I-Pharmacogenomics iyenza ingqondo — ngakho-ke kungani izinkampani zemithi zingayisebenzisi ngempela?
I-Pharmacogenomics (PGx) ifinyelele ekuphikisaneni okungajwayelekile. Ubufakazi besayensi sekukhule, inzuzo kwezokwelapha (nasezomnotho) ayinakuphikwa, kodwa ukwamukelwa kusalele kancane, kuhlelwe ngezingxenye, futhi kungalingani.
Ikakhulukazi ezilingweni zokwelapha, ukuprofayilwa kwe-pharmacogenomic cishe akusebenzisi. Ukuhlola ku-ClinicalTrials.gov kuthole izilingo zokungenelela ezihlobene ne-PGx eziyi-619 kuphela kwezingu-350,728 zizonke (~0.18%), futhi ngaphansi kwesigamu sabo bacacise ngokusobala ukuthi yiziphi izakhi zofuzo ezazihlolwayo, nakuba i-PGx ezilingweni ingenza izinto eziningi ezisebenzisekayo:
Isignali ecacile yokusebenza: ukwehluka okuncane -> indaba ecacile
yokuphendula/ukungaphenduli Izimo ezimbalwa zokuphepha: ukukhomba ama-genotype anengozi ephezulu kusenesikhathi -> ukuncipha kwe-ADR
ezingagwenywa Ukunciphisa ukuphazamiseka kwesilingo: ukuncipha kokuyeka, ukuncipha kwemithi yokusindisa, ukuncipha kwe-"fire drills"
Isu elingcono lomthamo esigabeni sokuqala: i-PGx isiza ukuchaza izimo ezingavamile ze-PK/PD ngaphambi kokuba zibe yizimanga ze-Dose-Limiting
Toxicity Indaba eqinile ekugcineni: amaqembu angaphansi achazwe kusengaphambili -> isu le-label elivikelekile kakhulu kubakhokhi
Eqenjini eliningi lokuthuthukisa, i-PGx isazizwa iyinto eyengeza ubunzima ngaphandle kokwehlisa ingozi ngokusobala: izivivinyo eziningi, ukuhlela okuningi, imibuzo eminingi yokulawula, nezinto eziningi ezingahle ziphume kabi. Lapho izikhathi zicindezelekile futhi ukuhluleka kubiza kakhulu, umuzwa wukwenza izinto zibe lula, hhayi ukwethula enye ingxenye eshukumisayo, noma ngabe leyo ngxenye ibalulekile kwezokwelapha. Yilokho kanye okwenza i-PGx ibe nobunzima ukushintshela kusuka ku-"mbono omuhle" iye ku-"ingqalasizinda ejwayelekile" ekuhlolweni kwezokwelapha.
Imibiko yokuhlangenwe nakho kwodokotela iphinde ibonise ukuthi amaphaneli e-PGx ezohwebo angase angabambi amagene abalulekile angathathwa izinyathelo ngokwezinkombandlela ze-CPIC/FDA/DPWG, kanti afaka izinhlobo ezinobufakazi obuphansi, okwenza kube nzima ukwazi ukuthi yimiphi imiphumela esebenzayo ngempela. Ngisho noma igene elifanele lifakiwe, amaphaneli angase angakwazi njalo ukuthwebula zonke ama-allele angathathwa izinyathelo ngokwezokwelapha (njengezinhlobo zokuguqulwa kwenani lekhophi noma izakhiwo ezixubile), okungaholela ekubekweni kabi kwezinhlobo zabaphuli-michobo kubo bonke abahlanganyeli.
Noma ngabe kuvivinywa i-PGx, kumele kuhambisane nezikhathi ezimfishane zokuhlola: izinhlelo ezifana ne-PREPARE zidinga ukuthi imiphumela ibuyiselwe kungakapheli cishe izinsuku eziyisikhombisa ukuze ihlale ifanele ngokwezokwelapha, kanti ezimweni zangempela ukusebenzisa i-PGx kubandakanya konke kusukela ekukhetheni amagene nasekuhumusheni i-phenotype kuya ekubikeni, loji ye-CDS, nokuhlanganiswa kwe-EHR phakathi kwamathimba amaningi. Eqenjini, ukuguqula idatha yokulandelana kube yizimpawu ezihambisana nemihlahlandlela kuvame ukuncika ezintambo zokusebenza ezikhethekile ze-bioinformatics kanye nengqalasizinda yasendaweni, okubangela ukubambezeleka, izinselelo zokuhumusha, nokwehluka ezindaweni ezahlukene, odokotela njalo bekhomba izikhawu zesikhathi nokuhumusha okunzima kwemiphumela njengezithiyo ezinkulu.
