2.5. Functional enrichment and bioinformatics analysis

The Metascape^[29] (http://metascape.org) online database integrates over forty bioinformatics knowledge bases enabling the extraction of abundant annotations, as well as the identification of enriched pathways and the construction of protein–protein interaction networks from lists of gene and protein identifiers. Using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) tools within Metascape, we analyzed a genes list containing DEGs genes to further explore the biological process of disease. The GO analysis included three categories: biological process (BP), cellular component, and molecular function. We undertook enrichment analysis of DEGs different comparison groups. Protein–protein interaction (PPI) analysis was carried out to predict the interaction of selected genes based on the STRING Database (V.11).^[30] Further, Molecular Complex Detection (MCODE) algorithm was used to check modules of the PPI network.^[31] KEGG pathway and GO terms with computed P values ˂ 0.05, were considered significantly enriched based on the hypergeometric distribution.