Additional file 2: Figure S1. of Connectivity, not region-intrinsic properties, predicts regional vulnerability to progressive tau pathology in mouse models of disease

Per study r-value chart and scatterplots for connectivity, gene expression profile, and spatial proximity with reported seed regions. (a) Bar chart of r-values, per study, between regional tauopathy data and proximity with the reported seed region in connectivity, gene expression profile, and spatial distance networks. We also show scatterplots of the relationship between proximity with the reported seed region across each network, as indicated by the title above each scatterplot, and regional tau pathology data from (b) DSAD homogenate injected P301S mice and (c) CBD homogenate injected P301S mice from [4], (d) P301S mice injected in the hippocampus and (e) caudoputamen with synthetic tau fibrils from [19], as well as hTau Alz17 mice injected with P301S purified tau tangles in the hippocampus from [9]. Figure S2. Per study r-value chart and scatterplots of regionally summed gene expression across tau aggregation and transcription promoting genes, as well as noradrenergic neurotransmission related genes. (a) Bar chart of r-values for connectivity proximity with reported seed regions, empirical seed regions, and the regionally summed gene expression values with regional tau pathology data. We also show the scatterplots depicting the relationship between the regionally summed gene expression levels with data from (b) DSAD homogenate injected P301S mice and (c) CBD homogenate injected P301S mice from [4], (d) P301S mice injected in the hippocampus and (e) caudoputamen with synthetic tau fibrils from [19], as well as hTau Alz17 mice injected with P301S purified tau tangles in the hippocampus from [9]. Figure S3. Scatterplots and βt curves for each of the relationships between ND modeling using connectivity, gene expression profile similarity, and spatial distance networks with regional tau pathology data, run from reported seedpoints using only study selected regions. The panels are the βt curves for end state tau deposition and regional slope of tauopathy increase, in that order, as well as the scatterplots for end state tau deposition on the top and regional slope of tauopathy increase on the bottom. They are presented in the following order according to study: (b) DSAD homogenate injected P301S mice and (c) CBD homogenate injected P301S mice from [4], (d) P301S mice injected in the hippocampus and (e) caudoputamen with synthetic tau fibrils from [19], as well as hTau Alz17 mice injected with P301S purified tau tangles in the hippocampus from [9]. Figure S4. Scatterplots and βt curves for each of the relationships between ND modeling using connectivity, gene expression profile similarity, and spatial distance networks with regional tau pathology data, run from reported seedpoints using all 426 ABA regions. The panels are the βt curves for end state tau deposition and regional slope of tauopathy increase, in that order, as well as the scatterplots for end state tau deposition on the top and regional slope of tauopathy increase on the bottom. They are presented in the following order according to study: (b) DSAD homogenate injected P301S mice and (c) CBD homogenate injected P301S mice from [4], (d) P301S mice injected in the hippocampus and (e) caudoputamen with synthetic tau fibrils from [19], as well as hTau Alz17 mice injected with P301S purified tau tangles in the hippocampus from [9]. Figure S5. Scatterplots for the correlation between data from the non-seeded mouse dataset obtained from [17], with ND modeling across networks and timepoints as well as regionally summed gene expression with final measured timepoint of regional tauopathy severity; analysis here is done using both only study selected regions and all 426 ABA regions. (a) The beta-t parameter optimization curves at 4 months, 6 months, and 8 months using ND modeling with connectivity and gene expression networks, with analysis done using only study selected regions. (b) The attendant scatterplots related to the beta-t parameter curves above at the final (8 month) timepoint. (c) Scatterplot of regional expression of specific tau and noradrenergic related gene sets with regional tau pathology, using only study selected regions in the analysis. (d) The beta-t parameters optimization curves at 4 months, 6 months, and 8 months using ND modeling with connectivity and gene expression networks, with analysis done using all 426 ABA regions. (e) The attendant scatterplots using the curves for the final (8 month) timepoint. (f) Scatterplot of regional expression of specific tau and noradrenergic related gene sets with regional tau pathology, using all 426 ABA regions in the analysis. (PDF 1.14 mb)