Of the 345 unique proteins that were submitted for interaction analysis in String-db, 221 edges were discovered versus an expected number of 96 edges (Figure 4; enrichment p < 1×10–16). The assessment of enriched GO and pathways revealed 532 BP, 91 MF, 190 CC, 20 KEGG pathways, and 26 Reactome pathways enriched in the network of proteins with differentially expressed phosphopeptides (See Supplementary File “Enrichment_Phospho” for full details on significantly enriched GO terms for network of differentially expressed phosphorylated proteins). In particular, the synapse CCs (highlighted in green, Figure 4) and the neuronal system, transmission across chemical synapses, trafficking of AMPA receptors, and clathrin-mediated endocytosis Reactome pathways were particularly prominent in this network of differential phosphorylated proteins. Additionally, cellular organization and cytoskeleton-related BPs and MFs such as cellular component organization and cytoskeletal protein binding were strongly enriched. Similarly, microtubule-associated protein 1B, ankyrin-2, neurofilament heavy polypeptide, and protein piccolo, which are critical structural and scaffolding proteins located in the synapse, demonstrated twelve or more unique phosphopeptides that were each found to be differentially expressed between lines (Table 6).
