2.7 The construction of gene-metabolism-disease network

As fundamental biological processes, metabolism and gene expression work together to maintain homeostasis and to regulate cell growth, survival, and differentiation, which in turn affects the course of disease (Yuan et al., 2013). In order to investigate the relationship between metabolites and aging-related diseases from the transcriptome perspective, we downloaded transcriptome datasets from the Gene Expression Omnibus (GEO) database as shown in Additional file 1: Supplementary Table S6 and the specific information of samples can be found in Additional file 1: Supplementary Table S7. The ‘sva’ package of R was utilized to eliminate batch effects of the datasets. The limma package was used for differential analysis. Genes with p < 0.05, |logFC|>0.3 were considered as differentially expressed genes (DEGs). The results were visualized using the ‘gglot2’ package for R. The Kyoto Encyclopedia of Genes and Genomes (KEGG) is a method that is used to find out the relationship between genes and metabolic pathways (Kanehisa et al., 2023). The STITCH software (http://stitch.embl.de/) is a public accessible database of gene-metabolite correlations. The STITCH website was used to build the interaction network between DEGs and significant metabolites, which was visualized with Cytoscape and Adobe illustrator.