Autophagy-Lipid Metabolism-Related Gene Analysis in Diabetic Samples

The study adhered to the data access policies of all the participating databases. A total of 803 autophagy-related genes (Table S1) were compiled from the Human Autophagy Moderator database (HAMdb) and the Human Autophagy Database (HADb). A total of 1,564 genes associated with lipid metabolism were sourced from the MSigDB database (https://www.gsea-msigdb.org/gsea/msigdb/), as detailed in Table S2. A comparative analysis between the diabetic and control samples revealed 10 DEGs whose expressions significantly differed (P < 0.05, |log2-fold change| > 0.5). In the diabetic samples, 8 genes were upregulated, and 2 were downregulated (Table S3). On the basis of the module-trait correlation heatmap (Fig. 2C), genes that clustered in the brown module (n = 189; Table S4) exhibited the strongest positive correlations with autophagy-lipid metabolism (r = 0.4764; P < 0.05). A significant positive correlation (cor = 0.65, P < 0.05) between MM and GS suggests a strong association of the central hub genes in this module with autophagy-lipid metabolism. Intersection analysis revealed five autophagy-lipid metabolism-related DEGs that were shared between the DEGs and module genes (Table S5). GO enrichment analysis revealed significant enrichment in biological processes (BP), such as embryonic organ development (GO:0048568), regulation of cytokine-mediated signalling (GO:0001959), and hindbrain development (GO:0030902). Additionally, molecular functions (MF) terms included calcium-dependent protein kinase C activity (GO:0004698), protein ADP-ribosylase activity (GO:1990404), protein kinase C activity (GO:0004697), and transcription corepressor activity (GO:0003714) (Table S6). KEGG pathway analysis revealed predominant enrichment of viral protein interaction with cytokine and cytokine receptor (has04061), chemokine signaling pathway (has04062), cytokine-cytokine receptor interaction (has04060), human cytomegalovirus infection (has05163), rheumatoid arthritis (has05323), IL-17 signaling pathway (has04657), Chagas disease (has05142), Toll-like receptor signaling pathway (has04620), and TNF signaling pathway (has04668) (Table S7).