Opservaciona studija o potencijalnom mehanizmu delovanja SiNi praha u lečenju ulceroznog kolitisa zasnovana na farmakologiji mreže i mašinskom učenju
Sažetak
Uvod/Cilj. Hronični idiopatski ulcerozni kolitis (UK) oštećuje i remeti crevnu mukozu. Dijagnostikovanje UK-a i uspostavljanje diferencijalne dijagnoze je teško. Antiinflamacijska i imunosupresivna svojstva SiNi praha (SNP) čine ga popularnim tretmanom za inflamacijske bolesti. Višestruki mehanizam delovanja SNP-a u lečenju UK-a nije poznat. Cilj rada bio je da se ispitaju potencijalni mehanizmi delovanja SNP-a u lečenju UK-a primenom pristupa farmakologije mreže i mašinskog učenja, identifikuju novi dijagnostički biomarkeri i razvije prediktivni model za dijagnozu UK-a. Metode. Baza podataka i platforma za analizu sistemske tradicionalne kineske medicine (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform – TCMSP) procenila je aktivne sastojke i ciljne proteine. Korišćenjem dva javno dostupna skupa podataka (GSE87473 i GSE75214), sprovedena je diferencijalna analiza matrice ekspresije gena kod UK-a u cilju pronalaženja preklapanja diferencijalno ispoljenih gena i meta delovanja povezanih sa SNP-om. Hub geni procenjeni su korišćenjem nekoliko algoritama mašinskog učenja da bi se kreirao model predikcije. Studije analize na nivou pojedinačnih ćelija korišćene su za identifikaciju gena i imunskih ćelija. NetworkAnalyst je predvideo ushodne transkripcione faktore,mikro˗ribonukleinske kiseline i mrežu protein-jedinjenja. Rezultati. Prema TCMSP bazi podataka, SNP je uklјučivao 95 aktivnih sastojaka i 795 povezanih meta delovanja protiv UK-a. Nakon identifikovanja 79 gena koji se preklapaju, mašinsko učenje je otkrilo pet hub gena: TRPV1, ABCG2, BACE2, MMP3 i LIPC. Provera dijagnostike je izvršena korišćenjem eksternih skupova podataka. Ovi geni su korišćeni za kreiranje prediktivnog modela sa velikom površinom ispod krive [area under the curve (AUC) = 1.000] i skupa podataka za eksternu validaciju sa 1.000 AUC, demonstrirajući odličnu tačnost prediktivnog modela i hub gena. Zaključak. SNP i UK su povezani, a utvrđeni su hub geni za procenu rizika od UK-a. Ova računarska tehnika otvara nove puteve za istraživanje biomarkera UK-a i ciljeva terapijskog delovanja, iako je potrebna dalјa eksperimentalna provera da bi se potvrdili i validirali ovi rezultati.
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