Research Paper Volume 15, Issue 24 pp 15451—15472
Identification and validation of key biomarkers associated with macrophages in nonalcoholic fatty liver disease based on hdWGCNA and machine learning
- 1 Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
- 2 School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Received: August 19, 2023 Accepted: November 21, 2023 Published: December 21, 2023
https://doi.org/10.18632/aging.205374How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: NAFLD has attracted increasing attention because of its high prevalence and risk of progression to cirrhosis or even hepatocellular carcinoma. Therefore, research into the root causes and molecular indicators of NAFLD is crucial.
Methods: We analyzed scRNA-seq data and RNA-seq data from normal and NAFLD liver samples. We utilized hdWGCNA to find module-related genes associated with the phenotype. Multiple machine learning algorithms were used to validate the model diagnostics and further screen for genes that are characteristic of NAFLD. The NAFLD mouse model was constructed using the MCD diet to validate the diagnostic effect of the genes.
Results: We identified a specific macrophage population called NASH-macrophages by single-cell sequencing analysis. Cell communication analysis and Pseudo-time trajectory analysis revealed the specific role and temporal distribution of NASH-macrophages in NAFLD. The hdWGCNA screening yielded 30 genes associated with NASH-macrophages, and machine learning algorithms screened and obtained two genes characterizing NAFLD. The immune infiltration indicated that these genes were highly associated with macrophages. Notably, we verified by RT-qPCR, IHC, and WB that MAFB and CX3CR1 are highly expressed in the MCD mouse model and may play important roles.
Conclusions: Our study revealed a macrophage population that is closely associated with NAFLD. Using hdWGCNA analysis and multiple machine learning algorithms, we identified two NAFLD signature genes that are highly correlated with macrophages. Our findings may provide potential feature markers and therapeutic targets for NAFLD.