Gwajin methylation na DNA tare da wayoyin komai da ruwanka don tantance ciwace-ciwacen da wuri da kuma gwajin cutar sankarar jini tare da daidaito na kashi 90.0%!

Gano cutar kansa da wuri ta hanyar amfani da na'urar daukar hoton ruwa (blood biopsy) sabuwar hanya ce ta gano cutar kansa da kuma gano ta da Cibiyar Kula da Ciwon Daji ta Amurka ta gabatar a cikin 'yan shekarun nan, da nufin gano cutar kansa da wuri ko ma raunuka kafin ta kamu da cutar. An yi amfani da ita sosai a matsayin sabuwar alama don gano cutar kansa da wuri, ciki har da cutar kansar huhu, ciwon gastrointestinal, gliomas da ciwon daji na mata.

Fitowar dandamali don gano alamun methylation landscape (Methylscape) yana da yuwuwar inganta gwajin farko na cutar kansa, wanda hakan zai sanya marasa lafiya a matakin farko da za a iya magancewa.

Kwanan nan, masu bincike sun ƙirƙiro wani dandamali mai sauƙi da kai tsaye don gano yanayin ƙasa na methylation bisa ga ƙwayoyin halittar zinare masu ado da cysteamine (Cyst/AuNPs) tare da na'urar gano ƙwayoyin cuta ta wayar hannu wacce ke ba da damar yin gwajin ƙwayoyin cuta da wuri cikin sauri. Ana iya yin gwajin cutar sankarar bargo cikin mintuna 15 bayan cire DNA daga samfurin jini, tare da daidaito na 90.0%. Taken labarin shine Gano DNA na ciwon daji cikin sauri a cikin jinin ɗan adam ta amfani da AuNPs mai rufe cysteamine da wayar hannu mai amfani da na'ura.

Hoto na 1. Za a iya cimma wani dandamali mai sauƙi da sauri don tantance cutar kansa ta hanyar abubuwan da ke cikin Cyst/AuNPs a matakai biyu masu sauƙi.

An nuna wannan a Hoto na 1. Da farko, an yi amfani da ruwan magani don narkar da gutsuttsuran DNA. Daga nan aka ƙara Cyst/AuNPs zuwa ga ruwan magani mai gauraya. DNA na al'ada da na cutarwa suna da halaye daban-daban na methylation, wanda ke haifar da gutsuttsuran DNA tare da tsarin haɗuwa daban-daban. DNA na al'ada yana taruwa a hankali kuma daga ƙarshe yana taruwa Cyst/AuNPs, wanda ke haifar da yanayin Cyst/AuNPs mai canzawa ja, don haka ana iya ganin canjin launi daga ja zuwa shunayya da ido tsirara. Sabanin haka, bayanin methylation na musamman na DNA na ciwon daji yana haifar da samar da manyan gungu na DNA.

An ɗauki hotunan faranti masu rijiyoyi 96 ta amfani da kyamarar wayar salula. An auna DNA na cutar daji ta hanyar wayar salula mai sanye da na'urar koyon injin idan aka kwatanta da hanyoyin da aka yi amfani da su wajen nazarin kwayoyin halitta.

Binciken cutar kansa a cikin samfuran jini na gaske

Domin faɗaɗa amfani da dandamalin ji, masu binciken sun yi amfani da na'urar firikwensin da ta bambanta tsakanin DNA na yau da kullun da na ciwon daji a cikin samfuran jini na gaske. Tsarin methylation a wuraren CpG suna daidaita bayyanar kwayoyin halitta. A kusan dukkan nau'ikan ciwon daji, an lura da canje-canje a cikin methylation na DNA kuma don haka a cikin bayyanar kwayoyin halitta waɗanda ke haɓaka tumorigenesis suna canzawa.

A matsayin misali ga sauran cututtukan daji da ke da alaƙa da methylation na DNA, masu binciken sun yi amfani da samfuran jini daga marasa lafiya da cutar sankarar bargo da kuma kula da lafiya don bincika tasirin yanayin methylation wajen bambance cutar sankarar bargo. Wannan alamar yanayin methylation ba wai kawai ta fi ƙarfin hanyoyin tantance cutar sankarar bargo da ake da su ba, har ma tana nuna yuwuwar faɗaɗawa zuwa gano nau'ikan cutar kansa iri-iri da wuri ta amfani da wannan gwaji mai sauƙi da sauƙi.

An yi nazarin DNA daga samfuran jini daga marasa lafiya 31 da ke fama da cutar sankarar bargo da kuma mutane 12 masu lafiya. Kamar yadda aka nuna a cikin akwatin zane a Hoto na 2a, sha na samfuran ciwon daji (ΔA650/525) ya yi ƙasa da na DNA daga samfuran al'ada. Wannan ya faru ne saboda ƙaruwar hydrophobic wanda ke haifar da tarin DNA na ciwon daji, wanda ya hana tarin Cyst/AuNPs. Sakamakon haka, waɗannan ƙananan ƙwayoyin cuta sun bazu gaba ɗaya a cikin yadudduka na waje na tarin ciwon daji, wanda ya haifar da yaɗuwar Cyst/AuNPs daban-daban da aka shafa akan tarin DNA na al'ada da na ciwon daji. Daga nan aka samar da lanƙwasa na ROC ta hanyar canza iyaka daga mafi ƙarancin ƙimar ΔA650/525 zuwa matsakaicin ƙima.

