Differentially expressed genes were sorted and filtered with a cutoff of absolute log2 FC>±0.5, FDR<0.05 and differentially expressed total proteins and phosphopeptides were sorted and filtered for p values<0.05. The filtered differentially expressed genes, proteins, and phosphorylated proteins were submitted to String-db (https://string-db.org/) and were filtered with an edge confidence of 0.9 and for at least one interaction. Although several proteins had multiple phosphopeptide abundance changes, only the unique UniProt accession numbers were submitted to String-db from the filtered phosphopeptide list. Using String-db, gene ontology (GO), KEGG and Reactome pathway enrichment were determined for these filtered differentially expressed genes, proteins, and phosphorylated proteins. The filtered differentially expressed genes and global proteins were then analyzed in CytoScape software using the cytoHubba plugin to identify hub genes/proteins (nodes ≥ 7 degrees) (Chin et al. 2014). Hubs were categorized by number of degrees and maximal clique centrality (MCC) which is another validated predictor of how essential a particular node is within a network (Chin et al. 2014). Full network and enrichment results analyses may be found in the Supplementary Files.
