Additional file 3: Table S2. of Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation

STRING bioinformatics assessment of all significant changes, including subtle effects. Ranked list of the significant transcript expression changes in PINK1-deficient mouse cerebellar tissue at ages 6 weeks, 6 months, and 18 months, which were used as input for the STRING analysis (A). Significant functional enrichments in the protein-protein-interaction network according to the STRING database is shown regarding GO Cellular component at 6 weeks with all factors of AdjPvalue <0.05 (B), 6 months with all factors of AdjPvalue <0.05 (C), and 18 months with all factors of AdjPvalue <0.01, with the term “intracellular membrane-bounded organelle” being prominent at all 3 ages (D). Prominent enrichments were highlighted in yellow color. In GO Molecular Process at 18 months with all factors of AdjPvalue <0.01 the relevance of stimulus- and stress-dependent pathways is apparent, e.g., endoplasmic reticulum stress, and a significant enrichment of mitophagy factors appears here in lines 495 and 518 (E). Among KEGG pathways at 18 months with all factors of AdjPvalue <0.01, the highest ranked pathways include “MAPK signaling”, “Ubiquitin-mediated proteolysis”, “Protein processing in endoplasmic reticulum” and “Bacterial invasion of epithelial cells” (F). Orange color was used to highlight some MAPK-dependent synaptic signaling pathways with significant enrichment, purple color was used for ubiquitination and protein processing pathways, green color was used for neuroinflammation pathways. (ZIP 366 kb)