Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis

Abstract Non-alcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide. Its advanced form, non-alcoholic steatohepatitis (NASH), is a major cause of liver fibrosis, but there are no non-invasive tests for diagnosing or preventing it. In our study, we analyzed data from multiple sou...

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Main Authors: Jiahui Feng, Zheng Gong, Jialing Yang, Yuting Mo, Fengqian Song
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97670-4
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author Jiahui Feng
Zheng Gong
Jialing Yang
Yuting Mo
Fengqian Song
author_facet Jiahui Feng
Zheng Gong
Jialing Yang
Yuting Mo
Fengqian Song
author_sort Jiahui Feng
collection DOAJ
description Abstract Non-alcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide. Its advanced form, non-alcoholic steatohepatitis (NASH), is a major cause of liver fibrosis, but there are no non-invasive tests for diagnosing or preventing it. In our study, we analyzed data from multiple sources to find crucial genes linked to NASH fibrosis. We built diagnostic models using 103 machine learning algorithms and validated them with two external datasets. All models performed well, with the best one (RF + Enet[alpha = 0.6]) achieving an average AUC of 0.822. This model used five key genes: LUM, COL1A2, THBS2, COL5A2, and NTS. Our findings show that these genes are important in collagen and extracellular matrix pathways, shedding light on how NASH progresses to liver fibrosis. We also found that certain immune cells, like M1 macrophages, are involved in this process. This study provides a reliable diagnostic tool for assessing fibrosis risk in NASH patients and suggests potential for immunotherapy, laying a foundation for future treatments.
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spelling doaj-art-be9870e39606483e8bec5f40899cd79b2025-08-20T02:28:03ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-97670-4Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosisJiahui Feng0Zheng Gong1Jialing Yang2Yuting Mo3Fengqian Song4Department of Gastroenterology, Loudi Central HospitalDepartment of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologySchool of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Geriatrics, Zhongnan Hospital of Wuhan UniversityDepartment of Gastroenterology, Loudi Central HospitalAbstract Non-alcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide. Its advanced form, non-alcoholic steatohepatitis (NASH), is a major cause of liver fibrosis, but there are no non-invasive tests for diagnosing or preventing it. In our study, we analyzed data from multiple sources to find crucial genes linked to NASH fibrosis. We built diagnostic models using 103 machine learning algorithms and validated them with two external datasets. All models performed well, with the best one (RF + Enet[alpha = 0.6]) achieving an average AUC of 0.822. This model used five key genes: LUM, COL1A2, THBS2, COL5A2, and NTS. Our findings show that these genes are important in collagen and extracellular matrix pathways, shedding light on how NASH progresses to liver fibrosis. We also found that certain immune cells, like M1 macrophages, are involved in this process. This study provides a reliable diagnostic tool for assessing fibrosis risk in NASH patients and suggests potential for immunotherapy, laying a foundation for future treatments.https://doi.org/10.1038/s41598-025-97670-4Machine learningNASHFibrosisBiomarkersImmune microenvironment
spellingShingle Jiahui Feng
Zheng Gong
Jialing Yang
Yuting Mo
Fengqian Song
Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
Scientific Reports
Machine learning
NASH
Fibrosis
Biomarkers
Immune microenvironment
title Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
title_full Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
title_fullStr Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
title_full_unstemmed Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
title_short Machine learning-based integration reveals reliable biomarkers and potential mechanisms of NASH progression to fibrosis
title_sort machine learning based integration reveals reliable biomarkers and potential mechanisms of nash progression to fibrosis
topic Machine learning
NASH
Fibrosis
Biomarkers
Immune microenvironment
url https://doi.org/10.1038/s41598-025-97670-4
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AT jialingyang machinelearningbasedintegrationrevealsreliablebiomarkersandpotentialmechanismsofnashprogressiontofibrosis
AT yutingmo machinelearningbasedintegrationrevealsreliablebiomarkersandpotentialmechanismsofnashprogressiontofibrosis
AT fengqiansong machinelearningbasedintegrationrevealsreliablebiomarkersandpotentialmechanismsofnashprogressiontofibrosis