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Background: Evidence suggests that hepatocyte mitochondrial dysfunction leads to abnormal lipid metabolism, redox imbalance, and programmed cell death, driving the onset and progression of non-alcoholic steatohepatitis (NASH). Identifying hub mitochondrial genes linked to NASH may unveil potential therapeutic targets.

Methods: Mitochondrial hub genes implicated in NASH were identified via analysis using 134 algorithms.

Results: The Random Forest algorithm (RF), the most effective among the 134 algorithms, identified three genes: Aldo-keto reductase family 1 member B10 (AKR1B10), thymidylate synthase (TYMS), and triggering receptor expressed in myeloid cell 2 (TREM2). They were upregulated and positively associated with genes promoting inflammation, genes involved in lipid synthesis, fibrosis, and nonalcoholic steatohepatitis activity scores in patients with NASH. Moreover, using these three genes, patients with NASH were accurately categorized into cluster 1, exhibiting heightened disease severity, and cluster 2, distinguished by milder disease activity.

Conclusion: These three genes are pivotal mitochondrial genes implicated in NASH progression.

Titel:	Machine learning-based algorithm identifies key mitochondria-related genes in non-alcoholic steatohepatitis.
Autor/in / Beteiligte Person:	Dai, L ; Jiang, R ; Zhan, Z ; Zhang, L ; Qian, Y ; Xu, X ; Yang, W ; Zhang, Z
Link:	Full Text Finder (Volltext)
Zeitschrift:	Lipids in health and disease, Jg. 23 (2024-05-08), Heft 1, S. 137
Veröffentlichung:	[London] : BioMed Central, 2002-, 2024
Medientyp:	academicJournal
ISSN:	1476-511X (electronic)
DOI:	10.1186/s12944-024-02122-z
Schlagwort:	Humans Mitochondria genetics Mitochondria metabolism Lipid Metabolism genetics Aldo-Keto Reductases genetics Aldo-Keto Reductases metabolism Genes, Mitochondrial Non-alcoholic Fatty Liver Disease genetics Non-alcoholic Fatty Liver Disease pathology Machine Learning Algorithms
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Lipids Health Dis] 2024 May 08; Vol. 23 (1), pp. 137. <i>Date of Electronic Publication: </i>2024 May 08. MeSH Terms: Non-alcoholic Fatty Liver Disease* / genetics ; Non-alcoholic Fatty Liver Disease* / pathology ; Machine Learning* ; Algorithms* ; Humans ; Mitochondria / genetics ; Mitochondria / metabolism ; Lipid Metabolism / genetics ; Aldo-Keto Reductases / genetics ; Aldo-Keto Reductases / metabolism ; Genes, Mitochondrial References: J Hepatol. 2023 Feb;78(2):415-429. (PMID: 36209983) ; JAMA. 2020 Mar 24;323(12):1175-1183. (PMID: 32207804) ; Nat Methods. 2015 May;12(5):453-7. (PMID: 25822800) ; Cell. 2020 Jun 11;181(6):1207-1217. (PMID: 32531244) ; Gastroenterology. 2019 Apr;156(5):1264-1281.e4. (PMID: 30660725) ; BMC Bioinformatics. 2008 Dec 29;9:559. (PMID: 19114008) ; Metabolism. 2019 Mar;92:82-97. (PMID: 30502373) ; Trends Endocrinol Metab. 2017 Apr;28(4):250-260. (PMID: 27986466) ; Metabolism. 2016 Aug;65(8):1080-6. (PMID: 26775559) ; Life Sci. 2023 Jan 1;312:121162. (PMID: 36372213) ; J Hepatol. 2019 Mar;70(3):531-544. (PMID: 30414863) ; Hepatology. 