Multi-omics and machine learning-driven identification of PTM-related potential biomarkers and therapeutic insights in MASLD
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is biologically heterogeneous and lacks sufficiently validated molecular biomarkers for disease characterization. Post-translational modification (PTM)-related genes may link metabolic stress to lipid dysregulation and inflammation, but their relevance remains unclear. We integrated liver transcriptomic datasets and PTM-related gene annotation with machine-learning prioritization, cell-resolved analysis, and experimental validation. PELI1, VPS41, and TRIM32 were prioritized as potential diagnostic candidates based on their disease-associated expression and discriminative performance in the examined transcriptomic cohorts, with concordant expression changes observed in an independent local liver cohort. Single-nucleus RNA sequencing suggested that disease-associated VPS41 upregulation was most prominent in hepatocytes. VPS41 expression also increased in livers from a diet-induced mouse model of MASLD and in lipid-loaded hepatocytes. In primary mouse hepatocytes, Vps41 knockdown aggravated lipid accumulation, lipogenic gene expression, and inflammatory responses, whereas VPS41 overexpression attenuated these changes. These findings distinguish the expression-based evidence supporting the diagnostic potential of PELI1 and TRIM32 from the functional evidence for VPS41 and support a protective role for VPS41 under hepatocellular lipid stress. Prospective clinical validation and in vivo gain- and loss-of-function studies are required to establish diagnostic utility and the causal and therapeutic relevance of VPS41.
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BibTeX
@article{yao2026multiomics,
title = {{Multi-omics and machine learning-driven identification of PTM-related potential biomarkers and therapeutic insights in MASLD}},
author = {Qingrong Yao and Xuan Zhong and Jiawei Chen and Wenbin An and Jiamian Wang and Hong Tang and Zhenyu Liu and Jiajia Chen and Lina Zhao and Sha Li and Liying Shi and Bei Zhang},
journal = {Scientific Reports},
year = {2026},
month = sep,
doi = {10.1038/s41598-026-72903-2},
url = {https://www.nature.com/articles/s41598-026-72903-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-omics and machine learning-driven identification of PTM-related potential biomarkers and therapeutic insights in MASLD
AU - Qingrong Yao
AU - Xuan Zhong
AU - Jiawei Chen
AU - Wenbin An
AU - Jiamian Wang
AU - Hong Tang
AU - Zhenyu Liu
AU - Jiajia Chen
AU - Lina Zhao
AU - Sha Li
AU - Liying Shi
AU - Bei Zhang
PY - 2026
DA - 2026/09/30
JO - Scientific Reports
DO - 10.1038/s41598-026-72903-2
UR - https://www.nature.com/articles/s41598-026-72903-2
AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) is biologically heterogeneous and lacks sufficiently validated molecular biomarkers for disease characterization. Post-translational modification (PTM)-related genes may link metabolic stress to lipid dysregulation and inflammation, but their relevance remains unclear. We integrated liver transcriptomic datasets and PTM-related gene annotation with machine-learning prioritization, cell-resolved analysis, and experimental validation. PELI1, VPS41, and TRIM32 were prioritized as potential diagnostic candidates based on their disease-associated expression and discriminative performance in the examined transcriptomic cohorts, with concordant expression changes observed in an independent local liver cohort. Single-nucleus RNA sequencing suggested that disease-associated VPS41 upregulation was most prominent in hepatocytes. VPS41 expression also increased in livers from a diet-induced mouse model of MASLD and in lipid-loaded hepatocytes. In primary mouse hepatocytes, Vps41 knockdown aggravated lipid accumulation, lipogenic gene expression, and inflammatory responses, whereas VPS41 overexpression attenuated these changes. These findings distinguish the expression-based evidence supporting the diagnostic potential of PELI1 and TRIM32 from the functional evidence for VPS41 and support a protective role for VPS41 under hepatocellular lipid stress. Prospective clinical validation and in vivo gain- and loss-of-function studies are required to establish diagnostic utility and the causal and therapeutic relevance of VPS41.
SN - 2045-2322
ER -