Functional Enrichment and Protein–Protein Interaction Analysis

The Database for Annotation, Visualization, and Integrated Discovery (DAVID; http://david.ncifcrf.gov) (12) is an online biological information database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) is a database resource for understanding high-level functions and biological systems from large-scale molecular datasets generated using high-throughput experimental technologies (13). Gene Ontology (GO) is a major bioinformatics tool for annotating genes and analyzing their biological processes (14). DAVID 6.8 Bioinformatics Resources was used for pathway annotations. Statistical significance was set at P < 0.05. A PPI network was established using the STRING (version 10.0) (15) online search tool, and an interaction with a combined score >0.4 was considered statistically significant. The PPI network was visualized using Cytoscape (version 3.7.2).