2023 Apr 1;77(4):1335-1347. (PMID: 36626630) ; Cell. 2019 May 2;177(4):881-895.e17. (PMID: 31051106) ; Metabolites. 2021 May 21;11(6):. (PMID: 34063865) ; J Exp Clin Cancer Res. 2018 Dec 29;37(1):327. (PMID: 30594216) ; Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):349-364. (PMID: 29740166) ; Trends Endocrinol Metab. 2016 Feb;27(2):84-95. (PMID: 26703097) ; Nucleic Acids Res. 2021 Jan 8;49(D1):D1541-D1547. (PMID: 33174596) ; Nat Rev Gastroenterol Hepatol. 2018 Jan;15(1):11-20. (PMID: 28930295) ; Hepatology. 2013 Oct;58(4):1497-507. (PMID: 23299992) ; mBio. 2023 Feb 28;14(1):e0266322. (PMID: 36715540) ; Nucleic Acids Res. 2018 Jul 2;46(W1):W60-W64. (PMID: 29912392) ; Metabolism. 2021 Apr;117:154708. (PMID: 33444607) ; Eur J Clin Invest. 2022 Mar;52(3):e13622. (PMID: 34050922) ; Mol Metab. 2021 Aug;50:101167. (PMID: 33460786) ; Nucleic Acids Res. 2017 Jan 4;45(D1):D833-D839. (PMID: 27924018) ; Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. (PMID: 21876188) ; Cell Mol Gastroenterol Hepatol. 2022;13(3):879-899. (PMID: 34923175) ; Hepatology. 2021 Mar;73(3):1140-1157. (PMID: 32535965) ; Nat Rev Immunol. 2022 Jul;22(7):429-443. (PMID: 34741169) ; Acta Pharmacol Sin. 2022 May;43(5):1141-1155. (PMID: 35105958) ; Nat Med. 2023 Mar;29(3):562-573. (PMID: 36894650) ; Antioxid Redox Signal. 2022 Jun;36(16-18):1081-1100. (PMID: 35044230) ; Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) ; Nat Rev Gastroenterol Hepatol. 2019 Mar;16(3):145-159. (PMID: 30482910) ; Biochim Biophys Acta Mol Basis Dis. 2022 Apr 1;1868(4):166319. (PMID: 34954342) ; Mol Metab. 2023 Apr;70:101694. (PMID: 36801448) ; Mol Metab. 2017 Dec;6(12):1625-1633. (PMID: 29092796) ; Int J Mol Sci. 2022 Aug 26;23(17):. (PMID: 36077090) ; Annu Rev Pathol. 2016 May 23;11:451-96. (PMID: 26980160) ; J Hepatol. 2018 Sep;69(3):705-717. (PMID: 29705240) ; Gastroenterology. 2016 Jun;150(8):1769-77. (PMID: 26928243) ; Cancer Cell Int. 2022 Jan 29;22(1):47. (PMID: 35093082) ; BMC Bioinformatics. 2013 Jan 16;14:7. (PMID: 23323831) ; J Transl Med. 2023 Jul 28;21(1):510. (PMID: 37507803) ; Hepatol Commun. 2022 Mar;6(3):448-460. (PMID: 34532996) ; Cell. 2012 Mar 16;148(6):1145-59. (PMID: 22424226) ; Redox Biol. 2023 May;61:102643. (PMID: 36857930) ; Gastroenterology. 2018 Sep;155(3):629-647. (PMID: 30012333) ; Nat Commun. 2019 Apr 3;10(1):1523. (PMID: 30944313) ; Sci Transl Med. 2020 Dec 2;12(572):. (PMID: 33268508) ; Nat Med. 2018 Jul;24(7):908-922. (PMID: 29967350) ; J Clin Invest. 2021 Feb 15;131(4):. (PMID: 33586673) ; Lancet. 2021 Jun 5;397(10290):2212-2224. (PMID: 33894145) Grant Information: 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine; 2023zhyx-C20 Research Fund of Anhui Institute of translational medicine Contributed Indexing: Keywords: Machine learning; Mitochondria; NASH Substance Nomenclature: EC 1.1.1.- (Aldo-Keto Reductases) Entry Date(s): Date Created: 20240509 Date Completed: 20240509 Latest Revision: 20240511 Update Code: 20240511 PubMed Central ID: PMC11077862

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Machine learning-based algorithm identifies key mitochondria-related genes in non-alcoholic steatohepatitis.