Gwajin methylation na DNA haɗe tare da wayoyi don fara tantance ciwace-ciwace da cutar sankarar bargo tare da daidaiton 90.0%!

Gano cutar kansa da wuri bisa ga biopsy wani sabon alkibla ne na gano cutar kansa da kuma gano cutar da Cibiyar Ciwon daji ta Amurka ta gabatar a cikin 'yan shekarun nan, da nufin gano ciwon daji da wuri ko ma raunukan da suka riga ya faru. An yi amfani da shi a ko'ina a matsayin wani labari mai ƙididdigewa don gano farkon ganewar cututtuka daban-daban, ciki har da ciwon huhu, ciwon ciki, gliomas da ciwan mahaifa.

Fitowar dandamali don gano methylation shimfidar wuri (Methylscape) biomarkers yana da yuwuwar inganta haɓaka binciken farko na ciwon daji, yana sanya marasa lafiya a matakin farko da za a iya magance su.

Kwanan nan, masu bincike sun haɓaka dandamali mai sauƙi kuma kai tsaye don gano wuri mai faɗi na methylation dangane da cysteamine da aka yi wa ado na nanoparticles na gwal (Cyst/AuNPs) haɗe tare da biosensor na tushen wayar hannu wanda ke ba da damar saurin yin gwajin farko na nau'ikan ciwace-ciwace. Ana iya yin gwajin farko don cutar sankarar bargo a cikin mintuna 15 bayan an cire DNA daga samfurin jini, tare da daidaiton 90.0%. Taken labarin shine Gano gaggawar gano cutar kansa DNA a cikin jinin ɗan adam ta amfani da AuNPs mai ɗauke da cysteamine da wayar hannu da ke iya koyo.

Hoto 1. Za a iya cika dandamali mai sauƙi da sauri don gano cutar kansa ta hanyar abubuwan Cyst/AuNPs a cikin matakai biyu masu sauƙi.

Ana nuna wannan a cikin Hoto na 1. Da farko, an yi amfani da maganin ruwa mai ruwa don narkar da gutsuwar DNA. Sannan an ƙara Cyst/AuNPs zuwa gaurayen maganin. DNA na al'ada da m suna da kaddarorin methylation daban-daban, wanda ke haifar da gutsuttsuran DNA tare da tsarin haɗin kai daban-daban. DNA na al'ada yana tattarawa a hankali kuma a ƙarshe yana haɗa Cyst/AuNPs, wanda ke haifar da yanayin ja-jajayen Cyst/AuNPs, ta yadda za a iya ganin canjin launi daga ja zuwa purple da ido tsirara. Sabanin haka, keɓaɓɓen bayanin martaba na methylation na DNA na kansa yana haifar da samar da manyan gungu na gutsuttsuran DNA.

An dauki hotunan faranti mai rijiyoyi 96 ta hanyar amfani da kyamarar wayar salula. An auna DNA ta kansa ta hanyar wayar hannu sanye take da koyan inji idan aka kwatanta da hanyoyin tushen gani.

Binciken ciwon daji a cikin samfuran jini na gaske

Don tsawaita amfani da dandamalin ji, masu binciken sun yi amfani da firikwensin da ya sami nasarar bambanta tsakanin DNA na al'ada da ciwon daji a cikin samfuran jini na gaske. Hanyoyin methylation a shafukan CpG na epigenetically suna daidaita maganganun kwayoyin halitta. A cikin kusan dukkanin nau'in ciwon daji, canje-canje a cikin DNA methylation kuma don haka a cikin maganganun kwayoyin halitta da ke inganta tumourigenesis an lura da su a madadin.

A matsayin abin koyi ga sauran cututtukan daji da ke da alaƙa da DNA methylation, masu binciken sun yi amfani da samfuran jini daga masu cutar sankarar bargo da kuma kula da lafiya don bincika tasirin yanayin methylation a cikin bambance-bambancen cutar sankarar bargo. Wannan methylation shimfidar wuri biomarker ba wai kawai ya ƙetare hanyoyin gwajin cutar sankarar bargo da ake da su ba, har ma yana nuna yuwuwar faɗaɗa zuwa farkon gano cututtukan daji da yawa ta amfani da wannan ƙima mai sauƙi kuma madaidaiciya.

An yi nazarin DNA daga samfuran jini daga masu cutar sankarar bargo 31 da mutane 12 masu lafiya. kamar yadda aka nuna a cikin akwatin akwatin a cikin Hoto 2a, ƙwaƙwalwar dangi na samfurori na ciwon daji (ΔA650/525) ya kasance ƙasa da na DNA daga samfurori na al'ada. wannan ya faru ne saboda haɓakar haɓakar hydrophobicity wanda ke haifar da tarin ƙwayar cutar kansar DNA, wanda ya hana haɗuwar Cyst/AuNPs. A sakamakon haka, waɗannan nanoparticles sun watse gaba ɗaya a cikin sassan waje na tarin ciwon daji, wanda ya haifar da tarwatsawa daban-daban na Cyst/AuNPs da aka tallata akan al'ada da tarin DNA na kansa. Daga nan aka samar da layukan ROC ta hanyar sãɓãwar ƙofa daga mafi ƙarancin ƙimar ΔA650/525 zuwa matsakaicin ƙima.

