Fig. 3: Adult AS model rats (P84) recapitulate the proteomic alterations observed in AS model mice across different brain regions.

A Schematic representation of experimental design. Control and AS model rats were sacrificed at P84. Pooled tissue of cerebellum (CB), cortex (CX), and hippocampus (HC) of control and AS animals was used to generate a sample-specific spectral library in DDA (data dependent acquisition) mode. Individual samples were further analyzed using data-independent acquisition (DIA) mass spectrometry. B UBE3A raw protein intensity plot of cerebellum (CB), cortex (CX), and hippocampus (HC) of control and AS model rats plotted as percentage of CB control protein levels (mean ± s.e.m.). C Partial least square-discriminant analysis (PLS-DA) performed on the total proteome of control and AS model rats resolved according to brain region (T1 and T2; cerebellum, cortex, hippocampus) and genotype (T3; control and AS), and projected in 3D space. D Venn diagram of statistically significant (adj. p value < 0.05) proteins altered in each brain region in AS model rats. E Heatmap of proteins that pass statistical significance in the cerebellum. Proteins fall into two categories: increased (green cluster) or decreased (blue cluster) levels in AS compared to controls. F–H Volcano plot of p value vs. Log₂ fold change per brain region. Proteins that are statistically significant in each pairwise comparison are highlighted (Blue: CB, Green: HC, Yellow: Cortex). Proteins significant in all three brain regions are marked in black stars. Subset of proteins of interest from Fig. 1E is labeled. I–K Log₂ fold change correlation plots between mouse cortex and rat cortex for proteins in the aminoacyl tRNA synthetases pathway (G), proteasome subunits (H), and synaptic proteins (I) as filtered in Fig. 2F. Correlation coefficients are calculated using Pearson’s method.