Single-cell Sequencing Combined with Machine Learning Algorithms Reveals Cell-cell Communication and Key Regulatory Genes in Patients with Heart Failure
WANG Xuefu
RAO Jin
ZHANG Li
LIU Xuwen
ZHANG Yufeng
Abstract：Objective:To construct a diagnostic model for heart failure(HF)based on single-cell sequencing and machine learning algorithms,and explore cell-cell communication in HF patients.Methods:The Seurat package was used for quality control,dimensionality reduction,clustering,and annotation of single-cell transcriptome(scRNA-seq)data.The immune activity of each cell subset was evaluated using AUCell,and the cell subset with the highest immune activity was selected for further analysis.Differential expression genes were screened using the limma package based on bulk transcriptome(Bulk RNA-seq)data,and gene set enrichment analysis(GSEA)was performed.Furthermore,disease classification was used as the response variable and differential genes as the explanatory variables to select macrophage-related feature genes with diagnostic value through four machine learning models.The diagnostic ability of key genes was evaluated using receiver operating characteristic(ROC)curves.Bar plots were also constructed to predict the overall risk score of HF occurrence.Finally,CellChat was used to explore cell-cell interactions between cell subtypes.Results:Compared to normal samples,the proportion of macrophages in HF patients was higher,and macrophages had the highest immune activity score.Gene enrichment analysis of macrophage subtypes showed significant enrichment of leukocyte-mediated immune processes and antigen processing and presentation.The intersection of multiple machine learning algorithms revealed that SERPINA3,GPAT3,ANPEP,and FCGBP could serve as feature genes and were closely related to macrophages.Receiver operator characteristic(ROC)curves demonstrated that our diagnostic model had good predictive ability.Cell communication analysis revealed complex outgoing and incoming dynamics in the signaling pathways between fibroblast-macrophage mediated-neutrophil mediated by MIF and macrophages--neutrophils mediated by ANNEXIN.Conclusion:The four key genes serve as biomarkers and have good diagnostic value.Macrophage-mediated immune processes and cell-cell communication play a crucial role in the immune microenvironment of HF.
Keywords：heart failuresingle cell sequencingmachine learningdiagnostic modelscell communication
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：14( 525-538 )