Hoto na 2.(a) Ƙimar sha na dangin maganin cyst/AuNPs wanda ke nuna kasancewar DNA na al'ada (shuɗi) da ciwon daji (ja) a ƙarƙashin yanayi mafi kyau.

(DA650/525) na zane-zanen akwati; (b) Binciken ROC da kimanta gwaje-gwajen ganewar asali. (c) Ma'aunin rikicewa don gano marasa lafiya na yau da kullun da na ciwon daji. (d) Sanin hankali, takamaiman abu, ƙimar hasashen mai kyau (PPV), ƙimar hasashen mara kyau (NPV) da daidaiton hanyar da aka haɓaka.

Kamar yadda aka nuna a Hoto na 2b, yankin da ke ƙarƙashin lanƙwasa ROC (AUC = 0.9274) da aka samu don firikwensin da aka haɓaka ya nuna babban ji da takamaiman bayani. Kamar yadda za a iya gani daga zane-zanen akwatin, mafi ƙarancin maki da ke wakiltar ƙungiyar DNA ta yau da kullun ba a raba shi da mafi girman maki da ke wakiltar ƙungiyar DNA ta cutar kansa ba; saboda haka, an yi amfani da koma-baya na dabaru don bambance tsakanin ƙungiyoyin al'ada da na cutar kansa. Idan aka ba da saitin masu canji masu zaman kansu, yana ƙiyasta yuwuwar faruwar wani abu, kamar ciwon daji ko ƙungiyar al'ada. Maɓallin da ya dogara da shi yana tsakanin 0 da 1. Saboda haka sakamakon shine yuwuwar. Mun ƙayyade yuwuwar gano cutar kansa (P) bisa ga ΔA650/525 kamar haka.

inda b=5.3533,w1=-6.965. Don rarraba samfurin, yuwuwar ƙasa da 0.5 tana nuna samfurin al'ada, yayin da yuwuwar 0.5 ko sama da haka tana nuna samfurin ciwon daji. Hoto na 2c yana nuna ma'aunin rikice-rikicen da aka samar daga tantancewar giciye-bar-shi kaɗai, wanda aka yi amfani da shi don tabbatar da daidaiton hanyar rarrabuwa. Hoto na 2d ya taƙaita kimantawar gwajin ganewar asali na hanyar, gami da hankali, takamaiman, ƙimar hasashen tabbatacce (PPV) da ƙimar hasashen korau (NPV).

Na'urorin firikwensin halittu masu amfani da wayoyin komai da ruwanka

Don ƙara sauƙaƙa gwajin samfura ba tare da amfani da na'urorin auna haske ba, masu binciken sun yi amfani da fasahar wucin gadi (AI) don fassara launin maganin da kuma bambance tsakanin mutanen da ke fama da cutar kansa. Ganin haka, an yi amfani da hangen nesa na kwamfuta don fassara launin maganin Cyst/AuNPs zuwa DNA na yau da kullun (shuɗi) ko DNA mai cutar kansa (ja) ta amfani da hotunan faranti 96 da aka ɗauka ta kyamarar wayar hannu. Fasahar wucin gadi na iya rage farashi da inganta samun dama wajen fassara launin mafita na nanoparticle, kuma ba tare da amfani da kowace kayan haɗi na wayar salula ba. A ƙarshe, an horar da samfuran koyon injina guda biyu, gami da Random Forest (RF) da Support Vector Machine (SVM) don gina samfuran. duka samfuran RF da SVM sun rarraba samfuran daidai a matsayin masu kyau da marasa kyau tare da daidaito na 90.0%. Wannan yana nuna cewa amfani da fasahar wucin gadi a cikin fasahar biosensing ta wayar hannu abu ne mai yiwuwa.

Hoto na 3.(a) Ajin da aka yi niyya na maganin da aka rubuta yayin shirya samfurin don matakin ɗaukar hoton. (b) Misalin hoton da aka ɗauka yayin matakin ɗaukar hoton. (c) Ƙarfin launin maganin cyst/AuNPs a kowace rijiya ta farantin rijiyoyi 96 da aka cire daga hoton (b).

Ta amfani da Cyst/AuNPs, masu bincike sun yi nasarar ƙirƙirar wani dandamali mai sauƙi na gano yanayin ƙasa na methylation da na'urar firikwensin da ke iya bambanta DNA na yau da kullun daga DNA na ciwon daji lokacin amfani da samfuran jini na gaske don tantance cutar sankarar bargo. Na'urar firikwensin da aka haɓaka ta nuna cewa DNA da aka cire daga samfuran jini na gaske ya sami damar gano ƙananan adadin DNA na ciwon daji (3nM) cikin sauri da farashi mai kyau a cikin marasa lafiya da cutar sankarar bargo cikin mintuna 15, kuma ya nuna daidaito na 95.3%. Don ƙara sauƙaƙe gwajin samfurin ta hanyar kawar da buƙatar na'urar auna haske, an yi amfani da koyo ta hanyar na'ura don fassara launin maganin da bambance tsakanin mutanen da ke da cutar kansa da waɗanda ke da cutar kansa ta amfani da hoton wayar hannu, kuma an sami damar cimma daidaito a kashi 90.0%.

Nassoshi: DOI: 10.1039/d2ra05725e