Hoto 2.(a) Ƙimar shayarwar dangi na mafita na cyst/AuNPs yana nuna kasancewar al'ada (blue) da ciwon daji (ja) dna a ƙarƙashin ingantattun yanayi

(DA650/525) na filayen akwatin; (b) ROC bincike da kimanta gwaje-gwajen bincike. (c) Matrix mai rikicewa don ganewar asali na al'ada da marasa lafiya na ciwon daji. (d) Hankali, ƙayyadaddun ƙayyadaddun ƙima, ƙimar tsinkaya mai kyau (PPV), ƙimar tsinkaya mara kyau (NPV) da daidaiton hanyar da aka haɓaka.

Kamar yadda aka nuna a cikin Hoto 2b, yankin da ke ƙarƙashin ROC curve (AUC = 0.9274) da aka samu don firikwensin haɓaka ya nuna babban hankali da ƙayyadaddun bayanai. Kamar yadda za a iya gani daga makircin akwatin, mafi ƙasƙanci da ke wakiltar ƙungiyar DNA ta al'ada ba ta rabu da kyau daga matsayi mafi girma da ke wakiltar rukunin DNA na ciwon daji; sabili da haka, an yi amfani da farfadowa na logistic don bambanta tsakanin ƙungiyoyin al'ada da ciwon daji. Idan aka ba da saitin sauye-sauye masu zaman kansu, yana ƙididdige yiwuwar faruwar wani abu, kamar ciwon daji ko ƙungiyar al'ada. Madaidaicin abin dogara yana tsakanin 0 da 1. Sakamakon haka shine yuwuwar. Mun ƙaddara yiwuwar gano cutar kansa (P) bisa ΔA650/525 kamar haka.

inda b=5.3533,w1=-6.965. Don rarraba samfurin, yiwuwar kasa da 0.5 yana nuna samfurin al'ada, yayin da yiwuwar 0.5 ko mafi girma yana nuna samfurin ciwon daji. Hoto na 2c yana nuna matrix ɗin ruɗani da aka haifar daga haƙƙin haƙƙin barin-shi-kaɗai, wanda aka yi amfani da shi don tabbatar da kwanciyar hankali na hanyar rarrabawa. Hoto na 2d yana taƙaita ƙimar gwajin bincike na hanyar, gami da hankali, ƙayyadaddun ƙayyadaddun ƙima, ƙimar tsinkaya mai kyau (PPV) da ƙimar tsinkaya mara kyau (NPV).

Abubuwan biosensor na tushen wayo

Don ƙara sauƙaƙe gwajin samfurin ba tare da yin amfani da na'urorin spectrophotometers ba, masu binciken sunyi amfani da basirar wucin gadi (AI) don fassara launi na maganin da kuma bambanta tsakanin mutane na yau da kullum da masu ciwon daji. Ganin wannan, an yi amfani da hangen nesa na kwamfuta don fassara launi na maganin Cyst/AuNPs zuwa DNA ta al'ada (purple) ko DNA mai ciwon daji (ja) ta amfani da hotunan faranti 96 da aka ɗauka ta hanyar kyamarar wayar hannu. Hankali na wucin gadi na iya rage farashi da haɓaka samun dama ga fassarar launi na mafita na nanoparticle, kuma ba tare da amfani da kowane na'urorin wayar salula na gani ba. A ƙarshe, an horar da nau'ikan koyan inji guda biyu, gami da Random Forest (RF) da Injin Tallafin Vector (SVM) don gina samfuran. duka samfuran RF da SVM sun rarraba samfuran daidai da inganci da mara kyau tare da daidaiton 90.0%. Wannan yana nuna cewa yin amfani da hankali na wucin gadi a cikin binciken biosensing na wayar hannu abu ne mai yiwuwa.

Hoto 3. (a) Matsayin manufa na bayani da aka rubuta a lokacin shirye-shiryen samfurin don mataki na samo hoton. (b) Hoton misalin da aka ɗauka yayin matakin sayan hoton. (c) Ƙarfin launi na maganin cyst/AuNPs a kowace rijiyar farantin rijiyar 96 da aka ciro daga hoton (b).

Yin amfani da Cyst/AuNPs, masu bincike sun sami nasarar haɓaka dandamali mai sauƙi don gano yanayin yanayin methylation da firikwensin da zai iya bambanta DNA na al'ada daga DNA na ciwon daji lokacin amfani da samfuran jini na gaske don gwajin cutar sankarar bargo. Na'urar firikwensin da aka haɓaka ya nuna cewa DNA da aka fitar daga samfuran jini na gaske ya iya saurin gano ƙarancin DNA na ciwon daji (3nM) cikin sauri a cikin marasa lafiya na cutar sankarar bargo a cikin mintuna 15, kuma ya nuna daidaiton 95.3%. Don ƙara sauƙaƙa gwajin samfurin ta hanyar kawar da buƙatar spectrophotometer, an yi amfani da koyon injin don fassara launi na maganin da kuma bambanta tsakanin mutane na yau da kullun da masu ciwon daji ta hanyar amfani da hoton wayar hannu, kuma an iya samun daidaito a 90.0%.

Bayani: DOI: 10.1039/d2ra05725e