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Its advanced form, metabolic dysfunction associated steatohepatitis (MASH), includes liver ballooning, and inflammation, and can progress to cirrhosis and hepatocellular carcinoma (HCC). Despite the increasing burden, effective pharmacotherapies for MASLD\/MASH are still lacking. Programmed cell death mechanisms, such as autophagy and ferroptosis, are critical in the pathology of MASLD, influencing liver inflammation, fibrosis, and malignant transformation. This study employed six machine learning models\u2014Random Forest, Logistic Regression, Extra Trees Classifier, Linear Discriminant Analysis, and Light Gradient Boosting Machine\u2014to identify significant drug targets using Febuxostat, Perindopril, Amlodipine, and Atorvastatin, evaluated through molecular, biochemical, immunohistochemical, and pathological markers. We identified genes associated with MASH using microarray datasets from the Gene Expression Omnibus database, followed by protein-protein interaction and functional enrichment analyses to select genes related to ferroptosis, autophagy, and their epigenetic regulators (miRNAs-LncRNAs) in MASH-induced rats. Quantitative real-time PCR validated the expression of selected networks (mRNAs-miRNAs-LncRNAs). Additionally, we measured biochemical, inflammatory, and liver pathology markers to ensure the model\u2019s robustness. Our results identified 16 out of 29 valuable therapeutic targets with an accuracy of 88.74% and an AUC of 0.9745, including LPCAT3, HGS, TSG101, SNF8, rno-miR-27a-5p, rno-miR-329-5p, CTBP1-AS2, ALT, AST, ALP, GGT, D. Bilirubin, Albumin, TMAO, GPX4, and TGF\u03b21.<\/jats:p>","DOI":"10.1007\/s13105-026-01181-3","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:25:37Z","timestamp":1777281937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine learning-based prediction model for drug target identification and MASH improvement: a comprehensive analysis of biochemical and ferroptosis\/autophagy biomarkers"],"prefix":"10.1007","volume":"82","author":[{"given":"Marwa","family":"Matboli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aly","family":"Elanwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa","family":"Khaled","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Khaled","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Hamdy Badr","family":"Eltantawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada Galal","family":"Hamam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar Yehia","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Fouad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Asmaa","family":"Tarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Elmasry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M","family":"El-Shafei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma Emad","family":"Aboulhoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gouda Ibrahim","family":"Diab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim H.","family":"Aboughaleb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"1181_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.02.007","author":"L Miao","year":"2024","unstructured":"Miao L, Targher G, Byrne CD, Cao YY, Zheng MH (2024) Current status and future trends of the global burden of MASLD. 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