag txhua hom mob qog noj ntshav, kev hloov pauv hauv DNA methylation thiab yog li ntawd hauv kev qhia tawm ntawm cov noob caj noob ces uas txhawb nqa tumorigenesis tau pom tias hloov pauv.

Ua ib qho qauv rau lwm yam mob qog noj ntshav uas cuam tshuam nrog DNA methylation, cov kws tshawb fawb tau siv cov qauv ntshav los ntawm cov neeg mob leukaemia thiab cov neeg noj qab haus huv los tshawb nrhiav qhov ua tau zoo ntawm cov toj roob hauv pes methylation hauv kev sib txawv ntawm cov mob qog noj ntshav leukaemic. Cov cim qhia txog methylation toj roob hauv pes no tsis yog tsuas yog ua tau zoo dua li cov txheej txheem tshuaj ntsuam mob leukaemia sai uas twb muaj lawm, tab sis kuj qhia txog qhov ua tau ntawm kev nthuav dav mus rau kev kuaj pom ntxov ntawm ntau yam mob qog noj ntshav siv qhov kev sim yooj yim thiab ncaj nraim no.

DNA los ntawm cov qauv ntshav los ntawm 31 tus neeg mob leukaemia thiab 12 tus neeg noj qab haus huv tau raug soj ntsuam. raws li pom hauv daim duab hauv daim duab 2a, qhov nqus ntawm cov qauv mob qog noj ntshav (ΔA650/525) qis dua li ntawm DNA los ntawm cov qauv ib txwm muaj. qhov no feem ntau yog vim muaj hydrophobicity ua rau muaj kev sib sau ua ke ntawm cov DNA mob qog noj ntshav, uas tiv thaiv kev sib sau ua ke ntawm Cyst/AuNPs. Yog li ntawd, cov nanoparticles no tau tawg tag nrho hauv cov txheej sab nraud ntawm cov pob zeb qog noj ntshav, uas ua rau muaj kev sib cais sib txawv ntawm Cyst/AuNPs adsorbed ntawm cov DNA ib txwm muaj thiab cov pob zeb qog noj ntshav. Cov kab ROC ces tau tsim los ntawm kev hloov pauv qhov txwv ntawm tus nqi tsawg kawg nkaus ntawm ΔA650/525 mus rau tus nqi siab tshaj plaws.

Daim Duab 2.(a) Cov nqi absorbance sib piv ntawm cov kua cyst/AuNPs uas qhia txog qhov muaj cov DNA ib txwm (xiav) thiab mob qog noj ntshav (liab) nyob rau hauv cov xwm txheej zoo tshaj plaws.

(DA650/525) ntawm cov phiaj xwm thawv; (b) ROC kev tshuaj xyuas thiab kev ntsuam xyuas ntawm kev kuaj mob. (c) Confusion matrix rau kev kuaj mob ntawm cov neeg mob ib txwm thiab cov neeg mob qog noj ntshav. (d) Kev rhiab heev, qhov tshwj xeeb, tus nqi kwv yees zoo (PPV), tus nqi kwv yees tsis zoo (NPV) thiab qhov tseeb ntawm txoj kev tsim kho.

Raws li pom hauv Daim Duab 2b, thaj chaw nyob hauv qab ROC nkhaus (AUC = 0.9274) tau txais rau lub sensor tsim tau qhia txog kev rhiab heev thiab kev tshwj xeeb. Raws li pom tau los ntawm lub thawv plot, qhov chaw qis tshaj plaws uas sawv cev rau pawg DNA ib txwm tsis sib cais zoo los ntawm qhov chaw siab tshaj plaws uas sawv cev rau pawg DNA mob qog noj ntshav; yog li ntawd, logistic regression tau siv los sib txawv ntawm cov pab pawg ib txwm thiab mob qog noj ntshav. Muab ib pawg ntawm cov hloov pauv ywj pheej, nws kwv yees qhov tshwm sim ntawm qhov xwm txheej tshwm sim, xws li mob qog noj ntshav lossis pab pawg ib txwm. Cov hloov pauv nyob ntawm ntau ntawm 0 thiab 1. Yog li ntawd, qhov tshwm sim yog qhov tshwm sim. Peb tau txiav txim siab qhov tshwm sim ntawm kev txheeb xyuas mob qog noj ntshav (P) raws li ΔA650 / 525 raws li hauv qab no.

