Identification of hub genes and pathways in mouse with cold exposure

Xu Wang; Hongbo Hu; Ying Zhang

doi:10.1515/fzm-2024-0023

Identification of hub genes and pathways in mouse with cold exposure

doi: 10.1515/fzm-2024-0023

Xu Wang^{1, 2},
Hongbo Hu³,
Ying Zhang^{1, 2
, ,}

1.
Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China
2.
The State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), and the Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin 150081, China
3.
Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

Funds: Not applicable

More Information

Corresponding author: Ying Zhang, E-mail: zhangying@hrbmu.edu.cn

摘要

Abstract: Background Cold exposure is linked to numerous diseases, yet the changes in key genes and pathways in mice under cold exposure remain unexplored. Understanding these alterations could offer insights into the mechanisms of cold resistance and contribute valuable ideas for treating cold-related diseases. Methods The dataset GSE148361 was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on DEGs. The STRING (Search Tool for the Retrieval of Interacting Genes) database was used to construct a protein-protein interaction (PPI) network. Additionally, gene set enrichment analysis (GSEA) was conducted to identify pathways associated with key genes. miRNAs and upstream transcription factors (TFs) were predicted using the miRNet database. Results A total of 208 DEGs were identified, with 137 upregulated and 71 downregulated. In biological processes, DEGs were enriched in nucleotide and purine-containing compound metabolism. For cellular components, DEGs were involved in condensed chromosomes and mitochondrial protein complexes. In molecular functions, proton transmembrane transporter activity was enriched. KEGG pathway analysis showed significant enrichment in biosynthesis of unsaturated fatty acids, fatty acids, and pyruvate metabolism. From the PPI network, 12 hub genes were identified using MCODE. Four hub genes (Col3a1, fi203, Rtp4, Vcan) demonstrated similar trends in a validation set (GSE110420) and were significantly differentially expressed. GSEA analysis indicated that these four genes were enriched in pathways such as ECM-receptor interaction and cytokinecytokine receptor interaction. The hub gene network included 93 miRNAs and one TF. Conclusion This study identified four hub genes as potential diagnostic biomarkers for cold exposure, providing insights for further research on the effects of cold on gene expression and disease.
- cold exposure /
- hub genes /
- pathway /
- adipose tissue

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Figure 1. Differential expressed genes identified using LIMMA R package in epididymal white adipose tissue samples between cold exposure and normal conditions with the data set GSE148361

(A) Volcano plot of the differential expressed genes, with blue and red colors representing downregulated and upregulated genes, respectively. (B) Heatmap for the top 10 upregulated genes and top 10 downregulated genes as sorted by adjusted p-value. LIMMA: a library for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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Figure 2. Enrichment analysis of differentially expressed metabolism-related genes

(A) biological process (BP) GO enrichment of differentially expressed genes (DEGs). (B) BP GO enrichment of DEGs. (C) molecular functions (MF) GO enrichment of DEGs. (D) KEGG enrichment of DEGs.

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Figure 3. Diagram illustrating the protein-protein interaction (PPI) network of DEGs

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Figure 4. MCODE identifies hub genes and their expression

(A) MCODE network diagram of hub genes from core module analyzed using MCODE. (B) Differential expression of hub genes in GSE45642.

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Figure 5. The expression of hub genes

Differential expression of Hub genes between two groups in external validation set GSE110420.

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Figure 6. Gene set enrichment analysis (GSEA) of hub genes

(A) GSEA pathways of Col3a1. (B) GSEA pathways of Ifi203. (C) GSEA pathways of Rtp4. (D) GSEA pathways of Vcan.

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Figure 7. Construction of the miRNA-gene-transcription factor regulatory network

Transcription factors (TFs) are represented by green color, miRNAs by bule, and hub genes by red.

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