Okumangazayo wukuthi impikiswano eqinile kakhulu ye-pharmacogenomics isivele yaphakanyiswa. Ucwaningo lwe-PREPARE lwabonisa ukuthi i-PGx yokuvikela ngaphambi kwesikhathi inciphisa imiphumela emibi yemithi ebalulekile kwezokwelapha cishe ngo-30%. Lokho akuncane. Lolu hlobo lobukhulu bemiphumela inkampani yemithi ivamise ukubungaza.
Kodwa ucwaningo lwe-PREPARE luphinde lwabonisa ngokuthula ukuthi kungani i-PGx ingakakhuli: i-genotyping ephakathi nendawo, izikhathi zokulinda ezinsukwini eziningi, ukuhlela okuningi, umthwalo omkhulu wokucubungula idatha, namaphaneli angakaze aklanyelwe izilingo zomhlaba wonke ezihamba ngokushesha.
Ngamanye amazwi, isayensi yasebenza. Ukuhlela kwahluleka.
Lapha-ke i-DNA ME ingena khona.
Kwa-DNA ME, sisondela ku-pharmacogenomics ngokusebenzisa i-nanopore sequencing ngesixazululo sesoftware esisebenza kahle futhi esilula, ngoba lo mhlanganiso ekugcineni wenza i-PGx ivumelane nendlela izilingo ezisebenza ngayo ngempela.
Ukuhlelwa kwe-nanopore kukuvumela ukuthi ukhiqize idatha yemfashini eduze nendawo yokuhlolwa esikhundleni sokuthumela amasampula elabhorethri ehlangene. Okubaluleke kakhulu, ukuhlelwa okufundayo okude kunquma ama-pharmacogene abaluleke kakhulu (njenge-CYP2D6) ngaphandle kokuqagela nokuhlukaniswa okungalungile okubhekene nakho ekuhlelweni okufundayo okufushane kwendabuko.
amaphaneli. Kodwa ukuhlelwa kwe-DNA kuyingxenye kuphela yendaba. Ukuvulwa kwangempela kwenzeka ngemuva kokukhiqizwa kwedatha.I-DNA ME iguqula ukufundwa kwedatha eluhlaza kube imiphumela ye-pharmacogenomic ejwayelekile efundeka ngomshini futhi ilungele ukuhlolwa, ngaphandle kwesidingo kochwepheshe be-bioinformatics ukufinyelela emiphumeleni yokulandelana. Idatha ingafakwa ngqo ekuqapheni ukuphepha, emigomeni yokunyusa umthamo womuthi, noma kumgomo wokuhlola ohlengahlengiswayo. Ukuhlaziywa kungaqhutshwa futhi endaweni yakini ku-laptop eyisisekelo; akudingeki ama-GPU noma imishini yokubala ebizayo, futhi kungadingeki ukulayisha noma ukuthumela idatha yofuzo yomhlanganyeli ebucayi.
Uhlelo lokusebenza lwe-DNA ME olusekelwe ku-nanopore lungabona futhi i-CpG methylation kanye ne-allele-specific methylation ngqo ekugijimeni okukodwa kokulandelana, lufake ungqimba lomsebenzi ekwakhiweni kwephrofayili ye-pharmacogenomic ngaphandle kokuhlolwa okwengeziwe noma ukucubungula okulandelayo. Lokhu kuvumela ukuhlonza ababambiqhaza abangase babe nokuguquguquka ekusebenziseni kwabo imishanguzo empilweni yangempela uma kuqhathaniswa ne-genotype yabo ebilindelwe ngenxa yokulawulwa kwe-epigenetic kwama-pharmacogene, kusiza ukunciphisa ukwehluka kokuchayeka nokuthuthukisa ukuklasifikwa kwabaguquli bemishanguzo ngaphakathi kwenqubo efanayo elula.
Lapho i-PGx iba shesha, ibiza kancane, futhi ingabonakali ekusebenzeni (ifakwe ngendlela efanayo nokuhlolwa kwe-PK noma amalayibhu okuphepha), imboni yezemithi iyeka ukubuza ukuthi kuyafaneleka yini ukukwenza. Umbuzo usiba ukuthi kungani bengamukela ingozi yokungayenzi.
Uma uke wazama ukuhlanganisa i-PGx ekuhlolweni, yini eyayivimba kakhulu: izindleko, isikhathi sokuphendula, ukusebenza, noma ukwamukelwa ngaphakathi?
Sifuna ukwazi ukuthi amaqembu abona ini emhlabeni wangempela.
(Futhi uma ufuna iphaneli esilungele ukuhlolwa + uhlelo lokusebenza lwe-nanopore olusebenza ngokushesha olwenziwe ngokwezinto zakho, sithumele umlayezo ku-DNA ME futhi sizolwakha nawe.)