qhov twg b = 5.3533, w1 = -6.965. Rau kev faib cov qauv, qhov muaj feem tsawg dua 0.5 qhia txog cov qauv ib txwm muaj, thaum qhov muaj feem ntawm 0.5 lossis siab dua qhia txog cov qauv mob qog noj ntshav. Daim duab 2c qhia txog qhov kev tsis meej pem matrix tsim los ntawm kev tso-nws-nyob ib leeg cross-validation, uas tau siv los xyuas qhov ruaj khov ntawm txoj kev faib tawm. Daim duab 2d qhia txog kev ntsuam xyuas kev kuaj mob ntawm txoj kev, suav nrog kev rhiab heev, qhov tshwj xeeb, tus nqi kwv yees zoo (PPV) thiab tus nqi kwv yees tsis zoo (NPV).

Cov biosensors uas siv tau rau ntawm Smartphone

Yuav kom yooj yim dua rau kev kuaj cov qauv yam tsis siv cov spectrophotometers, cov kws tshawb fawb tau siv kev txawj ntse cuav (AI) los txhais cov xim ntawm cov tshuaj thiab paub qhov txawv ntawm cov neeg ib txwm thiab cov neeg mob qog noj ntshav. Muab qhov no, kev pom computer tau siv los txhais cov xim ntawm cov tshuaj Cyst/AuNPs rau hauv DNA ib txwm (ntshav) lossis DNA mob qog noj ntshav (liab) siv cov duab ntawm 96-qhov phaj uas tau thaij los ntawm lub koob yees duab xov tooj ntawm tes. Kev txawj ntse cuav tuaj yeem txo cov nqi thiab txhim kho kev nkag mus tau hauv kev txhais cov xim ntawm cov tshuaj nanoparticle, thiab yam tsis tas siv cov khoom siv kho qhov muag ntawm lub xov tooj ntawm tes. Thaum kawg, ob lub qauv kev kawm tshuab, suav nrog Random Forest (RF) thiab Support Vector Machine (SVM) tau kawm los tsim cov qauv. ob qho tib si RF thiab SVM qauv tau faib cov qauv kom raug raws li qhov zoo thiab qhov tsis zoo nrog qhov tseeb ntawm 90.0%. Qhov no qhia tau hais tias kev siv kev txawj ntse cuav hauv kev siv xov tooj ntawm tes biosensing yog qhov ua tau heev.

Daim Duab 3.(a) Chav kawm ntawm cov tshuaj uas tau sau tseg thaum lub sijhawm npaj cov qauv rau kauj ruam nrhiav duab. (b) Piv txwv li daim duab uas tau thaij thaum lub sijhawm nrhiav duab. (c) Xim ntawm cov tshuaj cyst/AuNPs hauv txhua lub qhov ntawm 96-qhov phaj uas tau rho tawm ntawm daim duab (b).

Siv Cyst/AuNPs, cov kws tshawb fawb tau ua tiav tsim ib lub platform yooj yim rau kev ntes methylation landscape thiab lub sensor uas muaj peev xwm paub qhov txawv ntawm DNA ib txwm thiab DNA mob qog noj ntshav thaum siv cov qauv ntshav tiag tiag rau kev kuaj mob leukaemia. Lub sensor tsim tau qhia tias DNA rho tawm ntawm cov qauv ntshav tiag tiag muaj peev xwm ntes tau me me ntawm cov DNA mob qog noj ntshav (3nM) hauv cov neeg mob leukaemia hauv 15 feeb, thiab qhia qhov tseeb ntawm 95.3%. Txhawm rau kom yooj yim dua rau kev kuaj cov qauv los ntawm kev tshem tawm qhov xav tau spectrophotometer, kev kawm tshuab tau siv los txhais cov xim ntawm cov kua thiab sib txawv ntawm cov neeg ib txwm thiab cov neeg mob qog noj ntshav siv daim duab xov tooj ntawm tes, thiab qhov tseeb kuj tuaj yeem ua tiav ntawm 90.0%.

Siv: DOI: 10.1039/d2ra05725e