Additional file 1 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 1: Figure S1. GO terms altered in early PD compared to controls and mitochondrial gene expression patterns (a) Bar charts indicating number of Gene Ontology (GO) terms that are represented in the dataset for each region as determined by Webgestalt and DAVID databases. Top chart shows Biological processes, middle the molecular functions and lower the cellular components. The pie chart adjacent to each chart shows the number of GO terms that overlap or are uniquely represented in the dataset for a region of severe pathology (substantia nigra), mild pathology (parahippocampus) and a region unaffected at Braak stage 3/4 (frontal cortex) as determined by GOview. Colours indicate the level each region is affected at Braak stage 3/4 as determined in Figure 1b. Protein heatmaps from (b) first mass spectrometry run and (c) second mass spectrometry run from IPA showing the level of expression change per protein in the Mitochondrial Dysfunction pathway across each brain region in Braak stage 3/4 compared to controls. Red indicated upregulation and green indicated downregulation compared to controls. Intensity of colour shows level of expression change with deeper colour indicating higher up- or down- regulation

Additional file 5 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 5:Table S2. Biological processes represented across brain regions for early PD cases compared to controls. Shaded box reflects  GO term represented in that brain region

Additional file 8 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 8: Table S5. Comparison of candidate proteins to cell type transcriptomic and proteomic data. Each protein that was compared to downloaded datasets from the articles listed to determine which cell type they associated with. * indicates < 5% FDR significant association in enrichment analysis

Additional file 2 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 2: Figure S2. Candidates for validation workflow A pie chart showing the proportion of mitochondrial proteins out of the total proteins that were detected. The box outlines the method used to select candidate proteins for validation. The final pie chart shows the proportion of mitochondrial proteins within the list of proteins that were selected for validation

Additional file 9 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional File 9: Table S6. Proteins with > 1.5 fold expression change within each region for early PD compared to controls. Protein ID is shown for each protein in the list. Red shading indicates upregulation and green shading indicates downregulation. Each region is highlighted to show the severity of pathology present in that region at Braak stage 3/4 with deepest severely affected > moderately affected > mildly affected > not affected

Additional file 3 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 3: Figure S3. Citrate synthase protein levels across the brain. Graph highlighting how much citrate synthase protein was detected per disease group and brain region. Two-way ANOVA with Sidak’s multiple comparisons determined that citrate synthase levels across disease groups were non-significant (p = 0.1647) whilst those between regions were significant (p < 0.0001). Figure and analysis made with GraphPad Prism 9.02

Additional file 11 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 11: Table S8. List of GO terms represented between early and late PD cases in putamen. Biological processes, molecular functions and cellular components are split into different columns. Top 30 GO terms that overlap between both sets of brains compared to controls are given as well as those only found in early PD and only found in late PD

Additional file 10 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 10: Table S7. List of GO terms represented between early and late PD cases in the frontal cortex. Biological processes, molecular functions and cellular components are split into different columns. Top 30 GO terms that overlap between both sets of brains compared to controls are given as well as those only found in early PD and only found in late PD

Additional file 7 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 7:Table S4. Cellular components represented across brain regions for early PD cases compared to controls Shaded box reflects GO term represented in that brain region

Additional file 6 of Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s

Additional file 6:Table S3. Molecular functions represented across brain regions for early PD cases compared to controls. Shaded box reflects GO term represented in that brain region