Integrating machine learning algorithms and single-cell analysis to identify gut microbiota-related macrophage biomarkers in atherosclerotic plaques

作者全名：Ke, Yin; Yue, Jian; He, Jiaming; Liu, Guojing

作者地址：[Ke, Yin; Liu, Guojing] Chongqing Med Univ, Dept Neurosurg, Univ Town Hosp, Chongqing, Peoples R China; [Ke, Yin] Maternal & Child Hlth Hosp Yong Chuan, Dept Nursing, Chongqing, Peoples R China; [Yue, Jian] Gaozhou Peoples Hosp, Dept Breast Surg, Gaozhou, Peoples R China; [He, Jiaming] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China

通信作者：Liu, GJ (通讯作者)，Chongqing Med Univ, Dept Neurosurg, Univ Town Hosp, Chongqing, Peoples R China.

来源：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001214613900001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：gut microbiota; macrophage; machine learning; atherosclerotic plaques; bioinformatics

摘要：Objective The relationship between macrophages and the gut microbiota in patients with atherosclerosis remains poorly defined, and effective biological markers are lacking. This study aims to elucidate the interplay between gut microbial communities and macrophages, and to identify biomarkers associated with the destabilization of atherosclerotic plaques. The goal is to enhance our understanding of the underlying molecular pathways and to pave new avenues for diagnostic approaches and therapeutic strategies in the disease.Methods This study employed Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis on atherosclerosis datasets to identify macrophage-associated genes and quantify the correlation between these genes and gut microbiota gene sets. The Random Forest algorithm was utilized to pinpoint PLEK, IRF8, BTK, CCR1, and CD68 as gut microbiota-related macrophage genes, and a nomogram was constructed. Based on the top five genes, a Non-negative Matrix Factorization (NMF) algorithm was applied to construct gut microbiota-related macrophage clusters and analyze their potential biological alterations. Subsequent single-cell analyses were conducted to observe the expression patterns of the top five genes and the interactions between immune cells. Finally, the expression profiles of key molecules were validated using clinical samples from atherosclerosis patients.Results Utilizing the Random Forest algorithm, we ultimately identified PLEK, IRF8, CD68, CCR1, and BTK as gut microbiota-associated macrophage genes that are upregulated in atherosclerotic plaques. A nomogram based on the expression of these five genes was constructed for use as an auxiliary tool in clinical diagnosis. Single-cell analysis confirmed the specific expression of gut microbiota-associated macrophage genes in macrophages. Clinical samples substantiated the high expression of PLEK in unstable atherosclerotic plaques.Conclusion Gut microbiota-associated macrophage genes (PLEK, IRF8, CD68, CCR1, and BTK) may be implicated in the pathogenesis of atherosclerotic plaques and could serve as diagnostic markers to aid patients with atherosclerosis.

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